PPARα plays an important role in the migration activity, and the expression of CYP2S1 and CYP1B1 in chrysin-treated HCT116 cells
Tóm tắt
This study aimed to examine the metabolising effect of chrysin by investigating the mRNA expression levels of PPARα and its related cellular mechanisms in HCT116 cells. The mRNA expression of PPARα was significantly induced in HCT116 cells following treatment with chrysin for 36 h, but the mRNA expression of PPARα was inhibited, when the cells were treated with a combination of chrysin and MK886 (PPARα inhibitor). This phenomenon proved that the incorporation of MK886 lowers the expression levels of PPARα, thus enabling us to study the function of PPARα. The cell population of the G0/G1 phase significantly increased in chrysin-treated cells, which was accompanied by a decrease in the percentage of S phase cell population after 12 h of treatment. However, treatments of HCT116 cells with chrysin only or a combination of chrysin and MK886 did not show the opposite situation in the G0/G1 and S phase cell populations, indicating that the expression of PPARα may not be associated with the cell cycle in the treated cells. The migration rate in chrysin-treated HCT116 cells was reduced significantly after 24 and 36 h of treatments. However, the activity was revived, when the expression of PPARα was inhibited, indicating that the migration activity of chrysin-treated cells is likely correlated with the expression of PPARα. Comparison of the CYP2S1 and CYP1B1 mRNA expression in chrysin only treated, and a combination of chrysin and MK886-treated HCT116 cells for 24 and 36 h showed a significant difference in the expression levels, indicating that PPARα inhibitor could also modify the expression of CYP2S1 and CYP1B1. The study indicates that PPARα may play an essential role in regulating the migration activity, and the expression of CYP2S1 and CYP1B1 in chrysin-treated colorectal cancer cells.
Tài liệu tham khảo
Al-Ani I, Zimmermann S, Reichling J, Wink M (2018) Antimicrobial activities of European propolis collected from various geographic origins alone and in combination with antibiotics. Medicines (Basel) 5(1):2. https://doi.org/10.3390/medicines5010002
Androutsopoulos VP, Spyrou I, Ploumidis A, Papalampros AE, Kyriakakis M, Delakas D, Spandidos DA, Tsatsakis AM (2013) Expression profile of CYP1A1 and CYP1B1 enzymes in colon and bladder tumors. PLoS ONE 8(12):e82487. https://doi.org/10.1371/journal.pone.0082487
Araújo JR, Gonçalves P, Martel F (2011) Chemopreventive effect of dietary polyphenols in colorectal cancer cell lines. Nutr Res 31(2):77–87. https://doi.org/10.1016/j.nutres.2011.01.006
Bernardo A, Minghetti L (2006) PPAR-gamma agonists as regulators of microglial activation and brain inflammation. Curr Pharm Des 12(1):93–109. https://doi.org/10.2174/138161206780574579
Brown CM, Reisfeld B, Mayeno AN (2008) Cytochromes P450: a structure-based summary of biotransformations using representative substrates. Drug Metab Rev 40(1):1–100. https://doi.org/10.1080/03602530802309742
Chen HY, Jiang YW, Kuo CL, Wa TD, Chou YC, Chang YS, Chung JG (2019) Chrysin inhibit human melanoma A375.S2 cell migration and invasion via affecting MAPK signaling and NF-κB signaling pathway in vitro. Environ Toxicol 34(4):434–442. https://doi.org/10.1002/tox.22697
Chinetti G, Fruchart JC, Staels B (2000) Peroxisome proliferator-activated receptors (PPARs): nuclear receptors at the crossroads between lipid metabolism and inflammation. Inflamm Res 49(10):497–505. https://doi.org/10.1007/s000110050622
Chun YJ, Kim D (2016) Cancer activation and polymorphisms of human cytochrome P450 1B1. Toxicol Res 32(2):89–93. https://doi.org/10.5487/TR.2016.32.2.089
Contreras AV, Torres N, Tovar AR (2013) PPAR-α as a key nutritional and environmental sensor for metabolic adaptation. Adv Nutr 4(4):439–452. https://doi.org/10.3945/an.113.003798
Danielson PB (2002) The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans. Curr Drug Metab 3(6):561–597. https://doi.org/10.2174/1389200023337054
Gillet JP, Gottesman MM (2010) Mechanisms of multidrug resistance in cancer. Methods Mol Biol 596:47–76. https://doi.org/10.1007/978-1-60761-416-6_4
Gonçalves P, Araújo JR, Pinho MJ, Martel F (2011) In vitro studies on the inhibition of colon cancer by butyrate and polyphenolic compounds. Nutr Cancer 63(2):282–294. https://doi.org/10.1080/01635581.2011.523166
Grabacka M, Plonka PM, Urbanska K, Reiss K (2006) Peroxisome proliferator-activated receptor α activation decreases metastatic potential of melanoma cells in vitro via down-regulation of Akt. Clin Cancer Res 12(10):3028–3036. https://doi.org/10.1158/1078-0432.CCR-05-2556
Grau R, Punzón C, Fresno M, Iñiguez MA (2006) Peroxisome-proliferator-activated receptor α agonists inhibit cyclooxygenase-2 and vascular endothelial growth factor transcriptional activation in human colorectal carcinoma cells via inhibition of activator protein-1. Biochem J 395(1):81–88. https://doi.org/10.1042/BJ20050964
Jang CH, Moon N, Oh J, Kim J-S (2019) Luteolin shifts oxaliplatin-induced cell cycle arrest at G0/G1 to apoptosis in HCT116 human colorectal carcinoma cells. Nutrients 11(4):770. https://doi.org/10.3390/nu11040770
Khoo BY, Chua SL, Balaram P (2010) Apoptotic effects of chrysin in human cancer cell lines. Int J Mol Sci 11(5):2188–2199. https://doi.org/10.3390/ijms11052188
Kostadinova R, Wahli W, Michalik L (2005) PPARs in diseases: control mechanisms of inflammation. Curr Med Chem 12(25):2995–3009. https://doi.org/10.2174/092986705774462905
Lalou C, Basak A, Mishra P, Mohanta BC, Banik R, Dinda B, Khatib AM (2013) Inhibition of tumor cells proliferation and migration by the flavonoid furin inhibitor isolated from Oroxylum indicum. Curr Med Chem 20(4):583–591. https://doi.org/10.2174/0929867311320040010
Li X, Huang Q, Ong CN, Yang XF, Shen HM (2010) Chrysin sensitizes tumor necrosis factor-alpha-induced apoptosis in human tumor cells via suppression of nuclear factor-kappaB. Cancer Lett 293(1):109–116. https://doi.org/10.1016/j.canlet.2010.01.002
Lin YM, Chen CI, Hsiang YP, Hsu YC, Cheng KC, Chien PH, Pan HL, Lu CC, Chen YJ (2018) Chrysin attenuates cell viability of human colorectal cancer cells through autophagy induction unlike 5-fluorouracil/oxaliplatin. Int J Mol Sci 19(6):1763. https://doi.org/10.3390/ijms19061763
Miyamoto S, Kohno H, Suzuki R, Sugie S, Murakami A, Ohigashi H, Tanaka T (2006) Preventive effects of chrysin on the development of azoxymethane-induced colonic aberrant crypt foci in rats. Oncol Rep 15(5):1169–1173
Morinishi T, Tokuhara Y, Ohsaki H, Ibuki E, Kadota K, Hirakawa E (2019) Activation and expression of peroxisome proliferator-activated receptor alpha are associated with tumorigenesis in colorectal carcinoma. PPAR Res 2019:7486727. https://doi.org/10.1155/2019/7486727
Mueller O, Hahnenberger K, Dittmann M, Yee H, Dubrow R, Nagle R, Ilsley D (2000) A microfluidic system for high-speed reproducible DNA sizing and quantitation. Electrophoresis 21(1):128–134. https://doi.org/10.1002/(SICI)1522-2683(20000101)21:1%3c128:AID-ELPS128%3e3.0.CO;2-M
Mukherjee AK, Basu S, Sarkar N, Ghosh AC (2001) Advances in cancer therapy with plant based natural products. Curr Med Chem 8(12):1467–1486. https://doi.org/10.2174/0929867013372094
Nebert DW, Russell DW (2002) Clinical importance of the cytochromes P450. Lancet 360(9340):1155–1162. https://doi.org/10.1016/S0140-6736(02)11203-7
Nuchtavorn N, Smejkal P, Breadmore MC, Guijt RM, Doble P, Bek F, Foret F, Suntornsuk L, Macka M (2013) Exploring chip-capillary electrophoresis-laser-induced fluorescence field-deployable platform flexibility: Separations of fluorescent dyes by chip-based non-aqueous capillary electrophoresis. J Chromatogr A 1286:216–221. https://doi.org/10.1016/j.chroma.2013.02.060
Ohe Y (2002) Treatment-related death from chemotherapy and thoracic radiotherapy for advanced cancer. Panminerva Med 44(3):205–212
Rehman MU, Ali N, Rashid S, Jain T, Nafees S, Tahir M, Khan AQ, Lateef A, Khan R, Hamiza OO, Kazim S, Qamar W, Sultana S (2014) Alleviation of hepatic injury by chrysin in cisplatin administered rats: probable role of oxidative and inflammatory markers. Pharmacol Rep 66(6):1050–1059. https://doi.org/10.1016/j.pharep.2014.06.004
Ronnekleiv-Kelly SM, Nukaya M, Díaz-Díaz CJ, Megna BW, Carney PR, Geiger PG, Kennedy GD (2016) Aryl hydrocarbon receptor-dependent apoptotic cell death induced by the flavonoid chrysin in human colorectal cancer cells. Cancer Lett 370(1):91–99. https://doi.org/10.1016/j.canlet.2015.10.014
Shao JJ, Zhang AP, Qin W, Zheng L, Zhu YF, Chen X (2012) AMP-activated protein kinase (AMPK) activation is involved in chrysin-induced growth inhibition and apoptosis in cultured A549 lung cancer cells. Biochem Biophys Res Commun 423(3):448–453. https://doi.org/10.1016/j.bbrc.2012.05.123
Shimada T, Fujii-Kuriyama Y (2004) Metabolic activation of polycyclic aromatic hydrocarbons to carcinogens by cytochromes P450 1A1 and 1B1. Cancer Sci 95(1):1–6. https://doi.org/10.1111/j.1349-7006.2004.tb03162.x
Siess M-H, Le Bon A-M, Canivenc-Lavier M-C, Amiot M-J, Sabatier S, Aubert SY, Suschetet M (1996) Flavonoids of Honey and propolis: characterization and effects on hepatic drug-metabolizing enzymes and benzo[a]pyrene−DNA binding in rats. J Agric Food Chem 44(8):2297–2301. https://doi.org/10.1021/jf9504733
Sithisarn P, Rojsanga P, Sithisarn P (2019) Inhibitory effects on clinical isolated bacteria and simultaneous HPLC quantitative analysis of flavone contents in extracts from Oroxylum indicum. Molecules 24(10):1937. https://doi.org/10.3390/molecules24101937
Strakova N, Ehrmann J, Bartos J, Malikova J, Dolezel J, Kolar Z (2005) Peroxisome proliferator-activated receptors (PPAR) agonists affect cell viability, apoptosis and expression of cell cycle related proteins in cell lines of glial brain tumors. Neoplasma 52(2):126–136
Thomas M, Burk O, Klumpp B, Kandel BA, Damm G, Weiss TS, Klein K, Schwab M, Zanger UM (2013) Direct transcriptional regulation of human hepatic cytochrome P450 3A4 (CYP3A4) by peroxisome proliferator-activated receptor alpha (PPARα). Mol Pharmacol 83(3):709–718. https://doi.org/10.1124/mol.112.082503
Thomas M, Winter S, Klumpp B, Turpeinen M, Klein K, Schwab M, Zanger UM (2015) Peroxisome proliferator-activated receptor alpha, PPARα, directly regulates transcription of cytochrome P450 CYP2C8. Front Pharmacol 6:261. https://doi.org/10.3389/fphar.2015.00261
Wang J, Wang H, Sun K, Wang X, Pan H, Zhu J, Ji X, Li X (2018) Chrysin suppresses proliferation, migration, and invasion in glioblastoma cell lines via mediating the ERK/Nrf2 signaling pathway. Drug Des Devel Ther 12:721–733. https://doi.org/10.2147/DDDT.S160020
Williams CA, Harborne JB, Newman M, Greenham J, Eagles J (1997) Chrysin and other leaf exudate flavonoids in the genus Pelargonium. Phytochemistry 46(8):1349–1353. https://doi.org/10.1016/s0031-9422(97)00514-1
Xu D, Jin J, Yu H, Zhao Z, Ma D, Zhang C, Jiang H (2017) Chrysin inhibited tumor glycolysis and induced apoptosis in hepatocellular carcinoma by targeting hexokinase-2. J Exp Clin Cancer Res 36:44. https://doi.org/10.1186/s13046-017-0514-4
Yang C, Li C, Li M, Tong X, Hu X, Yang X, Yan X, He L, Wan C (2015) CYP2S1 depletion enhances colorectal cell proliferation is associated with PGE2-mediated activation of β-catenin signaling. Exp Cell Res 331(2):377–386. https://doi.org/10.1016/j.yexcr.2014.12.008
Yang C, Zhou Q, Li M, Tong X, Sun J, Qing Y, Sun L, Yang X, Hu X, Jiang J, Yan X, He L, Wan C (2016) Upregulation of CYP2S1 by oxaliplatin is associated with p53 status in colorectal cancer cell lines. Sci Rep 6:33078. https://doi.org/10.1038/srep33078