| Summary: | 碩士 === 慈濟大學 === 生命科學系碩士班 === 107 === Prostate cancer is the second most frequent cancer and the sixth
among the top ten cancer leading cause of death in men. An anthraquinone
derivative, ANT, exhibits anticancer activity and elicits autophagy on
prostate cancer cells in our previous study. Herein, we comparatively
investigate the molecular mechanism of this novel compound on prostate
cancer cells by PC-3 and DU145 cells. We found that the highly expressed SIRT1, a NAD+-dependent deacetylase of the Sirtuin family, was declined
in both prostate cancer cells. To clarify the effects of ANT on autophagy
and the underlying mechanisms in these human prostate cancer cells, the
SIRT1-regulated cell death pathway was investigated in this study. It
showed that ANT induces autophagy with both the concentration- and
time-dependent manner in PC-3 and DU145 cells through inhibiting the
mammalian target of rapamycin (mTOR) to induce autophagic cell death.
On the other hand, SIRT1 activator, but not SIRT1 inhibitor, enhanced the
ANT-induced cell death. ANT downregulated the expression of SIRT1, and
autophagy was enhanced while the SIRT1 was inhibited. Moreover,
silencing of SIRT1 expression by SIRT1-siRNA also suppressed cell
proliferation in both PC-3 and DU145 cells. Our findings indicate that ANT
inhibits prostate cancer proliferation and migration and induces autophagy
via SIRT1- and mTOR-mediated pathways.
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