C5, A Cassaine Diterpenoid Amine, Induces Apoptosis via the Extrinsic Pathways in Human Lung Cancer Cells and Human Lymphoma Cells

International Journal of Molecular Sciences

Byung-Sun Min¹  Joon-Hee Lee²  Jeong-Hyung Lee³  Jiyun Yoo⁴  Bo-Gyeong Seo⁴  Cheol Hwangbo⁴  Hyo-Jin Kim⁴  KwangDong Kim⁴ 

[1] College of Pharmacy, Catholic University of Daegu, Daegu 38430, Korea;Department of Animal Bioscience, College of Agriculture and Life Sciences, Gyeongsang National University, Jinju 52828, Korea;Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Korea;Division of Life Science, College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea;

关键词: c5 (3β-acetyl-nor-erythrophlamide);    apoptosis;    extrinsic pathways;    bcl-2;    caspase-8;   

DOI  :  10.3390/ijms21041298

来源: DOAJ

【 摘 要 】

Apoptosis pathways in cells are classified into two pathways: the extrinsic pathway, mediated by binding of the ligand to a death receptor and the intrinsic pathway, mediated by mitochondria. Apoptosis is regulated by various proteins such as Bcl-2 (B-cell lymphoma 2) family and cellular FLICE (Fas-associated Death Domain Protein Interleukin-1β-converting enzyme)-inhibitory protein (c-FLIP), which have been reported to inhibit caspase-8 activity. In this study, it was found that C5 (3β-Acetyl-nor-erythrophlamide), a compound of cassaine diterpene amine from Erythrophleum fordii, induced cell apoptosis in a variety of types of cancer cells. Induction of apoptosis in cancer cells by C5 was inversely related to the level of Bcl-2 expression. Overexpression of Bcl-2 into cancer cells significantly decreased C5-induced apoptosis. It was also found that treatment of cancer cells with a caspase-8 inhibitor significantly suppressed C5-induced apoptosis; however, treatment with caspase-9 inhibitors did not affect C5-induced apoptosis, suggesting that C5 may induce apoptosis via the extrinsic pathway by activating caspase-8. It was confirmed that treatment with C5 alone induced an association of FADD with procaspase-8; however, overexpression of c-FLIP decreased C5-induced caspase-8 activation. In conclusion, C5 could be utilized as a new useful lead compound for the development of an anti-cancer agent that has the goal of apoptosis.

【 授权许可】

Unknown