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Open AccessArticle

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

1
Division of Life Science, College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea
2
Division of Applied Life Science (BK21 Plus), PMBBRC and Research institute of Life Sciences, Geongsang National University, Jinju 52828, Korea
3
Department of Animal Bioscience, College of Agriculture and Life Sciences, Gyeongsang National University, Jinju 52828, Korea
4
College of Pharmacy, Catholic University of Daegu, Daegu 38430, Korea
5
Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(4), 1298; https://doi.org/10.3390/ijms21041298
Received: 22 January 2020 / Revised: 8 February 2020 / Accepted: 12 February 2020 / Published: 14 February 2020
(This article belongs to the Section Molecular Biology)
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.
Keywords: C5 (3β-Acetyl-nor-erythrophlamide); apoptosis; extrinsic pathways; Bcl-2; caspase-8 C5 (3β-Acetyl-nor-erythrophlamide); apoptosis; extrinsic pathways; Bcl-2; caspase-8
MDPI and ACS Style

Kim, H.-J.; Seo, B.-G.; Kim, K.D.; Yoo, J.; Lee, J.-H.; Min, B.-S.; Lee, J.-H.; Hwangbo, C. C5, A Cassaine Diterpenoid Amine, Induces Apoptosis via the Extrinsic Pathways in Human Lung Cancer Cells and Human Lymphoma Cells. Int. J. Mol. Sci. 2020, 21, 1298.

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