Zhi Yu, WuJimu , Juan Guo, Weibin Li and Jun Tian
Background and Objective: Plant-derived phytocompounds may be useful in the treatment of cancer, because of their high efficiency, cheap cost and few side effects. Here the inhibitory activity of Zeylenone (Zey) on colon carcinoma (HCT-116) cells and explored the possible underlying mechanisms of cancer cell death. Materials and Methods: HCT-116 cells were treated by Zey in various dosages and cell cytotoxicity was studied using MTT analysis. Oxidative-stress mediated cell death was confirmed by the analysis of ROS generation and mitochondrial membrane potential alteration in HCT-116 cells. Furthermore, Zey treatment mediated apoptotic, cell proliferation and metastatic protein expression was measured by western blot analysis. Results: Current findings enumerated that Zey treatment effectively reduced HCT-116 when evaluated with control cells by the maximum inhibitory result at a dosage of 15 μM. The apoptotic effect of Zey induced generation of ROS thus leads to loss of mitochondrion membrane potential and nuclear fragmentation was found. Nuclear factor-kappa B (NF-κB) concern as a main transcriptional factor and its overexpression regulate several proliferative, apoptotic and metastatic proteins in response to a cancerous condition. Inhibition of these NF-κB activities has been considered a vital target for suppressing colon cancer cell growth. In this study, Zey treatment suppresses the growth of cell proliferative and metastatic markers such as TNF-α, cyclin D1, PCNA, MMP-2, MMP-9 and Bcl-2 through the downregulation of NF-κB and IκBα in HCT-116. Moreover, Zey mediated inhibition of NF-κB subsequently induces the proapoptotic genes (Bax, cytochrome-c, caspase-9 and caspase-3) expressions in HCT-116 cells. Conclusion: Zey treatments considerably inhibit proliferation, metastasis and induces apoptosis, probably by controlling NF-κB signalling in colon cancer cells.
Zhi Yu, WuJimu , Juan Guo, Weibin Li and Jun Tian, 2022. Zeylenone from Uvaria grandiflora Roxb. Induces Apoptosis in Colon Cancer Cells Through Suppression of NF-κB Signalling. International Journal of Pharmacology, 18: 190-198.