Natural Products in the Treatment of Cancer

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 12983

Special Issue Editor


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Guest Editor
Department of Pharmaceutical Sciences, School of Pharmacy, Cedarville University, Cedarville, OH, USA
Interests: natural product; brain tumor; anticancer

Special Issue Information

Dear Colleagues,

Cancer has always been a hot topic in human disease research, and natural products have made significant contributions to cancer treatment in the past dozen years and are still an important source of anticancer drug discovery today. The rapid development of synthetic drugs has also been promoted by the chemical structural leading, modification, and transformation of natural products. Natural products are widely found in foods such as fruits, vegetables, fungi, and spices, which are very beneficial to the prevention of human cancer. With the gradual deepening of research on natural products, the research turns to focus on new drugs which develop and utilization of natural products and some new anti-cancer ingredients. And it opens up new ideas and methods for people to find new anti-cancer methods way.

This Special Issue aims to discuss the novel Insights into the natural products in the treatment of cancer, and it will include the molecular mechanism of natural products and their derivatives for the treatment of cancer.

Dr. Samson Amos
Guest Editor

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Keywords

  • cancer
  • natural
  • products
  • herbal products
  • cell signaling
  • drug formulation
  • natural product chemistry
  • cancer biology

Published Papers (7 papers)

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Research

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15 pages, 6002 KiB  
Article
Disruption of Glioblastoma Multiforme Cell Circuits with Cinnamaldehyde Highlights Potential Targets with Implications for Novel Therapeutic Strategies
by Shraddha Srivastava, Ketki Patil, Elizabeth W. Thompson, Shadi A. Nakhai, Yoo Na Kim, Casey Haynes, Crystal Bryant and S. Balakrishna Pai
Cells 2023, 12(9), 1277; https://doi.org/10.3390/cells12091277 - 28 Apr 2023
Viewed by 1518
Abstract
Glioblastoma multiforme (GBM) is a major aggressive primary brain tumor with dismal survival outcome and few therapeutic options. Although Temozolomide (TMZ) is a part of the standard therapy, over time, it can cause DNA damage leading to deleterious effects, necessitating the discovery of [...] Read more.
Glioblastoma multiforme (GBM) is a major aggressive primary brain tumor with dismal survival outcome and few therapeutic options. Although Temozolomide (TMZ) is a part of the standard therapy, over time, it can cause DNA damage leading to deleterious effects, necessitating the discovery of drugs with minimal side effects. To this end, we investigated the effect of cinnamaldehyde (CA), a highly purified, single ingredient from cinnamon, on the GBM cell lines U87 and U251 and the neuroglioma cell line H4. On observing similar impact on the viability in all the three cell lines, detailed studies were conducted with CA and its isomer/analog, trans-CA (TCA), and methoxy-CA (MCA) on U87 cells. The compounds exhibited equal potency when assessed at the cellular level in inhibiting U87 cells as well as at the molecular level, resulting in an increase in reactive oxygen species (ROS) and an increase in the apoptotic and multicaspase cell populations. To further characterize the key entities, protein profiling was performed with CA. The studies revealed differential regulation of entities that could be key to glioblastoma cell circuits such as downregulation of pyruvate kinase-PKM2, the key enzyme of the glycolytic pathway that is central to the Warburg effect. This allows for monitoring the levels of PKM2 after therapy using recently developed noninvasive technology employing PET [18F] DASA-23. Additionally, the observation of downregulation of phosphomevalonate kinase is significant as the brain tumor initiating cells (BTIC) are maintained by the metabolism occurring via the mevalonate pathway. Results from the current study, if translated in vivo, could provide additional efficacious treatment options for glioblastoma with minimal side effects. Full article
(This article belongs to the Special Issue Natural Products in the Treatment of Cancer)
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20 pages, 6241 KiB  
Article
Impact of Synthesized Indoloquinoline Analog to Isolates from Cryptolepis sanguinolenta on Tumor Growth Inhibition and Hepatotoxicity in Ehrlich Solid Tumor-Bearing Female Mice
by Amany E. Nofal, Elshaymaa I. Elmongy, Engy Abo Hassan, Ehab Tousson, Abdullah A. S. Ahmed, Ibrahim El Tantawy El Sayed, Reem Binsuwaidan and Manar Sakr
Cells 2023, 12(7), 1024; https://doi.org/10.3390/cells12071024 - 27 Mar 2023
Cited by 4 | Viewed by 1479
Abstract
The study evaluated the antitumor efficacy of APAN, “synthesized indoloquinoline analog derived from the parent neocryptolepine isolated from the roots of Cryptolepis sanguinolenta”, versus the chemotherapeutic drug etoposide (ETO) in Ehrlich solid tumor (EST)-bearing female mice as well as its protective effect [...] Read more.
The study evaluated the antitumor efficacy of APAN, “synthesized indoloquinoline analog derived from the parent neocryptolepine isolated from the roots of Cryptolepis sanguinolenta”, versus the chemotherapeutic drug etoposide (ETO) in Ehrlich solid tumor (EST)-bearing female mice as well as its protective effect against etoposide-triggered hepatic disorders. APAN showed an ameliorative activity against Ehrlich solid tumor and hepatic toxicity, and the greatest improvement was found in the combined treatment of APAN with ETO. The results indicated that EST altered the levels of tumor markers (AFP, CEA, and anti-dsDNA) and liver biomarker function (ALT, AST, ALP, ALB, and T. protein). Furthermore, EST elevated CD68 and anti-survivin proteins immuno-expressions in the solid tumor and liver tissue. Molecular docking studies were demonstrated to investigate their affinity for both TNF-α and topoisomerase II as target proteins, as etoposide is based on the inhibition of topoisomerase II, and TNF-α is quite highly expressed in the solid tumor and liver tissues of EST-bearing animals, which prompted the authors’ interest to explore APAN affinity to its binding site. Treatment of mice bearing EST with APAN and ETO nearly regularized serum levels of the altered parameters and ameliorated the impact of EST on the tissue structure of the liver better than that by treatment with each of them separately. Full article
(This article belongs to the Special Issue Natural Products in the Treatment of Cancer)
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30 pages, 25923 KiB  
Article
Understanding the Combined Effects of High Glucose Induced Hyper-Osmotic Stress and Oxygen Tension in the Progression of Tumourigenesis: From Mechanism to Anti-Cancer Therapeutics
by Gayathri K. G., Puja Laxmanrao Shinde, Sebastian John, Sivakumar K. C. and Rashmi Mishra
Cells 2023, 12(6), 825; https://doi.org/10.3390/cells12060825 - 07 Mar 2023
Cited by 2 | Viewed by 2298
Abstract
High glucose (HG), a hallmark of the tumour microenvironment, is also a biomechanical stressor, as it exerts hyper-osmotic stress (HG-HO), but not much is known regarding how tumour cells mechanoadapt to HG-HO. Therefore, this study aimed to delineate the novel molecular mechanisms by [...] Read more.
High glucose (HG), a hallmark of the tumour microenvironment, is also a biomechanical stressor, as it exerts hyper-osmotic stress (HG-HO), but not much is known regarding how tumour cells mechanoadapt to HG-HO. Therefore, this study aimed to delineate the novel molecular mechanisms by which tumour cells mechanoadapt to HG/HG-HO and whether phytochemical-based interference in these mechanisms can generate tumour-cell-selective vulnerability to cell death. Mannitol and L-glucose were used as hyper-osmotic equivalents of high glucose. The results revealed that the tumour cells can efficiently mechanoadapt to HG-HO only in the normoxic microenvironment. Under normoxic HG/HG-HO stress, tumour cells polySUMOylate a higher pool of mitotic driver pH3(Ser10), which translocates to the nucleus and promotes faster cell divisions. On the contrary, acute hypoxia dampens HG/HG-HO-associated excessive proliferation by upregulating sentrin protease SENP7. SENP7 promotes abnormal SUMOylation of pH3(Ser10), thereby restricting its nuclear entry and promoting the M-phase arrest and cell loss. However, the hypoxia-arrested cells that managed to survive showed relapse upon reversal to normoxia as well as upregulation of pro-survival-associated SENP1, and players in tumour growth signalling, autophagy, glycolytic pathways etc. Depletion of SENP1 in both normoxia and hypoxia caused significant loss of tumour cells vs undepleted controls. SENP1 was ascertained to restrict the abnormal SUMOylation of pH3(Ser10) in both normoxia and hypoxia, although not so efficiently in hypoxia, due to the opposing activity of SENP7. Co-treatment with Momordin Ic (MC), a natural SENP1 inhibitor, and Gallic Acid (GA), an inhibitor of identified major pro-tumourigenic signalling (both enriched in Momordica charantia), eliminated surviving tumour cells in normal glucose, HG and HG-HO normoxic and hypoxic microenvironments, suggesting that appropriate and enhanced polySUMOylation of pH3(Ser10) in response to HG/HG-HO stress was attenuated by this treatment along with further dampening of other key tumourigenic signalling, due to which tumour cells could no longer proliferate and grow. Full article
(This article belongs to the Special Issue Natural Products in the Treatment of Cancer)
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22 pages, 4577 KiB  
Article
Molecular Mechanisms of Nemorosone-Induced Ferroptosis in Cancer Cells
by Roberto Fernández-Acosta, Behrouz Hassannia, Jurgen Caroen, Bartosz Wiernicki, Daniel Alvarez-Alminaque, Bruno Verstraeten, Johan Van der Eycken, Peter Vandenabeele, Tom Vanden Berghe and Gilberto L. Pardo-Andreu
Cells 2023, 12(5), 735; https://doi.org/10.3390/cells12050735 - 24 Feb 2023
Cited by 4 | Viewed by 1957
Abstract
Ferroptosis is an iron-dependent cell death-driven by excessive peroxidation of polyunsaturated fatty acids (PUFAs) of membranes. A growing body of evidence suggests the induction of ferroptosis as a cutting-edge strategy in cancer treatment research. Despite the essential role of mitochondria in cellular metabolism, [...] Read more.
Ferroptosis is an iron-dependent cell death-driven by excessive peroxidation of polyunsaturated fatty acids (PUFAs) of membranes. A growing body of evidence suggests the induction of ferroptosis as a cutting-edge strategy in cancer treatment research. Despite the essential role of mitochondria in cellular metabolism, bioenergetics, and cell death, their function in ferroptosis is still poorly understood. Recently, mitochondria were elucidated as an important component in cysteine-deprivation-induced (CDI) ferroptosis, which provides novel targets in the search for new ferroptosis-inducing compounds (FINs). Here, we identified the natural mitochondrial uncoupler nemorosone as a ferroptosis inducer in cancer cells. Interestingly, nemorosone triggers ferroptosis by a double-edged mechanism. In addition to decreasing the glutathione (GSH) levels by blocking the System xc cystine/glutamate antiporter (SLC7A11), nemorosone increases the intracellular labile Fe2+ pool via heme oxygenase-1 (HMOX1) induction. Interestingly, a structural variant of nemorosone (O-methylated nemorosone), having lost the capacity to uncouple mitochondrial respiration, does not trigger cell death anymore, suggesting that the mitochondrial bioenergetic disruption via mitochondrial uncoupling is necessary for nemorosone-induced ferroptosis. Our results open novel opportunities for cancer cell killing by mitochondrial uncoupling-induced ferroptosis. Full article
(This article belongs to the Special Issue Natural Products in the Treatment of Cancer)
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14 pages, 1951 KiB  
Article
Evaluation of Possible Neobavaisoflavone Chemosensitizing Properties towards Doxorubicin and Etoposide in SW1783 Anaplastic Astrocytoma Cells
by Mateusz Maszczyk, Klaudia Banach, Jakub Rok, Zuzanna Rzepka, Artur Beberok and Dorota Wrześniok
Cells 2023, 12(4), 593; https://doi.org/10.3390/cells12040593 - 12 Feb 2023
Viewed by 1308
Abstract
Flavonoids exert many beneficial properties, such as anticancer activity. They were found to have chemopreventive effects hindering carcinogenesis, and also being able to affect processes important for cancer cell pathophysiology inhibiting its growth or promoting cell death. There are also reports on the [...] Read more.
Flavonoids exert many beneficial properties, such as anticancer activity. They were found to have chemopreventive effects hindering carcinogenesis, and also being able to affect processes important for cancer cell pathophysiology inhibiting its growth or promoting cell death. There are also reports on the chemosensitizing properties of flavonoids, which indicate that they could be used as a support of anticancer therapy. It gives promise for a novel therapeutic approach in tumors characterized by ineffective treatment, such as high-grade gliomas. The research was conducted on the in vitro culture of human SW1783 anaplastic astrocytoma cells incubated with neobavaisoflavone (NEO), doxorubicin, etoposide, and their combinations with NEO. The analyses involved the WST-1 cell viability assay and image cytometry techniques including cell count assay, Annexin V assay, the evaluation of mitochondrial membrane potential, and the cell-cycle phase distribution. We found that NEO affects the activity of doxorubicin and etoposide by reducing the viability of SW1783 cells. The combination of NEO and etoposide caused an increase in the apoptotic and low mitochondrial membrane potential subpopulations of SW1783 cells. Changes in the cell cycle were observed in all combined treatments. These findings indicate a potential chemosensitizing effect exerted by NEO. Full article
(This article belongs to the Special Issue Natural Products in the Treatment of Cancer)
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17 pages, 7729 KiB  
Article
Dimethylmyricacene: An In Vitro and In Silico Study of a Semisynthetic Non-Camptothecin Derivative Compound, Targeting Human DNA Topoisomerase 1B
by Alessio Ottaviani, Federico Iacovelli, Joshua Welsch, Blasco Morozzo della Rocca, Alessandro Desideri, Mattia Falconi, Laurent Calcul, Bill J. Baker and Paola Fiorani
Cells 2022, 11(21), 3486; https://doi.org/10.3390/cells11213486 - 03 Nov 2022
Cited by 1 | Viewed by 1412
Abstract
Human topoisomerase 1B regulates the topological state of supercoiled DNA enabling all fundamental cell processes. This enzyme, which is the unique molecular target of the natural anticancer compound camptothecin, acts by nicking one DNA strand and forming a transient protein–DNA covalent complex. The [...] Read more.
Human topoisomerase 1B regulates the topological state of supercoiled DNA enabling all fundamental cell processes. This enzyme, which is the unique molecular target of the natural anticancer compound camptothecin, acts by nicking one DNA strand and forming a transient protein–DNA covalent complex. The interaction of human topoisomerase 1B and dimethylmyricacene, a compound prepared semisynthetically from myricanol extracted from Myrica cerifera root bark, was investigated using enzymatic activity assays and molecular docking procedures. Dimethylmyricacene was shown to inhibit both the cleavage and the religation steps of the enzymatic reaction, and cell viability of A-253, FaDu, MCF-7, HeLa and HCT-116 tumor cell lines. Full article
(This article belongs to the Special Issue Natural Products in the Treatment of Cancer)
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Review

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30 pages, 2073 KiB  
Review
Capsaicinoids and Their Effects on Cancer: The “Double-Edged Sword” Postulate from the Molecular Scale
by Francisco Luján-Méndez, Octavio Roldán-Padrón, J. Eduardo Castro-Ruíz, Josué López-Martínez and Teresa García-Gasca
Cells 2023, 12(21), 2573; https://doi.org/10.3390/cells12212573 - 04 Nov 2023
Viewed by 2084
Abstract
Capsaicinoids are a unique chemical species resulting from a particular biosynthesis pathway of hot chilies (Capsicum spp.) that gives rise to 22 analogous compounds, all of which are TRPV1 agonists and, therefore, responsible for the pungency of Capsicum fruits. In addition to [...] Read more.
Capsaicinoids are a unique chemical species resulting from a particular biosynthesis pathway of hot chilies (Capsicum spp.) that gives rise to 22 analogous compounds, all of which are TRPV1 agonists and, therefore, responsible for the pungency of Capsicum fruits. In addition to their human consumption, numerous ethnopharmacological uses of chili have emerged throughout history. Today, more than 25 years of basic research accredit a multifaceted bioactivity mainly to capsaicin, highlighting its antitumor properties mediated by cytotoxicity and immunological adjuvancy against at least 74 varieties of cancer, while non-cancer cells tend to have greater tolerance. However, despite the progress regarding the understanding of its mechanisms of action, the benefit and safety of capsaicinoids’ pharmacological use remain subjects of discussion, since capsaicin also promotes epithelial–mesenchymal transition, in an ambivalence that has been referred to as “the double-edge sword”. Here, we update the comparative discussion of relevant reports about capsaicinoids’ bioactivity in a plethora of experimental models of cancer in terms of selectivity, efficacy, and safety. Through an integration of the underlying mechanisms, as well as inherent aspects of cancer biology, we propose mechanistic models regarding the dichotomy of their effects. Finally, we discuss a selection of in vivo evidence concerning capsaicinoids’ immunomodulatory properties against cancer. Full article
(This article belongs to the Special Issue Natural Products in the Treatment of Cancer)
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