Novel quercetin derivative TEF induces ER stress and mitochondria-mediated apoptosis in human colon cancer HCT-116 cells

Although quercetin is very well known for its anticancer activity, however it shows some drawbacks. Herein, we have evaluated the apoptotic effect TEF (5, 3′-dihydroxy-3, 7, 4′-triethoxyflavone), a newly synthesized quercetin derivative on HCT-116 colon cancer cells. After 24 h of treatment, the proliferation of colon cancer cells was inhibited by TEF. TEF induced apoptosis, as confirmed by the presence of fragmented nuclei, reduced mitochondrial membrane potential, and elevated cytoplasmic and mitochondrial reactive oxygen species (ROS) levels. TEF treatment causes elevation of IRE1-α and activates calcium ions (Ca²⁺) with concomitant increase in JNK levels. Elevated Ca²⁺ ion translocates from ER to mitochondria which leads to ROS release and oxidative stress. TEF treatment further elevated levels of pro-apoptotic factors and down-regulated the level of Bcl2. TEF led to activation of mito-JNK (mitochondrial JNK), which plays a crucial role in activation of oxidative stress and caspase mediated apoptotic cell death. Moreover, JNK inhibition shown to suppress TEF induced apoptosis in HCT-116 colon cancer cells. Therefore, this study reveals the apoptotic role of TEF against HCT-116 cell line via IRE1-α and mito-JNK pathway.