cytochrome-c-t and alpinetin

Alpinetin is a natural flavonoid widely distributed in Zingiberaceae. Previous studies have demonstrated that alpinetin markedly inhibits tumour growth. However, the molecular mechanisms underlying the antitumour effects of alpinetin are unclear. Bcl‑2‑associated X protein (Bax) translocation is known to activate the mitochondrial‑dependent endogenous apoptosis pathway. The aim of the current study was to investigate the roles of Bax and the mitochondrial pathway during alpinetin‑induced gastric cancer cell apoptosis and the effects of alpinetin on the cell cycle. Human gastric cancer cells were treated with various doses of alpinetin and an MTT assay was performed to measure cell viability, flow cytometry to measure the apoptotic rate, changes in the cell cycle and mitochondrial membrane potential and western blot analysis to detect the expression levels of relevant proteins. Results demonstrate that alpinetin induces apoptosis in human gastric cancer cells in a dose‑ and time‑dependent manner. During the early stages of apoptosis, alpinetin may alter mitochondrial membrane potential leading to release of cytochrome c from mitochondria, activation of caspase family members and ultimately apoptosis of human gastric cancer cells. Results of the present study indicate that alpinetin‑induced human gastric cancer cell apoptosis is associated with the mitochondrial pathway.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; bcl-2-Associated X Protein; Caspases; Cell Line, Tumor; Cytochromes c; Flavanones; G2 Phase Cell Cycle Checkpoints; Humans; M Phase Cell Cycle Checkpoints; Membrane Potential, Mitochondrial; Mitochondria; Stomach Neoplasms; Zingiberaceae

Alpinetin is a novel plant flavonoid derived from Alpinia katsumadai Hayata, found to possess strong anticancer effects. However, the antitumor effect of alpinetin on pancreatic cancer cells and the detailed mechanism remain unclear. The aim of this study was to investigate alpinetin's beneficial effect on pancreatic cancer and the possible molecular mechanism involved. Pancreatic cancer cell lines were treated with alpinetin at various doses and for different times, and the effect of alpinetin on cell growth inhibition, apoptosis and the cell cycle was determined. The expression of Bcl-2, Bcl-xL, XIAP and Bax, the activity of caspases and the levels of cytochrome c released were measured. The results showed that alpinetin inhibited the viability of three pancreatic cancer cell lines and induced apoptosis of BxPC-3 cells in a dose- and time-dependent manner. This was accompanied by regulation of the expression of Bcl-2, Bcl-xL, Bax and XIAP. Furthermore, alpinetin treatment led to the release of cytochrome c and activation of caspases-3, -8 and -9 proteins. Taken together, our studies indicate that alpinetin inhibited the proliferation of pancreatic cancer cells possibly through the regulation of the Bcl-2 family and XIAP expression, release of cytochrome c and the activation of caspases. Alpinetin may serve as a potential agent for the development of pancreatic cancer cell therapies.

Topics: Apoptosis; bcl-2-Associated X Protein; bcl-X Protein; Caspase 3; Caspase 8; Caspase 9; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cytochromes c; Flavanones; Gene Expression Regulation, Neoplastic; Humans; Pancreatic Neoplasms; X-Linked Inhibitor of Apoptosis Protein