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Open AccessArticle

Fangchinoline, a Bisbenzylisoquinoline Alkaloid can Modulate Cytokine-Impelled Apoptosis via the Dual Regulation of NF-κB and AP-1 Pathways

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Department of Science in Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea
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Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
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Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
*
Authors to whom correspondence should be addressed.
Academic Editor: Maria da Graça Costa G. Miguel
Molecules 2019, 24(17), 3127; https://doi.org/10.3390/molecules24173127
Received: 1 August 2019 / Revised: 24 August 2019 / Accepted: 27 August 2019 / Published: 28 August 2019
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
Fangchinoline (FCN) derived from Stephaniae tetrandrine S. Moore can be employed to treat fever, inflammation, rheumatism arthralgia, edema, dysuria, athlete’s foot, and swollen wet sores. FCN can exhibit a plethora of anti-neoplastic effects although its precise mode of action still remains to be deciphered. Nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) can closely regulate carcinogenesis and thus we analyzed the possible action of FCN may have on these two signaling cascades in tumor cells. The effect of FCN on NF-κB and AP-1 signaling cascades and its downstream functions was deciphered using diverse assays in both human chronic myeloid leukemia (KBM5) and multiple myeloma (U266). FCN attenuated growth of both leukemic and multiple myeloma cells and repressed NF-κB, and AP-1 activation through diverse mechanisms, including attenuation of phosphorylation of IκB kinase (IKK) and p65. Furthermore, FCN could also cause significant enhancement in TNFα-driven apoptosis as studied by various molecular techniques. Thus, FCN may exhibit potent anti-neoplastic effects by affecting diverse oncogenic pathways and may be employed as pro-apoptotic agent against various malignancies. View Full-Text
Keywords: fangchinoline; NF-κB; AP-1; cancer; apoptosis fangchinoline; NF-κB; AP-1; cancer; apoptosis
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Jung, Y.Y.; Shanmugam, M.K.; Chinnathambi, A.; Alharbi, S.A.; Shair, O.H.; Um, J.-Y.; Sethi, G.; Ahn, K.S. Fangchinoline, a Bisbenzylisoquinoline Alkaloid can Modulate Cytokine-Impelled Apoptosis via the Dual Regulation of NF-κB and AP-1 Pathways. Molecules 2019, 24, 3127.

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