Purpose: Gastric carcinoma is the fourth principal cause of cancer-related deaths throughout the globe. There are inadequate clinical therapies for gastric cancer due to lack of operational drugs and ambiguity in molecular mechanisms. As such there is a persistent requirement for novel and effective anticancer drugs for gastric cancer. The main purpose of the current study was to investigate the antitumor effects of a plant diterpenoid, namely Oridonin, against SGC-7901 human gastric cancer cells along with examining its effects on cellular apoptosis, cell autophagy and cell cycle phase distribution.
Methods: WST-1 cell proliferation assay was used to evaluate cell viability of SGC-7901 human gastric cancer cells. Apoptosis was evaluated by using DAPI and comet assays using fluorescence microscopy. Autophagy was evaluated by transmission electron microscopy (TEM) and western blot method. Effects on cell cycle phase distribution were studied by flow cytometry.
Results: Oridonin molecule led to considerable and dose-dependent antiproliferative effects on SGC-7901 human gastric cancer cells exerting only mild cytotoxic effects in normal cells thus exhibiting selective toxicity. The number of gastric cancer cell colonies decreased significantly as oridonin dose increased. DAPI and comet assays revealed that oridonin induced powerful apoptotic effects in these cells, triggering significant DNA damage and both these effects exhibited dose-dependence. TEM indicated that oridonin induced autophagy in SGC-7901 cells by creating autophagosomes and autophagic vacuoles. Oridonin also targeted G2/M phase cell cycle in these gastric cancer cells along with targeting some key cell cycle related proteins including cyclin-B1, cyclin D1 and cyclin E.
Conclusion: In conclusion, the results show that oridonin showed strong anticancer effects in SGC-7901 human gastric cancer cells by triggering apoptosis and autophagy, and targeting cell cycle at G2/M phase.
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