Open Access2-Amino-nicotinamide induces apoptosis of prostate cancer cells via inhibition of PI3K/AKT and phosphorylation of STA3/JAK2
Author(s) -
Junhui Ying,
Changchun Zhou,
Yi Jin,
Daqiao Lu,
Bing Xiong,
Jiahui Wei
Publication year - 2020
Publication title -
tropical journal of pharmaceutical research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.209
H-Index - 36
eISSN - 1596-5996
pISSN - 1596-9827
DOI - 10.4314/tjpr.v19i9.10
Subject(s) - lncap , nicotinamide , apoptosis , protein kinase b , chemistry , pi3k/akt/mtor pathway , cancer research , cytotoxicity , viability assay , microbiology and biotechnology , cancer cell , biochemistry , biology , cancer , in vitro , genetics , enzyme
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-aminonicotinamide, 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