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

Abstract

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.

• Authors: Young Yun Jung, Muthu K Shanmugam, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Omar H M Shair, Jae-Young Um, Gautam Sethi, Kwang Seok Ahn
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 24 Issue 17 (Aug 28 2019) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 31466313 (Publication Type: Journal Article)

Chemical References

• Benzylisoquinolines
• NF-kappa B
• TNF protein, human
• Transcription Factor AP-1
• Tumor Necrosis Factor-alpha
• fangchinoline
• I-kappa B Kinase

Topics

• Benzylisoquinolines (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Drug Screening Assays, Antitumor
• Humans
• I-kappa B Kinase (metabolism)
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, metabolism)
• Multiple Myeloma (drug therapy, metabolism)
• NF-kappa B (metabolism)
• Phosphorylation (drug effects)
• Signal Transduction (drug effects)
• Transcription Factor AP-1 (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)