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Regulation of apoptosis in prostate cancer
S Gurumurthy1, K M Vasudevan, V M Rangnekar
1Graduate Center for Toxicology, University of Kentucky, Lexington, USA.
Abstract:
Transformation and malignant progression of prostate cancer is regulated by the inability of prostatic epithelial cells to undergo apoptosis rather than by increased cell proliferation. The basic apoptotic machinery of most prostate cancer cells is intact and the inability to undergo apoptosis is due to molecular alterations that result in failure to initiate or execute apoptotic pathways. This review discusses the role of anti-apoptotic proteins such as Bcl-2/BclXL, NF-kappaB, IGF, caveolin, and Akt, and pro-apoptotic molecules such as PTEN, p53, Bin1, TGF-beta, and Par-4 that can regulate progression of prostate cancer. In addition to highlighting the salient features of these molecules and their relevance in apoptosis, this review provides an appraisal of their therapeutic potential in prostate cancer. Molecular targeting of these proteins and/or their innate pro- or anti-apoptotic pathways, either singly or in combination, may be explored in conjunction with conventional and currently available experimental strategies for the treatment of both hormone-sensitive and hormone-resistant prostate cancer.
Insights
Prostate cancer progression stems from failed apoptosis, not rapid cell growth. Targeting key pro- and anti-apoptotic molecules offers new therapeutic strategies for hormone-sensitive and resistant prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Prostate cancer malignant progression is primarily driven by the failure of prostatic epithelial cells to undergo apoptosis, rather than increased cell proliferation.
- The fundamental apoptotic machinery in most prostate cancer cells remains functional, with defects arising from molecular alterations that impede apoptosis initiation or execution.
Purpose of the Study:
- To review the roles of specific anti-apoptotic proteins (Bcl-2/BclXL, NF-kappaB, IGF, caveolin, Akt) and pro-apoptotic molecules (PTEN, p53, Bin1, TGF-beta, Par-4) in regulating prostate cancer progression.
- To evaluate the therapeutic potential of targeting these apoptosis-regulating molecules in prostate cancer treatment.
Main Methods:
- Literature review of molecular mechanisms regulating apoptosis in prostate cancer.
- Analysis of the function and relevance of key pro- and anti-apoptotic proteins.
- Appraisal of therapeutic strategies targeting apoptosis pathways.
Main Results:
- Identified key anti-apoptotic proteins (Bcl-2/BclXL, NF-kappaB, IGF, caveolin, Akt) and pro-apoptotic molecules (PTEN, p53, Bin1, TGF-beta, Par-4) that influence prostate cancer progression.
- Highlighted the intact nature of basic apoptotic machinery and the role of molecular alterations in apoptosis failure.
- Discussed the therapeutic potential of targeting these molecules and their pathways.
Conclusions:
- Molecular targeting of pro- and anti-apoptotic pathways presents a promising therapeutic avenue for prostate cancer.
- Combined strategies targeting these pathways, alongside conventional treatments, may benefit both hormone-sensitive and hormone-resistant prostate cancer.
- Understanding the molecular basis of apoptosis resistance is crucial for developing effective prostate cancer therapies.