Current and Future Cancer Chemoprevention Strategies

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: closed (30 May 2022) | Viewed by 38697

Special Issue Editors

Department of Molecular Oncology, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia
Interests: oncology; tumor progression; chemotherapy; inflammation; cellular senescence
Special Issues, Collections and Topics in MDPI journals
Molecular Biology Laboratory, Faculty of Medicine, University of Atacama, Atacama, Chile
Interests: biologia molecular; fisiopatologia
Special Issues, Collections and Topics in MDPI journals
Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK
Interests: cancer metabolism; mTORC1 signaling; glutamine metabolism; hepatocellular carcinoma
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to announce the new Special Issue for Pharmaceutics entitled " Current and future cancer chemoprevention strategies."

The increasing understanding of cancer pathobiology has shown how to develop molecular approaches to treating neoplasm and decreasing mortality rates. These advances have also influenced active chemoprevention development to promote cancer prevention and development, reduce cancer incidence or counter disease progression, and cancer recurrence after surgery.

Chemoprevention includes the use of natural, synthetic, or biological agents with the aim, at a molecular level, to reverse, suppress or prevent either the initial phases of carcinogenesis or the progression of premalignant cells to the invasive disease stage. Understanding chemopreventive agents' molecular mechanisms will shed light on preventing carcinogenesis and new therapeutic strategies’ compounds with potential clinical applications.

This Special Issue on " Current and future cancer chemoprevention strategies " encourages authors to submit their original research or review articles that bring new pieces of evidence or synthesis of the most recent and breakthrough data in the field of cancer chemoprevention. Topics include, but are not limited to: inorganic and organic compounds; nano- compounds; natural compounds; extracts plants; hormonal chemopreventive agent; diet-related agents; medication/pharmacological drugs; repurposing drugs.

Dr. Juan Santibanez
Dr. César A. Echeverría
Dr. Victor Hugo Villar
Guest Editors

Manuscript Submission Information

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Keywords

  • chemoprevention
  • cancer
  • cell death
  • metabolism
  • cell invasion
  • metastasis

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Published Papers (14 papers)

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Research

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38 pages, 11193 KiB  
Article
Design, Synthesis, In Silico Studies and Inhibitory Activity towards Bcr-Abl, BTK and FLT3-ITD of New 2,6,9-Trisubstituted Purine Derivatives as Potential Agents for the Treatment of Leukaemia
by Jeanluc Bertrand, Hana Dostálová, Vladimír Kryštof, Radek Jorda, Thalía Delgado, Alejandro Castro-Alvarez, Jaime Mella, David Cabezas, Mario Faúndez, Christian Espinosa-Bustos and Cristian O. Salas
Pharmaceutics 2022, 14(6), 1294; https://doi.org/10.3390/pharmaceutics14061294 - 17 Jun 2022
Cited by 4 | Viewed by 2021
Abstract
We report 31 new compounds designed, synthesized and evaluated on Bcr-Abl, BTK and FLT3-ITD as part of our program to develop 2,6,9-trisubstituted purine derivatives as inhibitors of oncogenic kinases. The design was inspired by the chemical structures of well-known kinase inhibitors and our [...] Read more.
We report 31 new compounds designed, synthesized and evaluated on Bcr-Abl, BTK and FLT3-ITD as part of our program to develop 2,6,9-trisubstituted purine derivatives as inhibitors of oncogenic kinases. The design was inspired by the chemical structures of well-known kinase inhibitors and our previously developed purine derivatives. The synthesis of these purines was simple and used a microwave reactor for the final step. Kinase assays showed three inhibitors with high selectivity for each protein that were identified: 4f (IC50 = 70 nM for Bcr-Abl), 5j (IC50 = 0.41 μM for BTK) and 5b (IC50 = 0.38 μM for FLT-ITD). The 3D-QSAR analysis and molecular docking studies suggested that two fragments are potent and selective inhibitors of these three kinases: a substitution at the 6-phenylamino ring and the length and volume of the alkyl group at N-9. The N-7 and the N-methyl-piperazine moiety linked to the aminophenyl ring at C-2 are also requirements for obtaining the activity. Furthermore, most of these purine derivatives were shown to have a significant inhibitory effect in vitro on the proliferation of leukaemia and lymphoma cells (HL60, MV4-11, CEM, K562 and Ramos) at low concentrations. Finally, we show that the selected purines (4i, 5b and 5j) inhibit the downstream signalling of the respective kinases in cell models. Thus, this study provides new evidence regarding how certain chemical modifications of purine ring substituents provide novel inhibitors of target kinases as potential anti-leukaemia drugs. Full article
(This article belongs to the Special Issue Current and Future Cancer Chemoprevention Strategies)
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13 pages, 9660 KiB  
Article
3,4-Dihydroxyphenylethanol (DPE or Hydroxytyrosol) Counteracts ERK1/2 and mTOR Activation, Pro-Inflammatory Cytokine Release, Autophagy and Mitophagy Reduction Mediated by Benzo[a]pyrene in Primary Human Colonic Epithelial Cells
by Roberta Santarelli, Chiara Pompili, Maria Saveria Gilardini Montani, Lorenzo Evangelista, Roberta Gonnella and Mara Cirone
Pharmaceutics 2022, 14(3), 663; https://doi.org/10.3390/pharmaceutics14030663 - 17 Mar 2022
Cited by 6 | Viewed by 2115
Abstract
Understanding the effects induced by carcinogens on primary colonic epithelial cells and how to counteract them might help to prevent colon cancer, which is one of the most frequent and aggressive cancers. In this study, we exposed primary human colonic epithelial cells (HCoEpC) [...] Read more.
Understanding the effects induced by carcinogens on primary colonic epithelial cells and how to counteract them might help to prevent colon cancer, which is one of the most frequent and aggressive cancers. In this study, we exposed primary human colonic epithelial cells (HCoEpC) to Benzo[a]pyrene (B[a]P) and found that it led to an increased production of pro-inflammatory cytokines and activated ERK1/2 and mTOR. These pathways are known to be involved in inflammatory bowel disease (IBD), which represents a colon cancer risk factor. Moreover, B[a]P reduced autophagy and mitophagy, processes whose dysregulation has been clearly demonstrated to predispose to cancer either by in vitro or in vivo studies. Interestingly, all the effects induced by B[a]P could be counteracted by 3,4-Dihydroxyphenylethanol (DPE or Hydroxytyrosol, H), the most powerful anti-inflammatory and antioxidant compound contained in olive oil. This study sheds light on the mechanisms that could be involved in colon carcinogenesis induced by a chemical carcinogen and identifies a safe natural product that may help to prevent them. Full article
(This article belongs to the Special Issue Current and Future Cancer Chemoprevention Strategies)
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30 pages, 7569 KiB  
Article
Programmed Cell Death Alterations Mediated by Synthetic Indole Chalcone Resulted in Cell Cycle Arrest, DNA Damage, Apoptosis and Signaling Pathway Modulations in Breast Cancer Model
by Radka Michalkova, Martin Kello, Zuzana Kudlickova, Maria Gazdova, Ladislav Mirossay, Gabriela Mojzisova and Jan Mojzis
Pharmaceutics 2022, 14(3), 503; https://doi.org/10.3390/pharmaceutics14030503 - 24 Feb 2022
Cited by 11 | Viewed by 2128
Abstract
Although new chemotherapy significantly increased the survival of breast cancer (BC) patients, the use of these drugs is often associated with serious toxicity. The discovery of novel anticancer agents for BC therapy is expected. This study was conducted to explore the antiproliferative effect [...] Read more.
Although new chemotherapy significantly increased the survival of breast cancer (BC) patients, the use of these drugs is often associated with serious toxicity. The discovery of novel anticancer agents for BC therapy is expected. This study was conducted to explore the antiproliferative effect of newly synthesized indole chalcone derivative ZK-CH-11d on human BC cell lines. MTT screening, flow cytometry, Western blot, and fluorescence microscopy were used to evaluate the mode of cell death. ZK-CH-11d significantly suppressed the proliferation of BC cells with minimal effect against non-cancer cells. This effect was associated with cell cycle arrest at the G2/M phase and apoptosis induction. Apoptosis was associated with cytochrome c release, increased activity of caspase 3 and caspase 7, PARP cleavage, reduced mitochondrial membrane potential, and activation of the DNA damage response system. Furthermore, our study demonstrated that ZK-CH-11d increased the AMPK phosphorylation with simultaneous inhibition of the PI3K/Akt/mTOR pathway indicating autophagy initiation. However, chloroquine, an autophagy inhibitor, significantly potentiated the cytotoxic effect of ZK-CH-11d in MDA-MB-231 cells indicating that autophagy is not principally involved in the antiproliferative effect of ZK-CH-11d. Taking together the results from our experiments, we assume that autophagy was activated as a defense mechanism in treated cells trying to escape from chalcone-induced harmful effects. Full article
(This article belongs to the Special Issue Current and Future Cancer Chemoprevention Strategies)
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12 pages, 6107 KiB  
Article
Chemoprevention of Urothelial Cell Carcinoma Tumorigenesis by Dietary Flavokawain A in UPII-Mutant Ha-ras Transgenic Mice
by Zhongbo Liu, Liankun Song, Jun Xie, Anne R. Simoneau, Edward Uchio and Xiaolin Zi
Pharmaceutics 2022, 14(3), 496; https://doi.org/10.3390/pharmaceutics14030496 - 24 Feb 2022
Cited by 8 | Viewed by 1201
Abstract
Non-muscle-invasive bladder cancer (NMIBC) has one of the highest recurrence rates among all solid cancers and the highest lifetime treatment cost per patient. Therefore, the development of chemoprevention strategies for reducing the occurrence and recurrence of NMIBC as well as its burdens on [...] Read more.
Non-muscle-invasive bladder cancer (NMIBC) has one of the highest recurrence rates among all solid cancers and the highest lifetime treatment cost per patient. Therefore, the development of chemoprevention strategies for reducing the occurrence and recurrence of NMIBC as well as its burdens on the healthcare system is valuable. Our aim was to determine whether flavokawain A (FKA), a kava chalcone isolated from the kava plant, can target the in vivo activated Ha-ras pathway for prevention and treatment of NMIBC. UPII-mutant Ha-ras transgenic mice that develop papillary urothelial cell carcinoma were fed orally with vehicle control or FKA-formulated food for 6 months starting at 6 weeks of age. Seventy-nine percent (15/19) of male mice fed with 6 g FKA per kilogram (kg) of food survived beyond the 6 months of treatment, while 31.6% (6/19) of control food-fed male mice survived the 6-month treatment period (p = 0.02). The mean bladder weights in FKA vs. control food-fed mice were 0.216 ± 0.033 vs. 0.342 ± 0.039 g in male mice (p = 0.0413) and 0.043 ± 0.004 vs. 0.073 ± 0.004 g in female mice (p < 0.0001); FKA reduced bladder weight by 37% and 41%, respectively. The tumor burdens, determined by the wet bladder weight, in these mice were inversely related to plasma FKA concentrations. In addition to decreased bladder weight, FKA treatment significantly reduced the incidences of hydronephrosis and hematuria. FKA-treated mice exhibited more well-differentiated tumors in the bladder and ureter. Immunohistochemical analysis of FKA-treated tumors compared to those in the control group revealed fewer Ki-67- and survivin-positive cells and an increased number of p27- and TUNEL-positive cells, indicating that FKA inhibits proliferation and induces apoptosis. Overall, the results suggest that FKA can target the in vivo activated Ha-ras pathway for the prevention and treatment of NMIBC. Full article
(This article belongs to the Special Issue Current and Future Cancer Chemoprevention Strategies)
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22 pages, 4550 KiB  
Article
Identification of a Quinone Derivative as a YAP/TEAD Activity Modulator from a Repurposing Library
by Angela Lauriola, Elisa Uliassi, Matteo Santucci, Maria Laura Bolognesi, Marco Mor, Laura Scalvini, Gian Marco Elisi, Gaia Gozzi, Lorenzo Tagliazucchi, Gaetano Marverti, Stefania Ferrari, Lorena Losi, Domenico D’Arca and Maria Paola Costi
Pharmaceutics 2022, 14(2), 391; https://doi.org/10.3390/pharmaceutics14020391 - 10 Feb 2022
Cited by 1 | Viewed by 2028
Abstract
The transcriptional regulators YAP (Yes-associated protein) and TAZ (transcriptional co-activator with PDZ-binding motif) are the major downstream effectors in the Hippo pathway and are involved in cancer progression through modulation of the activity of TEAD (transcriptional enhanced associate domain) transcription factors. To exploit [...] Read more.
The transcriptional regulators YAP (Yes-associated protein) and TAZ (transcriptional co-activator with PDZ-binding motif) are the major downstream effectors in the Hippo pathway and are involved in cancer progression through modulation of the activity of TEAD (transcriptional enhanced associate domain) transcription factors. To exploit the advantages of drug repurposing in the search of new drugs, we developed a similar approach for the identification of new hits interfering with TEAD target gene expression. In our study, a 27-member in-house library was assembled, characterized, and screened for its cancer cell growth inhibition effect. In a secondary luciferase-based assay, only seven compounds confirmed their specific involvement in TEAD activity. IA5 bearing a p-quinoid structure reduced the cytoplasmic level of phosphorylated YAP and the YAP–TEAD complex transcriptional activity and reduced cancer cell growth. IA5 is a promising hit compound for TEAD activity modulator development. Full article
(This article belongs to the Special Issue Current and Future Cancer Chemoprevention Strategies)
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11 pages, 2695 KiB  
Article
Arctiin Inhibits Cervical Cancer Cell Migration and Invasion through Suppression of S100A4 Expression via PI3K/Akt Pathway
by Chung-Yuan Lee, Min-Chieh Hsin, Pei-Ni Chen, Chiao-Wen Lin, Po-Hui Wang, Shun-Fa Yang and Yi-Hsuan Hsiao
Pharmaceutics 2022, 14(2), 365; https://doi.org/10.3390/pharmaceutics14020365 - 05 Feb 2022
Cited by 8 | Viewed by 1723
Abstract
Arctiin, a lignan glycoside, is isolated from Arctium lappa L. The anticancer effects of arctiin have been demonstrated in several studies. However, no research has been conducted on the anti-migration effect of arctiin in cervical cancer cells. The present study examined the effects [...] Read more.
Arctiin, a lignan glycoside, is isolated from Arctium lappa L. The anticancer effects of arctiin have been demonstrated in several studies. However, no research has been conducted on the anti-migration effect of arctiin in cervical cancer cells. The present study examined the effects of arctiin on cervical cancer cells and investigated the possible molecular mechanism. We demonstrated that arctiin exhibited low cytotoxicity and significantly inhibited cell migration and invasion in human cervical cancer cells. The S100A4 protein expression and mRNA levels were significantly reduced in HeLa and SiHa cells with arctiin treatment. Furthermore, silencing S100A4 by using small interfering RNA reduced cell migration, while overexpression of S100A4 mitigated the migration inhibition imposed by arctiin in cervical cancer cells. Western blotting revealed that arctiin significantly reduced phosphoinositide 3-kinase (PI3K) and phosphorylation of Akt in cervical cancer cells. Moreover, selective Akt induction by an Akt activator, SC-79, reverted cervical cancer cell migration and S100A4 protein expression, which were reduced in response to arctiin. Taken together, these results suggest that arctiin inhibits cervical cancer cell migration and invasion through suppression of S100A4 and the PI3K/Akt pathway. Full article
(This article belongs to the Special Issue Current and Future Cancer Chemoprevention Strategies)
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14 pages, 2534 KiB  
Article
The Natural Chemotherapeutic Capsaicin Activates AMPK through LKB1 Kinase and TRPV1 Receptors in Prostate Cancer Cells
by Belén G. Sánchez, Alicia Bort, José M. Mora-Rodríguez and Inés Díaz-Laviada
Pharmaceutics 2022, 14(2), 329; https://doi.org/10.3390/pharmaceutics14020329 - 29 Jan 2022
Cited by 5 | Viewed by 2847
Abstract
The natural bioactive compound capsaicin has been reported to have anticancer activity, although the underlying mechanism of action has not been completely clarified. Herein, we investigated the mechanism whereby capsaicin exerts antitumor effects on prostate cancer cells. We found that capsaicin activated AMP-activated [...] Read more.
The natural bioactive compound capsaicin has been reported to have anticancer activity, although the underlying mechanism of action has not been completely clarified. Herein, we investigated the mechanism whereby capsaicin exerts antitumor effects on prostate cancer cells. We found that capsaicin activated AMP-activated kinase (AMPK) and promoted cell death in the LKB1-expressing prostate cancer cell lines LNCaP and PC3, but not in the liver kinase B1 (LKB1)-null cell line DU-145. Capsaicin treatment stimulated LKB1 phosphorylation and activated AMPK in LKB1-expressing cells. In addition, LKB1 silencing in LNCaP and PC3 cells abrogated capsaicin-induced AMPK activation, while the overexpression of LKB1 by lentiviral infection in DU-145 cells induced capsaicin-triggered AMPK phosphorylation. Moreover, the calcium/calmodulin-dependent kinase kinase 2 (CaMKK2) inhibitor STO-609 did not modify the activation of AMPK induced by capsaicin, suggesting a CaMKK2-independent mechanism. Capsaicin-induced LKB1 phosphorylation was dependent on the transient receptor potential cation channel subfamily V member 1 (TRPV1), since TRPV1 knocked down by shRNA abolished LKB1 and AMPK phosphorylation in LKB1-expressing cells. Altogether, our results showed that capsaicin affected AMPK activity in an LKB1- and TRPV1-dependent fashion, linking TRPV1 with cell fate. These data also suggest that capsaicin may be a rational chemotherapeutic option for prostate tumors. Full article
(This article belongs to the Special Issue Current and Future Cancer Chemoprevention Strategies)
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15 pages, 27495 KiB  
Article
Sesame Extract Promotes Chemopreventive Effect of Hesperidin on Early Phase of Diethylnitrosamine-Initiated Hepatocarcinogenesis in Rats
by Napaporn Khuanphram, Sirinya Taya, Prachya Kongtawelert and Rawiwan Wongpoomchai
Pharmaceutics 2021, 13(10), 1687; https://doi.org/10.3390/pharmaceutics13101687 - 14 Oct 2021
Cited by 7 | Viewed by 1798
Abstract
The combination of natural products is an alternative approach to achieving chemopreventive potential. Accordingly, citrus hesperidin exhibits numerous biological activities, including anticarcinogenic activities, while the sesamin in sesame exhibits potent anticancer activities and lipid-lowering effects. We investigated the cancer chemopreventive effects of mixed [...] Read more.
The combination of natural products is an alternative approach to achieving chemopreventive potential. Accordingly, citrus hesperidin exhibits numerous biological activities, including anticarcinogenic activities, while the sesamin in sesame exhibits potent anticancer activities and lipid-lowering effects. We investigated the cancer chemopreventive effects of mixed sesame and orange seed extract (MSO) containing hesperidin and sesamin in diethylnitrosamine (DEN)-induced hepatocarcinogenesis. Rats were injected with DEN once a week for 3 weeks to induce hepatocarcinogenesis. Rats were fed with MSO and various compositions that included sesame extract (SE) and hesperidin. The 10-week administration of MSO more effectively inhibited the number and size of hepatic GST-P-positive foci than hesperidin in DEN-initiated rats. MSO and hesperidin decreased the number of PCNA-positive hepatocytes but increased the apoptotic cells in DEN-induced rats. Furthermore, MSO and its constituents suppressed hepatic triglyceride content concurrently along with the expression of fatty acid synthase. Although the 5-week administration of MSO or hesperidin did not alter hepatic, preneoplastic lesion formation in DEN-initiated rats, it alleviated DEN-induced hepatotoxicity. MSO and its applied compositions did not impact upon the cytochrome P450 system. In conclusion, sesame extract promoted the chemopreventive effect of hesperidin on DEN-induced early stage of hepatocarcinogenesis in rats. The inhibitory mechanisms are likely involved with the induction of cell apoptosis, suppression of cell proliferation and modulation of hepatic lipogenesis. This study may provide revelations in the development of alternative treatments against hepatocellular carcinoma. Full article
(This article belongs to the Special Issue Current and Future Cancer Chemoprevention Strategies)
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Review

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19 pages, 2421 KiB  
Review
Role of Nrf2, STAT3, and Src as Molecular Targets for Cancer Chemoprevention
by Haseeb Ahsan, Salman Ul Islam, Muhammad Bilal Ahmed and Young Sup Lee
Pharmaceutics 2022, 14(9), 1775; https://doi.org/10.3390/pharmaceutics14091775 - 25 Aug 2022
Cited by 6 | Viewed by 2100
Abstract
Cancer is a complex and multistage disease that affects various intracellular pathways, leading to rapid cell proliferation, angiogenesis, cell motility, and migration, supported by antiapoptotic mechanisms. Chemoprevention is a new strategy to counteract cancer; to either prevent its incidence or suppress its progression. [...] Read more.
Cancer is a complex and multistage disease that affects various intracellular pathways, leading to rapid cell proliferation, angiogenesis, cell motility, and migration, supported by antiapoptotic mechanisms. Chemoprevention is a new strategy to counteract cancer; to either prevent its incidence or suppress its progression. In this strategy, chemopreventive agents target molecules involved in multiple pathways of cancer initiation and progression. Nrf2, STAT3, and Src are promising molecular candidates that could be targeted for chemoprevention. Nrf2 is involved in the expression of antioxidant and phase II metabolizing enzymes, which have direct antiproliferative action as well as indirect activities of reducing oxidative stress and eliminating carcinogens. Similarly, its cross-talk with NF-κB has great anti-inflammatory potential, which can be utilized in inflammation-induced/associated cancers. STAT3, on the other hand, is involved in multiple pathways of cancer initiation and progression. Activation, phosphorylation, dimerization, and nuclear translocation are associated with tumor cell proliferation and angiogenesis. Src, being the first oncogene to be discovered, is important due to its convergence with many upstream stimuli, its cross-talk with other potential molecular targets, such as STAT3, and its ability to modify the cell cytoskeleton, making it important in cancer invasion and metastasis. Therefore, the development of natural/synthetic molecules and/or design of a regimen that can reduce oxidative stress and inflammation in the tumor microenvironment and stop multiple cellular targets in cancer to stop its initiation or retard its progression can form newer chemopreventive agents. Full article
(This article belongs to the Special Issue Current and Future Cancer Chemoprevention Strategies)
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31 pages, 3465 KiB  
Review
Scope and Limitations of Current Antibiotic Therapies against Helicobacter pylori: Reviewing Amoxicillin Gastroretentive Formulations
by Roberto Grosso and M.-Violante de-Paz
Pharmaceutics 2022, 14(7), 1340; https://doi.org/10.3390/pharmaceutics14071340 - 24 Jun 2022
Cited by 3 | Viewed by 2389
Abstract
Even though general improvement of quality of life has happened around the globe, statistics show that gastric cancer is still a very serious medical concern in some regions of the world. A big portion of malignant neoplasms that develop inside the stomach are [...] Read more.
Even though general improvement of quality of life has happened around the globe, statistics show that gastric cancer is still a very serious medical concern in some regions of the world. A big portion of malignant neoplasms that develop inside the stomach are linked to an infection of Helicobacter pylori; in fact, this pathogen has already been categorized as a group 1 carcinogen by the World Health Organization (WHO). Still, the efficacy of current anti-H. pylori therapeutic approaches is insufficient and follows a worrying decreasing trend, mainly due to an exponential increase in resistance to key antibiotics. This work analyzes the clinical and biological characteristics of this pathogen, especially its link to gastric cancer, and provides a comprehensive review of current formulation trends for H. pylori eradication. Research effort has focused both on the discovery of new combinations of chemicals that function as optimized antibiotic regimens, and on the preparation of gastroretentive drug delivery systems (GRDDSs) to improve overall pharmacokinetics. Regarding the last topic, this review aims to summarize the latest trend in amoxicillin-loaded GRDDS, since this is the antibiotic that has shown the least bacterial resistance worldwide. It is expected that the current work could provide some insight into the importance of innovative options to combat this microorganism. Therefore, this review can inspire new research strategies in the development of efficient formulations for the treatment of this infection and the consequent prevention of gastric cancer. Full article
(This article belongs to the Special Issue Current and Future Cancer Chemoprevention Strategies)
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46 pages, 3417 KiB  
Review
Angioprevention of Urologic Cancers by Plant-Derived Foods
by Melissa García-Caballero, José Antonio Torres-Vargas, Ana Dácil Marrero, Beatriz Martínez-Poveda, Miguel Ángel Medina and Ana R. Quesada
Pharmaceutics 2022, 14(2), 256; https://doi.org/10.3390/pharmaceutics14020256 - 21 Jan 2022
Cited by 11 | Viewed by 4114
Abstract
The number of cancer cases worldwide keeps growing unstoppably, despite the undeniable advances achieved by basic research and clinical practice. Urologic tumors, including some as prevalent as prostate, bladder or kidney tumors, are no exceptions to this rule. Moreover, the fact that many [...] Read more.
The number of cancer cases worldwide keeps growing unstoppably, despite the undeniable advances achieved by basic research and clinical practice. Urologic tumors, including some as prevalent as prostate, bladder or kidney tumors, are no exceptions to this rule. Moreover, the fact that many of these tumors are detected in early stages lengthens the duration of their treatment, with a significant increase in health care costs. In this scenario, prevention offers the most cost-effective long-term strategy for the global control of these diseases. Although specialized diets are not the only way to decrease the chances to develop cancer, epidemiological evidence support the role of certain plant-derived foods in the prevention of urologic cancer. In many cases, these plants are rich in antiangiogenic phytochemicals, which could be responsible for their protective or angiopreventive properties. Angiogenesis inhibition may contribute to slow down the progression of the tumor at very different stages and, for this reason, angiopreventive strategies could be implemented at different levels of chemoprevention, depending on the targeted population. In this review, epidemiological evidence supporting the role of certain plant-derived foods in urologic cancer prevention are presented, with particular emphasis on their content in bioactive phytochemicals that could be used in the angioprevention of cancer. Full article
(This article belongs to the Special Issue Current and Future Cancer Chemoprevention Strategies)
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35 pages, 19836 KiB  
Review
Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention
by Dusan Ruzic, Nemanja Djoković, Tatjana Srdić-Rajić, Cesar Echeverria, Katarina Nikolic and Juan F. Santibanez
Pharmaceutics 2022, 14(1), 209; https://doi.org/10.3390/pharmaceutics14010209 - 16 Jan 2022
Cited by 28 | Viewed by 3414
Abstract
The dysregulation of gene expression is a critical event involved in all steps of tumorigenesis. Aberrant histone and non-histone acetylation modifications of gene expression due to the abnormal activation of histone deacetylases (HDAC) have been reported in hematologic and solid types of cancer. [...] Read more.
The dysregulation of gene expression is a critical event involved in all steps of tumorigenesis. Aberrant histone and non-histone acetylation modifications of gene expression due to the abnormal activation of histone deacetylases (HDAC) have been reported in hematologic and solid types of cancer. In this sense, the cancer-associated epigenetic alterations are promising targets for anticancer therapy and chemoprevention. HDAC inhibitors (HDACi) induce histone hyperacetylation within target proteins, altering cell cycle and proliferation, cell differentiation, and the regulation of cell death programs. Over the last three decades, an increasing number of synthetic and naturally derived compounds, such as dietary-derived products, have been demonstrated to act as HDACi and have provided biological and molecular insights with regard to the role of HDAC in cancer. The first part of this review is focused on the biological roles of the Zinc-dependent HDAC family in malignant diseases. Accordingly, the small-molecules and natural products such as HDACi are described in terms of cancer therapy and chemoprevention. Furthermore, structural considerations are included to improve the HDACi selectivity and combinatory potential with other specific targeting agents in bifunctional inhibitors and proteolysis targeting chimeras. Additionally, clinical trials that combine HDACi with current therapies are discussed, which may open new avenues in terms of the feasibility of HDACi’s future clinical applications in precision cancer therapies. Full article
(This article belongs to the Special Issue Current and Future Cancer Chemoprevention Strategies)
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12 pages, 3141 KiB  
Review
Combination Therapy of Navitoclax with Chemotherapeutic Agents in Solid Tumors and Blood Cancer: A Review of Current Evidence
by Nur Syahidah Nor Hisam, Azizah Ugusman, Nor Fadilah Rajab, Mohd Faizal Ahmad, Michael Fenech, Sze Ling Liew and Nur Najmi Mohamad Anuar
Pharmaceutics 2021, 13(9), 1353; https://doi.org/10.3390/pharmaceutics13091353 - 28 Aug 2021
Cited by 18 | Viewed by 4063
Abstract
Combination therapy emerges as a fundamental scheme in cancer. Many targeted therapeutic agents are developed to be used with chemotherapy or radiation therapy to enhance drug efficacy and reduce toxicity effects. ABT-263, known as navitoclax, mimics the BH3-only proteins of the BCL-2 family [...] Read more.
Combination therapy emerges as a fundamental scheme in cancer. Many targeted therapeutic agents are developed to be used with chemotherapy or radiation therapy to enhance drug efficacy and reduce toxicity effects. ABT-263, known as navitoclax, mimics the BH3-only proteins of the BCL-2 family and has a high affinity towards pro-survival BCL-2 family proteins (i.e., BCL-XL, BCL-2, BCL-W) to induce cell apoptosis effectively. A single navitoclax action potently ameliorates several tumor progressions, including blood and bone marrow cancer, as well as small cell lung carcinoma. Not only that, but navitoclax alone also therapeutically affects fibrotic disease. Nevertheless, outcomes from the clinical trial of a single navitoclax agent in patients with advanced and relapsed small cell lung cancer demonstrated a limited anti-cancer activity. This brings accumulating evidence of navitoclax to be used concomitantly with other chemotherapeutic agents in several solid and non-solid tumors that are therapeutically benefiting from navitoclax treatment in preclinical studies. Initially, we justify the anti-cancer role of navitoclax in combination therapy. Then, we evaluate the current evidence of navitoclax in combination with the chemotherapeutic agents comprehensively to indicate the primary regulator of this combination strategy in order to produce a therapeutic effect. Full article
(This article belongs to the Special Issue Current and Future Cancer Chemoprevention Strategies)
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34 pages, 1025 KiB  
Review
Inhibitors of the PI3K/Akt/mTOR Pathway in Prostate Cancer Chemoprevention and Intervention
by Nazanin Momeni Roudsari, Naser-Aldin Lashgari, Saeideh Momtaz, Shaghayegh Abaft, Fatemeh Jamali, Pardis Safaiepour, Kiyana Narimisa, Gloria Jackson, Anusha Bishayee, Nima Rezaei, Amir Hossein Abdolghaffari and Anupam Bishayee
Pharmaceutics 2021, 13(8), 1195; https://doi.org/10.3390/pharmaceutics13081195 - 03 Aug 2021
Cited by 31 | Viewed by 4984
Abstract
The phosphatidylinositol 3-kinase (PI3K)/serine-threonine kinase (Akt)/mammalian target of the rapamycin (mTOR)-signaling pathway has been suggested to have connections with the malignant transformation, growth, proliferation, and metastasis of various cancers and solid tumors. Relevant connections between the PI3K/Akt/mTOR pathway, cell survival, and prostate cancer [...] Read more.
The phosphatidylinositol 3-kinase (PI3K)/serine-threonine kinase (Akt)/mammalian target of the rapamycin (mTOR)-signaling pathway has been suggested to have connections with the malignant transformation, growth, proliferation, and metastasis of various cancers and solid tumors. Relevant connections between the PI3K/Akt/mTOR pathway, cell survival, and prostate cancer (PC) provide a great therapeutic target for PC prevention or treatment. Recent studies have focused on small-molecule mTOR inhibitors or their usage in coordination with other therapeutics for PC treatment that are currently undergoing clinical testing. In this study, the function of the PI3K/Akt/mTOR pathway, the consequence of its dysregulation, and the development of mTOR inhibitors, either as an individual substance or in combination with other agents, and their clinical implications are discussed. The rationale for targeting the PI3K/Akt/mTOR pathway, and specifically the application and potential utility of natural agents involved in PC treatment is described. In addition to the small-molecule mTOR inhibitors, there are evidence that several natural agents are able to target the PI3K/Akt/mTOR pathway in prostatic neoplasms. These natural mTOR inhibitors can interfere with the PI3K/Akt/mTOR pathway through multiple mechanisms; however, inhibition of Akt and suppression of mTOR 1 activity are two major therapeutic approaches. Combination therapy improves the efficacy of these inhibitors to either suppress the PC progression or circumvent the resistance by cancer cells. Full article
(This article belongs to the Special Issue Current and Future Cancer Chemoprevention Strategies)
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