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Virosecurinine induces apoptosis by affecting Bcl-2 and Bax expression in human colon cancer SW480 cells
Chuan-Rong Chen1, Yong-Hui Xia, Shu-Yan Yao
1Department of Oncology, Wannan Medical College, Wuhu, China.
Abstract:
Virosecurinine, the major alkaloid isolated from Securinega suffruticosa Pall Rehd was found to exhibit growth inhibition and cytotoxicity against huaman colon cancer SW480 cells via the microculture tetrazolium (MTT) assay. Due to its greater cytotoxic potency and selectivity towards SW480 cells, flow cytometry was used to analyze the cell cycle distribution of control and treated SW480 cells whereas Annexin V-FITC/PI flow cytometry analysis was carried out to confirm apoptosis induced by virosecurinine in SW480 cells. Apoptotic regulatory genes were determined by RT-PCR analysis. Virosecurinine was found to induce G1/S cell cycle arrest which led to predominantly apoptotic mode of cell death. Mechanistically, virosecurinine was found to up-regulated the Bax gene expression and down-regulated the Bcl-2 expression in SW480, The ratio of Bcl-2 to Bax was significantly decreased. Hence, we suggest that virosecurinine induced apoptosis in SW480 cells by affecting the expression of bcl-2 and bax.
Insights
Virosecurinine, a natural alkaloid, effectively inhibits human colon cancer SW480 cell growth and induces apoptosis. It achieves this by causing G1/S cell cycle arrest and altering apoptotic gene expression, specifically Bax and Bcl-2.
Area of Science:
- Natural Product Chemistry
- Cancer Biology
- Molecular Pharmacology
Background:
- Securinega suffruticosa Pall Rehd yields virosecurinine, a major alkaloid.
- Colon cancer remains a significant global health concern, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate the anti-cancer effects of virosecurinine on human colon cancer SW480 cells.
- To elucidate the underlying mechanisms of virosecurinine-induced cell death.
Main Methods:
- Microculture tetrazolium (MTT) assay for cytotoxicity assessment.
- Flow cytometry for cell cycle distribution and apoptosis analysis (Annexin V-FITC/PI).
- Reverse transcription-polymerase chain reaction (RT-PCR) for apoptotic gene expression profiling.
Main Results:
- Virosecurinine demonstrated significant growth inhibition and cytotoxicity against SW480 cells.
- Virosecurinine induced G1/S cell cycle arrest, leading to apoptosis.
- Upregulation of Bax and downregulation of Bcl-2 expression were observed, decreasing the Bcl-2/Bax ratio.
Conclusions:
- Virosecurinine effectively induces apoptosis in human colon cancer SW480 cells.
- The mechanism involves G1/S cell cycle arrest and modulation of Bcl-2 and Bax gene expression.
- Virosecurinine shows potential as a therapeutic agent for colon cancer.
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