Androgen receptor (AR) positive vs negative roles in prostate cancer cell deaths including apoptosis, anoikis, entosis, necrosis and autophagic cell death

Abstract

Androgen/androgen receptor (AR) signaling plays pivotal roles in the prostate development and homeostasis as well as in the progression of prostate cancer (PCa). Androgen deprivation therapy (ADT) with anti-androgens remains as the main treatment of PCa, and it has been shown to effectively suppress PCa growth during the first 12–24 months. However, ADT eventually fails and tumors may re-grow and progress into the castration resistant stage. Recent reports revealed that AR might play complicated and even opposite roles in PCa progression that might depend on cell types and tumor stages. Importantly, AR may influence PCa progression via differential modulation of various cell deaths including apoptosis, anoikis, entosis, necrosis, and autophagic cell deaths. Targeting AR may induce PCa cell apoptosis, autophagic cell deaths and programmed necrosis, yet targeting AR may also suppress cell deaths via anoikis and entosis that may potentially lead to increased metastasis. These differential functions of AR in various types of PCa cell death might challenge the current ADT with anti-androgens treatment. Further detailed dissection of molecular mechanisms by which AR modulates different PCa cell deaths will help us to develop a better therapy to battle PCa.

Castration impairs erectile organ structure and function by inhibiting autophagy and promoting apoptosis of corpus cavernosum smooth muscle cells in rats

“…Androgens and the androgen receptor (AR) suppress or promote apoptosis and or autophagy [45]. Based on our findings and other reports [9,15,[44][45][46][47], we speculated that androgen can affect the counter-regulation of autophagy and apoptosis in CCSMCs, mainly by regulating the BECN 1-Bcl-2 interaction.…”

Involvement of NF-ΚB and HSP70 signaling pathways in the apoptosis of MDA-MB-231 cells induced by a prenylated xanthone compound, α-mangostin, from Cratoxylum arborescens

“…The growth of cells is moderated by cell proliferation (division) and apoptosis (programmed cell death),66 and homeostasis is sustained by a balance between the two. One key characteristic of cancer cells is the absence of the homeostasis process, therefore dietary management of this process may result in a deeper understanding regarding cancer prevention 67.…”

MtDNA depleted PC3 cells exhibit Warburg effect and cancer stem cell features

“…It is also known that both invasion capacity and anoikis resistance are highly related to cancer cell stemness [46–49]. PCa, like all other carcinomas, is composed of a mixture of cells in various differentiation grades, representing different degrees of stem/progenitor cell phenotypes [50]. Thus, the use of tumor samples for correlation studies of mitochondrial function and cancer cell stemness is a challenge.…”