SIRT3 determines the sensitivity of cancer cells to mitochondrial targeting
TL;DR
The data demonstrate that SIRT3 does not play a major role in cancer cell death induced by the conventional chemotherapeutic drug cisplatin but exerts a protective role in the case of the mitochondria-targeting agent α-TOS.
Abstract
SIRT3 is a mitochondria-localized member of the sirtuin family, playing a key role in cellular antioxidant defense. Its function in carcinogenesis and therapy response remains uncertain. In the present study, we sought to identify the role of SIRT3 in regulating cell death induced by conventional DNA-damaging anticancer drugs or mitochondria-targeting compounds using bioinformatic analysis, western blot analysis, viability, and clonogenic assays. High SIRT3 levels were associated with higher sensitivity to DNA-damaging cisplatin and resistance to mitochondria-targeted α-tocopheryl succinate (α-TOS) in non-small cell lung cancer, ovarian cancer, and neuroblastoma cells. SIRT3 overexpression, knockout, or knockdown did not influence the sensitivity of cancer cells to cisplatin. SIRT3 depletion in cells with high basal SIRT3 levels decreased the viability and clonogenic capacity of cells after α-TOS treatment without triggering apoptosis. SIRT3 overexpression in cells with low basal SIRT3 levels increased viability and decreased accumulation of apoptotic markers after α-TOS treatment. Collectively, our data demonstrate that SIRT3 does not play a major role in cancer cell death induced by the conventional chemotherapeutic drug cisplatin but exerts a protective role in the case of the mitochondria-targeting agent α-TOS.