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Bioactive Compounds and Therapeutic Targets in Prostate Cancer
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Bioactive Compounds and Therapeutic Targets in Prostate Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 12707

Special Issue Editor

Dr. Gnanasekar Munirathinam

E-Mail Website
Guest Editor
Department of Biomedical Sciences, College of Medicine, University of Illinois, Rockford, IL 61107, USA
Interests: prostate cancer; phytochemicals; dietary alkaloids; prebiotics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Globally, prostate cancer is one of the leading causes of death in men. Routine intake of bioactive compounds from various sources such as plants, diet, and marine organisms could be potentially beneficial in reducing the incidence and death rates, as prostate cancer is characterized by a long latency period from initiation of prostatic intraepithelial neoplasia to development of adenocarcinoma. Although androgen deprivation therapy is the mainstay treatment, there is increased risk of patients developing lethal castration-resistant prostate cancer and treatment-induced neuroendocrine prostate cancer, in addition to experiencing severe side effects. There is increasing evidence that bioactive compounds could serve as alternative treatment or could be used as adjunct therapy with conventional treatments to improve the quality of life and longevity of patients.

This Special Issue invites original research and review articles focused on bioactive compounds that have targets including androgen receptor (AR), AR variants (e.g., AR-V7), PI3K/Akt, mTOR, NF-kB, TGFbeta, EMT, transcription factors (e.g., c-Myc, N-Myc, STAT3, STAT5), mTOR, Wnt-beta catenin, Notch1, HDAC, DNMT3 etc. in prostate cancer cells based on in vitro and in vivo studies.

Dr. Gnanasekar Munirathinam
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • prostate cancer
  • androgen receptor
  • AR-V7
  • castration-resistant prostate cancer
  • dietary alkaloids
  • dietary antioxidants
  • phenolic compounds
  • terpenoids
  • phytochemicals
  • xanthones
  • probiotics
  • preclinical
  • marine bioactive agents
  • molecular target
  • signaling pathways

Related Special Issue

Published Papers (7 papers)

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Research

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19 pages, 9647 KiB  
Article
Alpha-Lipoic Acid Reduces Cell Growth, Inhibits Autophagy, and Counteracts Prostate Cancer Cell Migration and Invasion: Evidence from In Vitro Studies
by Sabrina Bossio, Anna Perri, Raffaella Gallo, Anna De Bartolo, Vittoria Rago, Daniele La Russa, Michele Di Dio, Sandro La Vignera, Aldo E. Calogero, Giovanni Vitale and Antonio Aversa
Int. J. Mol. Sci. 2023, 24(23), 17111; https://doi.org/10.3390/ijms242317111 - 04 Dec 2023
Viewed by 1251
Abstract
Alpha-lipoic acid (ALA) is a natural antioxidant dithiol compound, exerting antiproliferative and antimetastatic effects in various cancer cell lines. In our study, we demonstrated that ALA reduces the cell growth of prostate cancer cells LNCaP and DU-145. Western blot results revealed that in [...] Read more.
Alpha-lipoic acid (ALA) is a natural antioxidant dithiol compound, exerting antiproliferative and antimetastatic effects in various cancer cell lines. In our study, we demonstrated that ALA reduces the cell growth of prostate cancer cells LNCaP and DU-145. Western blot results revealed that in both cancer cells, ALA, by upregulating pmTOR expression, reduced the protein content of two autophagy initiation markers, Beclin-1 and MAPLC3. Concomitantly, MTT assays showed that chloroquine (CQ) exposure, a well-known autophagy inhibitor, reduced cells’ viability. This was more evident for treatment using the combination ALA + CQ, suggesting that ALA can reduce cells’ viability by inhibiting autophagy. In addition, in DU-145 cells we observed that ALA affected the oxidative/redox balance system by deregulating the KEAP1/Nrf2/p62 signaling pathway. ALA decreased ROS production, SOD1 and GSTP1 protein expression, and significantly reduced the cytosolic and nuclear content of the transcription factor Nrf2, concomitantly downregulating p62, suggesting that ALA disrupted p62-Nrf2 feedback loop. Conversely, in LNCaP cells, ALA exposure upregulated both SOD1 and p62 protein expression, but did not affect the KEAP1/Nrf2/p62 signaling pathway. In addition, wound-healing, Western blot, and immunofluorescence assays evidenced that ALA significantly reduced the motility of LNCaP and DU-145 cells and downregulated the protein expression of TGFβ1 and vimentin and the deposition of fibronectin. Finally, a soft agar assay revealed that ALA decreased the colony formation of both the prostate cancer cells by affecting the anchorage independent growth. Collectively, our in vitro evidence demonstrated that in prostate cancer cells, ALA reduces cell growth and counteracts both migration and invasion. Further studies are needed in order to achieve a better understanding of the underlined molecular mechanisms. Full article
(This article belongs to the Special Issue Bioactive Compounds and Therapeutic Targets in Prostate Cancer)
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14 pages, 4920 KiB  
Article
Combination of Kaempferol and Docetaxel Induces Autophagy in Prostate Cancer Cells In Vitro and In Vivo
by Qian Zhou, Gang Fang, Yuzhou Pang and Xueni Wang
Int. J. Mol. Sci. 2023, 24(19), 14519; https://doi.org/10.3390/ijms241914519 - 25 Sep 2023
Cited by 1 | Viewed by 1028
Abstract
Docetaxel is a first-line chemotherapy drug used to treat advanced prostate cancer, but patients who have used it often face the challenges of drug resistance and side effects. Kaempferol is a naturally occurring flavonol; our previous studies have confirmed that it has excellent [...] Read more.
Docetaxel is a first-line chemotherapy drug used to treat advanced prostate cancer, but patients who have used it often face the challenges of drug resistance and side effects. Kaempferol is a naturally occurring flavonol; our previous studies have confirmed that it has excellent anti-prostate activity. To investigate the anti-prostate cancer effects of docetaxel in combination with kaempferol, we conducted experiments at the cellular and whole-animal level. Plate cloning assays showed that the combination of docetaxel and kaempferol had a synergistic effect in inhibiting the proliferation of prostate cancer cells. The combination of these two compounds was found to induce autophagy in prostate cancer cells via transmission electron microscopy, and changes in the expression of autophagy-related proteins via Western blot assays also confirmed the occurrence of autophagy at the molecular level. We also confirmed the anti-prostate cancer effect of docetaxel in combination with kaempferol in vivo by establishing a mouse xenograft prostate cancer model. Autophagy-related proteins were also examined in mouse tumor tissues and verified the presence of autophagy in mouse tumor tissues. The above cellular and animal data suggest that docetaxel in combination with kaempferol has significant anti-prostate cancer effects and that it works by inducing autophagy in cells. Full article
(This article belongs to the Special Issue Bioactive Compounds and Therapeutic Targets in Prostate Cancer)
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15 pages, 3535 KiB  
Article
Neferine Targets the Oncogenic Characteristics of Androgen-Dependent Prostate Cancer Cells via Inducing Reactive Oxygen Species
by Subramanyam Dasari, Nishtha Pathak, Amy Thomas, Shreeja Bitla, Raj Kumar and Gnanasekar Munirathinam
Int. J. Mol. Sci. 2023, 24(18), 14242; https://doi.org/10.3390/ijms241814242 - 18 Sep 2023
Viewed by 1105
Abstract
Castration resistance poses a significant challenge in the management of advanced prostate cancer (PCa), with androgen deprivation therapy (ADT) or chemotherapy being the primary treatment options. However, these approaches often lead to significant side effects and the development of therapeutic resistance. Therefore, it [...] Read more.
Castration resistance poses a significant challenge in the management of advanced prostate cancer (PCa), with androgen deprivation therapy (ADT) or chemotherapy being the primary treatment options. However, these approaches often lead to significant side effects and the development of therapeutic resistance. Therefore, it is crucial to explore novel treatment options that can efficiently target PCa, improve patient survival, and enhance their quality of life. Neferine (Nef), a bioactive compound derived from plants, has emerged as a promising candidate for cancer treatment due to its ability to induce apoptosis, autophagy, and cell cycle arrest. In this study, we investigated the potential anticancer effects of Nef in androgen receptor (AR)-positive LNCaP and VCaP cells, representative models of androgen-dependent PCa. Our findings demonstrate that Nef effectively inhibits cell growth, proliferation, and the tumorigenic potential of androgen-dependent PCa cells. Furthermore, Nef treatment resulted in the excessive production of reactive oxygen species (ROS), leading to the activation of key markers of autophagy and apoptosis. These results suggest that Nef has the potential to target the oncogenic characteristics of androgen-dependent PCa cells by exploiting the potency of ROS and inducing autophagy and apoptosis in AR-positive PCa cells. These findings shed light on the therapeutic potential of Nef as a novel treatment option with reduced side effects for androgen-dependent prostate cancer. Further investigations are warranted to assess its efficacy and safety in preclinical and clinical settings. Full article
(This article belongs to the Special Issue Bioactive Compounds and Therapeutic Targets in Prostate Cancer)
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24 pages, 38971 KiB  
Article
Pyrogallol from Spirogyra neglecta Inhibits Proliferation and Promotes Apoptosis in Castration-Resistant Prostate Cancer Cells via Modulating Akt/GSK-3β/β-catenin Signaling Pathway
by Punnida Arjsri, Sariya Mapoung, Warathit Semmarath, Kamonwan Srisawad, Wirote Tuntiwechapikul, Supachai Yodkeeree and Pornngarm Dejkriengkraikul
Int. J. Mol. Sci. 2023, 24(7), 6452; https://doi.org/10.3390/ijms24076452 - 29 Mar 2023
Viewed by 1528
Abstract
Castration-resistant prostate cancer (CRPC) is an advanced form of prostate cancer associated with poor survival rates. The high proliferation and metastasis rates have made CRPC one of the most challenging types of cancer for medical practitioners and researchers. In this study, the anti-cancer [...] Read more.
Castration-resistant prostate cancer (CRPC) is an advanced form of prostate cancer associated with poor survival rates. The high proliferation and metastasis rates have made CRPC one of the most challenging types of cancer for medical practitioners and researchers. In this study, the anti-cancer properties and inhibition of CRPC progression by S. neglecta extract and its active constituents were determined using two CRPC cell lines, DU145 and PC3. The ethyl acetate fraction of S. neglecta (SnEA) was obtained using a solvent-partitioned extraction technique. The active constituents of SnEA were then determined using the HPLC technique, which showed that SnEA mainly contained syringic acid, pyrogallol, and p-coumaric acid phenolic compounds. After the determination of cytotoxic properties using the SRB assay, it was found that pyrogallol, but not the other two major compounds of SnEA, displayed promising anti-cancer properties in both CRPC cell lines. SnEA and pyrogallol were then further investigated for their anti-proliferation and apoptotic induction properties using propidium iodide and Annexin V staining. The results showed that SnEA and pyrogallol inhibited both DU145 and PC3 cell proliferation by inducing cell cycle arrest in the G0/G1 phase and significantly decreased the expression of cell cycle regulator proteins (cyclin D1, cyclin E1, CDK-2, and CDK-4, p < 0.001). SnEA and pyrogallol treatments also promoted apoptosis in both types of CRPC cells through significantly downregulating anti-apoptotic proteins (survivin, Bcl-2, and Bcl-xl, p < 0.001) and upregulating apoptotic proteins (cleaved-caspase-9, cleaved-caspase-3 and cleaved-PARP-1, p < 0.001). Mechanistic study demonstrated that SnEA and pyrogallol inactivated the Akt signaling pathway leading to enhancement of the active form of GSK-3β in CRPC cell lines. Therefore, the phosphorylation of β-catenin was increased, which caused degradation of the protein, resulting in a downregulation of β-catenin (unphosphorylated form) transcriptional factor activity. The current results reflect the potential impact of S. neglecta extract and pyrogallol on the management of castration-resistant prostate cancer. Full article
(This article belongs to the Special Issue Bioactive Compounds and Therapeutic Targets in Prostate Cancer)
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Review

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22 pages, 1029 KiB  
Review
Targeting Key Players of Neuroendocrine Differentiation in Prostate Cancer
by Irene Zamora, Michael R. Freeman, Ignacio J. Encío and Mirja Rotinen
Int. J. Mol. Sci. 2023, 24(18), 13673; https://doi.org/10.3390/ijms241813673 - 05 Sep 2023
Viewed by 1309
Abstract
Neuroendocrine prostate cancer (NEPC) is a highly aggressive subtype of prostate cancer (PC) that commonly emerges through a transdifferentiation process from prostate adenocarcinoma and evades conventional therapies. Extensive molecular research has revealed factors that drive lineage plasticity, uncovering novel therapeutic targets to be [...] Read more.
Neuroendocrine prostate cancer (NEPC) is a highly aggressive subtype of prostate cancer (PC) that commonly emerges through a transdifferentiation process from prostate adenocarcinoma and evades conventional therapies. Extensive molecular research has revealed factors that drive lineage plasticity, uncovering novel therapeutic targets to be explored. A diverse array of targeting agents is currently under evaluation in pre-clinical and clinical studies with promising results in suppressing or reversing the neuroendocrine phenotype and inhibiting tumor growth and metastasis. This new knowledge has the potential to contribute to the development of novel therapeutic approaches that may enhance the clinical management and prognosis of this lethal disease. In the present review, we discuss molecular players involved in the neuroendocrine phenotype, and we explore therapeutic strategies that are currently under investigation for NEPC. Full article
(This article belongs to the Special Issue Bioactive Compounds and Therapeutic Targets in Prostate Cancer)
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16 pages, 1301 KiB  
Review
Flavones: The Apoptosis in Prostate Cancer of Three Flavones Selected as Therapeutic Candidate Models
by Se Hyo Jeong, Hun Hwan Kim, Min Young Park, Pritam Bhagwan Bhosale, Abuyaseer Abusaliya, Chung Kil Won, Kwang Il Park, Eunhye Kim, Jeong Doo Heo, Hyun Wook Kim, Meejung Ahn, Je Kyung Seong and Gon Sup Kim
Int. J. Mol. Sci. 2023, 24(11), 9240; https://doi.org/10.3390/ijms24119240 - 25 May 2023
Viewed by 1772
Abstract
Cancer is a widespread but dangerous disease that can strike anyone and is the second 1leading cause of death worldwide. Prostate cancer, in particular, is a prevalent cancer that occurs in men, and much research is being done on its treatment. Although chemical [...] Read more.
Cancer is a widespread but dangerous disease that can strike anyone and is the second 1leading cause of death worldwide. Prostate cancer, in particular, is a prevalent cancer that occurs in men, and much research is being done on its treatment. Although chemical drugs are effective, they have various side effects, and accordingly, anticancer drugs using natural products are emerging. To date, many natural candidates have been discovered, and new drugs are being developed as drugs to treat prostate cancer. Representative candidate compounds that have been studied to be effective in prostate cancer include apigenin, acacetin and tangeretin of the flavone family among flavonoids. In this review, we look at the effects of these three flavones on prostate cancer cells via apoptosis in vitro and in vivo. Furthermore, in addition to the existing drugs, we suggest the three flavones and their effectiveness as natural anticancer agents, a treatment model for prostate cancer. Full article
(This article belongs to the Special Issue Bioactive Compounds and Therapeutic Targets in Prostate Cancer)
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12 pages, 2163 KiB  
Review
Sulforaphane and Its Protective Role in Prostate Cancer: A Mechanistic Approach
by James Mordecai, Saleem Ullah and Irshad Ahmad
Int. J. Mol. Sci. 2023, 24(8), 6979; https://doi.org/10.3390/ijms24086979 - 10 Apr 2023
Cited by 3 | Viewed by 3876
Abstract
The increasing incidence of prostate cancer worldwide has spurred research into novel therapeutics for its treatment and prevention. Sulforaphane, derived from broccoli and other members of the Brassica genus, is a phytochemical shown to have anticancer properties. Numerous studies have shown that sulforaphane [...] Read more.
The increasing incidence of prostate cancer worldwide has spurred research into novel therapeutics for its treatment and prevention. Sulforaphane, derived from broccoli and other members of the Brassica genus, is a phytochemical shown to have anticancer properties. Numerous studies have shown that sulforaphane prevents the development and progression of prostatic tumors. This review evaluates the most recent published reports on prevention of the progression of prostate cancer by sulforaphane in vitro, in vivo and in clinical settings. A detailed description of the proposed mechanisms of action of sulforaphane on prostatic cells is provided. Furthermore, we discuss the challenges, limitations and future prospects of using sulforaphane as a therapeutic agent in treatment of prostate cancer. Full article
(This article belongs to the Special Issue Bioactive Compounds and Therapeutic Targets in Prostate Cancer)
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