Curcumol Induces Apoptosis in Tongue Squamous Cell Carcinoma Tca-8113 Cells by Activating p38 MAPK Mediated-mitochondrial Apoptotic Pathway

doi:10.13701/j.cnki.kqyxyj.2021.06.007

Abstract

Abstract: Objective: To investigate the effect of curcumol on apoptosis of human tongue squamous cell carcinoma Tca-8113 cells and its possible mechanism. Methods: Tca-8113 cells were treated with curcumol at different concentrations. The cell proliferation was detected by MTT assay, apoptosis rate and mitochondrial membrane potential change were evaluated by flow cytometry, and the expression levels of apoptosis-related proteins (Bax, Bcl-2, and Cleaved-caspase-3) and p38 MAPK signaling pathway related proteins (p-p38MAPK, p38MAPK, and Cyt C) in mitochondria and cytoplasm were detected by Western blot. Tca-8113 cells were treated with p38 MAPK inhibitor SB203580 combined with curcumol. The apoptosis rate and mitochondrial membrane potential change were detected by flow cytometry, and the expression levels of p38 MAPK signaling pathway related proteins (p-p38MAPK and p38MAPK) were detected by Western blot. Results: Curcumol inhibited the proliferation of Tca-8113 cells in a time and dose-dependent manner. Meanwhile, Curcumol significantly induced apoptosis, reduced mitochondrial membrane potential, and down-regulated the protein expression levels of Bcl-2 and Cyt C in mitochondria, and up-regulated the protein expression levels of Bax, Cleaved- caspase-3, p-p38 MAPK, and Cyt C in the cytoplasm. There was no significant change in the expression of P38 MAPK protein. However, SB203580 intervention inhibited the inducing effect of curcumol on Tca-8113 cell apoptosis, mitochondrial membrane potential change, and activation of p38 MAPK signaling pathway. Conclusion: Curcumol can promote the apoptosis of Tca-8113 cells, the mechanism may relate to the activation of p38 MAPK-mediated mitochondrial apoptotic pathway.

Key words: curcumol, tongue squamous cell carcinoma, apoptosis, mitochondrion, p38 MAPK signaling pathway

ZHANG Pei, ZHANG Lingnan, YANG Yong, MA Xiangrui. Curcumol Induces Apoptosis in Tongue Squamous Cell Carcinoma Tca-8113 Cells by Activating p38 MAPK Mediated-mitochondrial Apoptotic Pathway[J]. Journal of Oral Science Research, 2021, 37(6): 509-513.

References

[1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017 [J]. CA Cancer J Clin, 2017, 67(1):7-30.
[2] 王倩,侯大为.口腔鳞状细胞癌发病及转移机制研究进展[J].口腔医学研究,2018,34(11):1164-1167.
[3] Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015 [J]. CA Cancer J Clin, 2016, 66(2):115-132.
[4] Allemani C, Matsuda T, Di Carlo V, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries [J]. Lancet, 2018, 391(10125):1023-1075.
[5] 陈晓军,韦洁,苏华,等.莪术药理作用的研究新进展[J].药学研究,2018,37(11):664-668.
[6] Wei W, Rasul A, Sadiqa A, et al. Curcumol: from plant roots to cancer roots [J]. Int J Biol Sci, 2019, 15(8):1600-1609.
[7] 马春兰,张宝亮,张常虹.莪术醇对乳腺癌细胞增殖凋亡及JAK2/STAT3信号通路的影响[J].肿瘤学杂志,2020,26(7):616-620.
[8] 周微,韩景兰,李太红.莪术醇对非小细胞肺癌A549细胞侵袭、迁移及上皮间质转化的影响[J].中医学报,2019,34(8):1675-1680.
[9] 徐冰洁,何昌龙,赵静,等.线粒体功能紊乱与肿瘤[J].现代肿瘤医学,2018,26(5):772-776.
[10] 刘铮,张元霞,周萍,等.线粒体膜通透性增加引起凋亡机制的研究进展[J].哈尔滨医科大学学报, 2016, 50(1):90-93.
[11] Wang J, Huang F, Bai Z, et al. Curcumol inhibits growth and induces apoptosis of colorectal cancer LoVo cell line via IGF-1R and p38 MAPK pathway [J]. Int J Mol Sci, 2015, 16(8):19851-19867.
[12] Wang W, Wu J, Zhang Q, et al. Mitochondria-mediated apoptosis was induced by oleuropein in H1299 cells involving activation of p38 MAP kinase [J]. J Cell Biochem, 2019, 120(4):5480-5494.

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