Page 56 - F. Cell biology

[F. Cell biology-32]

Targeting both apoptosis and necroptosis by resveratrol and

docetaxel induces synergistic cytotoxicity of prostate

carcinoma cells

Sang-Han Lee¹, Yoon-Jin Lee¹

¹Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan 31151, Republic of Korea

The current study was conducted to investigate the efficacy of resveratrol in combination with the anticancer drug
docetaxel in inducing cell death in prostate carcinoma LNCaP cells, including factors involved in detailed cell death
mechanisms. Using 2D monolayer and 3D spheroid culture systems, the effects of resveratrol and docetaxel on cell

viability, ROS levels, mitochondrial function, apoptosis and necroptosis were investigated by MTT, flow cytometry
and Western blotting analysis. At concentrations not toxic to normal prostate epithelial HPrEC cells, resveratrol

significantly inhibited the viability of LNCaP cells. Combination treatment with resveratrol and docetaxel
synergistically inhibited cytotoxicity, as demonstrated by an increase in sub-G0/G1 peak, annexin V-PE positive cells,

ROS levels, loss of mitochondrial membrane potential, and upregulation of mediators for DNA damage response,
apoptosis, and necroptosis. In conclusion, we report resveratrol as an adjunct drug to improve the outcome of

treatment in docetaxel therapy. Although the underlying mechanisms of necroptosis in cancer therapy should be
comprehensively investigated, targeting apoptosis and necroptosis simultaneously can provide a strategy to develop

a therapeutic agent for apoptosis-resistant carcinoma.