Aman Tedasen, Sirinapa Dokduang, Yaowapa Sukpondma, Varomyalin Tipmanee, Narissara Lailerd and Potchanapond Graidist
Prince of Songkla University, Thailand
Scientific Tracks Abstracts: Pharm Anal Acta
Introduction & Objective: (-)-Kusunokinin, a lignan compound, which extracted from Piper nigrum, showed similar chemical structure with etoposide, a chemotherapeutic drug. This compound has a potent cytotoxic effect on breast cancer cell lines through the inhibition of cell cycle progression at G2/M phase, reduction of topoisomerase II and bcl-2 and promotion of p53, p21, bax, cytochrome c, caspase-8, caspase-7 and caspase-3. This current study aims to isolate (-)-kusunokinin from a large scale (22 kg) of black pepper seeds, identify (-)-kusunokinin targeted protein and investigate the anti-cancer activity in mammary tumorigenesis rats.
Method: Firstly, breast (MCF-7, MDA-MB-468 and MDA-MB-231), colon (SW-620 and HT-29) and lung (A-549) cancer cell lines were treated with (-)-kusunokinin to determine the cytotoxic activity using MTT assay.
Result: The result showed that (-)-kusunokinin strongly inhibited MCF-7 and HT-29 cells with IC50 values of 3.08±0.39 and 3.59±0.53 μM more than etoposide. In addition, (-)-kusunokinin showed less cytotoxic to normal L-929 cells with IC50 values of 69.40±0.87 μM. Then, the molecular docking analysis showed inhibitory effect of (-)-kusunokinin against FMS kinase protein with strong binding energy value of -11.53 kcal mol-1 and inhibition constant value of 3.54 nM, which better than pexidartinib, a FMS known inhibitor. Finally, (-)-kusunokinin at dose 7.0 mg/kg.BW, 14.0 mg/kg.BW and combination of 7.0 mg/kg.BW (-)-kusunokinin with 0.5 mg/kg.BW doxorubicin induced cell death in tumor tissues and caused tumor inhibition with the suppression rate at 56.1, 68.9 and 82.9% respectively. Moreover, (-)-kusunokinin reduced cancer progression through down-regulation of c-myc, CDK1 and cyclin B1 proteins.
Conclusion: In conclusion, our data suggest that (-)-kusunokinin could bind to FMS kinase receptor protein and regulated cellular proliferation and cell cycle in breast cancer cells and rat models.
1. Srisawat T, Sukpondma Y, Chimplee S, Kanokwiroon K, Tedasen A, Graidist P (2014) Extracts from Vatica diospyroides type SS fruit show low dose activity against MDA-MB-468 breast cancer cell line via apoptosis action. Bio Med Research International; article id: 479602.
2. Sriwiriyajan S, Tedasen A, Lailerd N, Boonyaphiphat P, Nitiruangjarat A, Yan D, Graidist P (2016) Anti-cancer and cancer preventive effects of a piperine free Piper nigrum extract on N-nitrosomethylurea induced mammary tumorigenesis in rats. Cancer Prev Res; 9: 74-82.
Aman Tedasen is currently working as a Post-doctoral Researcher at Prince of Songkla University, Thailand. His research interest has focused on developing effective treatment strategies from herbal medicine for breast cancer.
E-mail: [email protected]