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

Abstract

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.

• Authors: Hyo-Jin Kim, Bo-Gyeong Seo, Kwang Dong Kim, Jiyun Yoo, Joon-Hee Lee, Byung-Sun Min, Jeong-Hyung Lee, Cheol Hwangbo
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 4 (Feb 14 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 32075108 (Publication Type: Journal Article)

Chemical References

• Alkaloids
• BCL2 protein, human
• CASP8 and FADD-Like Apoptosis Regulating Protein
• FADD protein, human
• Fas-Associated Death Domain Protein
• Proto-Oncogene Proteins c-bcl-2
• Caspase 8

Topics

• Alkaloids (chemistry, pharmacology)
• Apoptosis (drug effects)
• CASP8 and FADD-Like Apoptosis Regulating Protein (genetics, metabolism)
• Caspase 8 (metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Fabaceae (chemistry, metabolism)
• Fas-Associated Death Domain Protein (metabolism)
• Humans
• Lung Neoplasms (metabolism, pathology)
• Lymphoma (metabolism, pathology)
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)