Peanut testa extracts enhance anticancer effect of cisplatin against human cholangiocarcinoma cells via modulation of histone deacetylase inhibitory activity

Somprasong Saenglee; Gulsiri Senawong; Jarckrit Jeeunngoi; Thanaset Senawong; Sanun Jogloy; Albert Ketterman; Banchob Sripa; Thanaset Senawong

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Peanut testa extracts enhance anticancer effect of cisplatin against human cholangiocarcinoma cells via modulation of histone deacetylase inhibitory activity

Author: Somprasong SAENGLEE ¹ ; Gulsiri SENAWONG ¹ ; Jarckrit JEEUNNGOI ¹ ; Thanaset SENAWONG ¹ ; Sanun JOGLOY ² ; Albert KETTERMAN ³ ; Banchob SRIPA ⁴ ; Thanaset SENAWONG ⁵
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1. Department of Biochemistry, Faculty of Science, Khon Kaen University
2. Department of Plant Science and Agricultural Resources, Faculty of Agriculture, Khon Kaen University
3. Institute of Molecular Biosciences, Mahidol University
4. Department of Pathology, Faculty of Medicine, Khon Kaen University
5. Natural Product Research Unit, Faculty of Science, Khon Kaen University
Publication Type:Journal Article
Keywords: Apoptosis; Caspases; Cholangiocarcinoma; Cisplatin; Natural histone deacetylase inhibitor; Peanut testa extracts
From:Asian Pacific Journal of Tropical Biomedicine 2020;10(8):369-378
CountryChina
Language:Chinese
Abstract: Objective: To investigate the effect of combination treatments of cisplatin and KK4 and ICG15042 peanut testa extracts against cholangiocarcinoma cells in vitro. Methods: The growth inhibition, cell cycle arrest and apoptosis of cholangiocarcinoma cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry analysis, respectively. The levels of proteins involved in apoptosis were assessed using Western blotting assays. The caspase activity was assessed using a colorimetric caspase activity assay. Results: Cisplatin and peanut (KK4 and ICG15042) testa extracts inhibited the growth of cholangiocarcinoma cell lines (KKU-M214 and KKU-100 cells) in a dose- A nd time-dependent manner. The combination treatments reduced cell viability and induced apoptosis of cholangiocarcinoma cells more efficiently than singledrug treatments. Cancer cell death synergistically mediated by cisplatin and peanut testa extracts was observed in KKU-M214 cells (combination index < 1.0) but not in KKU-100 cells (combination index > 1.0). The combination treatments also increased the sub-G1 population and caused KKU-M214 cell cycle arrest at S and G2/M phases, which were the combined effects of cisplatin (S phase arrest) and peanut testa extracts (G2/M phase arrest). In addition, pERK1/2, Ac-H3, Bcl-2 and proteins related to apoptosis, including Bax and caspases 3, 8, 9, exhibited enhanced expression in KKU-M214 cells. The combination treatments caused down-regulation of p53, whereas the expression of p21 was fairly constant when compared with cisplatin single drug treatment. Conclusions: Peanut testa extracts in combination with cisplatin synergistically reduce cell viability and induce apoptosis through stimulation of caspases 3, 8 and 9 in KKU-M214 cells.