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Anticancer and cytotoxic effects of troxerutin on HeLa cell line: an in-vitro model of cervical cancer

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Abstract

Cervical cancer is one of the grave uterine tumors which leads to death in women worldwide. Troxerutin (TRX) as a bioflavonoid compound has many pharmacological effects such as anti-neoplastic, radioprotective, and anti-cancer. The present study was designed to examine the cytotoxic effect of TRX on human HeLa tumor cells. Human HeLa cells were cultured and treated with different doses of TRX (20–640 mg/ml) to evaluate the effective half-maximal inhibitory concentration (IC50) after 24 h. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test was used for cell proliferation assay. Also, the Bax, Bcl-2, cleaved caspase-3, and tumor necrosis factor-α (TNF-α) protein expression levels were detected with immunoblotting analysis. The malondialdehyde (MDA) concentration, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity levels were measured via their commercial kits. Data were analyzed using one-way ANOVA. The result showed that TRX at 320 mg/ml concentration (IC50) has a growth inhibitory effect against HeLa cells at 24 h treatment (P ˂ 0.01). Moreover, it increased the MDA concentration and also decreased the GPx and SOD activity levels at 320 mg/ml concentration versus control (P < 0.001). Also, TRX significantly up-regulated the Bax, cleaved caspase-3 and TNF-α proteins expression levels (P  <  0.01) and down-regulated the Bcl-2 protein expression in HeLa tumor cells at 320 mg/ml concentration compared to control (P < 0.05). Our study showed that 24 h of treatment with TRX (320 mg/ml) has apoptotic and growth inhibitory effects against HeLa cells. It can induce inflammation (at least via up-regulating the TNF-α protein expression) and oxidative stress in human HeLa cells.

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Acknowledgements

This study was supported by Rafsanjan University of Medical Sciences (Grant No. 98267).

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Authors and Affiliations

  1. Physiology-Pharmacology Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

    Jalal Hassanshahi & Ayat Kaeidi

  2. Department of Physiology and Pharmacology, Faculty of Medicine, Rafsanjan University of Medical Sciences, Khalije Fars Blvd., Pistachio Co. Street, Rafsanjan, P.O. Box: 77175-835, 7719617996, Iran

    Jalal Hassanshahi & Ayat Kaeidi

  3. Department of Clinical Biochemistry, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

    Afsaneh Mirzahosseini-pourranjbar

  4. Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran

    Zahra Hajializadeh

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  1. Jalal Hassanshahi
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  2. Afsaneh Mirzahosseini-pourranjbar
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  3. Zahra Hajializadeh
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  4. Ayat Kaeidi
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Contributions

Conceived and designed the experiments: AK, JH, ZH. Performed the experiments: AK, JH, AM and ZH. Analyzed the data: AK and ZH. Contributed reagents/materials/analysis tools: AK and JH. Wrote the paper: JH, AM, AK and ZH.

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Correspondence to Ayat Kaeidi.

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Hassanshahi, J., Mirzahosseini-pourranjbar, A., Hajializadeh, Z. et al. Anticancer and cytotoxic effects of troxerutin on HeLa cell line: an in-vitro model of cervical cancer. Mol Biol Rep 47, 6135–6142 (2020). https://doi.org/10.1007/s11033-020-05694-y

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