Scientists from South Korea evaluated the apoptotic mechanism of Vitex rotundifolia L. fruit extract against human colorectal cancer cells. Their findings were published in The American Journal of Chinese Medicine.
- The fruit of V. rotundifolia or beach vitex has been reported to induce apoptosis in human colorectal cancer cells through the accumulation of oxygen species.
- The researchers aimed to further understand the mechanisms of V. rotundifolia that induce apoptosis despite the fact that the molecular target for apoptosis has already been established.
- In this study, they showed a new potential mechanism for the relationship between V. rotundifolia-mediated ATF3 expression and apoptosis in human colorectal cancer cells.
- V. rotundifolia reduced cell viability and induced apoptosis, while increasing both protein and mRNA level of ATF3 and upregulated ATF3 promoted activity.
- The cis-element responsible for ATF3 transcriptional activation by V. rotundifolia was CREB which is located between -147 to -85 of ATF3 promoter.
- Inhibitions of ERK1/2, p38, JNK and GSK3-beta blocked V. rotundifolia-mediated ATF3 expression.
- ATF3 knockdown by ATF3 siRNA reduced the cleavage of PARP by V. rotundifolia, while ATF3 overexpression increased V. rotundifolia-mediated cleaved PARP. ATF3 knockdown also decreased V. rotundifolia-mediated cell viability and cell death.
- V. rotundifolia downregulated Bcl-2 expression at both protein and mRNA level. ATF3 knockdown by ATF3 siRNA blocked V. rotundifolia-mediated downregulation of Bcl-2.
Based on these findings, the researchers conclude that V. rotundifolia induces apoptosis in human colorectal cancer cells by activating ATF3 expression through transcriptional regulation and subsequently suppresses Bcl-2 expression as an anti-apoptotic protein.
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Journal Reference:
Song HM, Park GH, Koo JS, Jeong HJ, Jeong JB. VITEX ROTUNDIFOLIA FRUIT EXTRACT INDUCES APOPTOSIS THROUGH THE DOWNREGULATION OF ATF3-MEDIATED BCL-2 EXPRESSION IN HUMAN COLORECTAL CANCER CELLS. The American Journal of Chinese Medicine. 2017;45(04):901–915. DOI: 10.1142/s0192415x17500483