Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

2-Amino-nicotinamide induces apoptosis of prostate cancer cells via inhibition of PI3K/AKT and phosphorylation of STA3/JAK2

Junhui Ying , Changchun Zhou, Yili Jin, Daqiao Lu, Bing Xiong, Jiahui Wei

Department of Urology Surgery, Dongyang People's Hospital Affiliated to Wenzhou Medical University, Dongyang, Zhejiang 322100, China;

For correspondence:- Junhui Ying Email: JakobTapiaolc@yahoo.com Tel:+8657886856101

Accepted: 27 August 2020 Published: 30 September 2020

Citation: Ying J, Zhou C, Jin Y, Lu D, Xiong B, Wei J. 2-Amino-nicotinamide induces apoptosis of prostate cancer cells via inhibition of PI3K/AKT and phosphorylation of STA3/JAK2. Trop J Pharm Res 2020; 19(9):1863-1869 doi: 10.4314/tjpr.v19i9.10

© 2020 The authors.
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Abstract

Purpose: To study the cytotoxicity of 2-amino-nicotinamide against prostate cancer (PCa) cells, and the underlying molecular mechanism.

Methods: The effect of 2-amino-nicotinamide on cell viability and apoptosis was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) and flow cytometry, respectively, while its effect on cellular production of fluorescent?oxidized product from DCFH?DA was measured using flow cytometry. Apoptosis-related protein expressions were evaluated by western blot assay.

Results: 2-Amino-nicotinamide produced cytotoxicity against MCF-7, SGC7901, PCa 22Rv1 and LNCaP cancer cell lines (p < 0.05). Mechanistic data revealed that 2-amino-nicotinamide activated apoptosis, and enhanced cleavage of PARP and caspase?3 in PCa 22Rv1 and LNCaP cells. In PCa 22Rv1 and LNCaP cell lines, cytochrome C and Bax levels were enhanced by treatment with 2-amino-nicotinamide, while Bcl?2 protein level was suppressed (p < 0.05). Activated expressions of PI3K, Akt and ERK in PCa 22Rv1 and LNCaP cells were down-regulated, while p38 expression was increased. Moreover, 2-amino-nicotinamide suppressed the activation of JAK2 and STAT3, but did not alter total JAK2 and STAT3 levels in PCa 22Rv1 and LNCaP cells (p < 0.05).

Conclusion: 2-Amino-nicotinamide exerts cytotoxic effects on prostate carcinoma cells via activation of apoptosis and down-regulation of PI3K/AKT and STA3/JAK2. Thus, 2-amino nicotinamide is a potential bioactive agent for prostate cancer management.

Keywords: 2-Amino-nicotinamide, Apoptosis, Fluorescent?oxidized, Cytotoxicity