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Biomed Pharmacother. 2017 Aug;92:732-743. doi: 10.1016/j.biopha.2017.05.130. Epub 2017 Jun 4.

(-)-Kusunokinin and piperloguminine from Piper nigrum: An alternative option to treat breast cancer.

Author information

1
Department of Pharmacology, Faculty of Science, Prince of Songkla University, Songkhla 90110, Thailand.
2
Department of Chemistry, Faculty of Science, Prince of Songkla University, Songkhla 90110, Thailand.
3
Faculty of Science and Industrial Technology, Prince of Songkla University, Surat Thani Campus, Surat Thani 84000, Thailand.
4
Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand.
5
Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand; The Excellent Research Laboratory of Cancer Molecular Biology, Prince of Songkla University, Songkhla 90110, Thailand. Electronic address: gpotchan@medicine.psu.ac.th.

Abstract

Several studies have reported that active compounds isolated from Piper nigrum possess anticancer properties. However, there are no data on anticancer activity of (-)-kusunokinin and piperlonguminine. The purposes of this study were to isolate active compounds from P. nigrum and identify the molecular mechanisms underlying growth and apoptosis pathway in breast cancer cells. Two bioactive compounds, (-)-kusunokinin and piperlonguminine, were isolated from P. nigrum. Cytotoxicity and the molecular mechanism were measured by methyl thiazolyl tetrazolium (MTT) assay, flow cytometry and Western blot analysis. We found that the active compounds, which effect cancer cell lines were (-)-kusunokinin and piperlonguminine. These compounds have potent cytotoxic effects on breast cancer cells (MCF-7 and MDA-MB-468) and colorectal cells (SW-620). (-)-Kusunokinin demonstrated a cytotoxic effect on MCF-7 and MDA-MB-468 with IC50 values of 1.18 and 1.62μg/mL, respectively. Piperlonguminine had a cytotoxic effect on MCF-7 and MDA-MB-468 with IC50 values of 1.63 and 2.19μg/mL, respectively. Both compounds demonstrated lower cytotoxicity against normal breast cell lines with IC50 values higher than 11μg/mL. Cell cycle and apoptotic analysis using flow cytometry, showed that the (-)-kusunokinin and piperlonguminine induced cell undergoing apoptosis and drove cells towards the G2/M phase. Moreover, both compounds decreased topoisomerase II and bcl-2. The increasing of p53 levels further increased p21, bax, cytochrome c, caspase-8, -7 and -3 activities, except caspase-9. These results suggest that the (-)-kusunokinin and piperlonguminine have been shown to have potent anticancer activities through extrinsic pathway and G2/M phase arrest.

KEYWORDS:

(−)-kusunokinin; Anticancer; Breast cancer; Piper nigrum; Piperlonguminine

PMID:
28586745
DOI:
10.1016/j.biopha.2017.05.130
[Indexed for MEDLINE]

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