The molecular mechanism of shikonin in promoting caspase-9 activation and inducing apoptosis in colorectal cancer cells

doi:10.3877/cmj.j.issn.2095-1221.2020.01.003

Abstract

Abstract:

Objective

To investigate the anti-tumor effect and mechanism of shikonin on colorectal cancer cell LoVo.

Methods

The colorectal cancer cell LoVo was treated with different concentration gradients (0, 2, 4, 6 μmol/L) for 24 hours. Besides, the other colorectal cancer cell LoVo was treated with 4μmol/L of shikonin according to different time gradients (0, 12, 24, 48 h) . The apoptosis rate was determined by flow cytometry combined with Annexin V-FITC/PI double staining. The expression and cleavage of caspase-9 protein were detected by Western blot. ANOVA and LSD-t tests were conducted to compare the average values between the control and experimental groups.

Results

Compared with the colorectal cancer cell LoVo treated with 0 μmol/L for 24 hours, the apoptosis rate of colorectal cancer cell LoVo treated with 2, 4, 6 μmol/L for 24 hours were increased [ (6.94±1.02) ﹪ vs (10.61±1.12) ﹪, (15.55±1.35) ﹪ and (36.51±1.46) ﹪]. Compared with the colorectal cancer cell LoVo treated with 4 μmol/L for 0 hours, the apoptosis rate of colorectal cancer cell LoVo treated with 4 μmol/L for 12 hours, 24 hours and 48 hours were increased [ (1.33±0.59) ﹪vs (19.23±1.24) ﹪, (22.24±1.41) ﹪ and (28.41±1.52) ﹪], differences were statistically significant (P< 0.001) . In the mean time, caspase-9 protein was up-regulated and activated when shikonin dose was≥2 μmol/L and treatment time was≥12 h, while caspase inhibitor (Z-LEHD-FMK) pretreatment could reduced the apoptosis rate significantly (P< 0.001) , by approximately 38.7﹪ (P< 0.05) .

Conclusion

Shikonin could induce apoptosis of colorectal cancer cells by regulating the expression of caspase-9 protein and its cleavage activity.

Key words: Colon cancer, Apoptosis, Caspase-9, Shikonin

Ding Zhang, Jianli Xu, Ming Li, Yanhua Sun, Lu Dong, Xubin Cao, Xiaojing Meng. The molecular mechanism of shikonin in promoting caspase-9 activation and inducing apoptosis in colorectal cancer cells[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2020, 10(01): 13-19.

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Figures/Tables 8

References 21

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