Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Indole-thiophene conjugate inhibits proliferation of human cervical cancer cell lines through DNA damage

Xia Xu¹, Hongbing Ma², Fujun Wang¹, Jiamiao Yan¹

¹Department of Pharmacy; ²Department of Oncology, Ankang Hospital of Traditional Chinese Medicine, Ankang, Shaanxi 725000, China.

For correspondence:- Jiamiao Yan Email: markdaf@yahoo.com Tel:+869158183608

Accepted: 26 July 2019 Published: 28 August 2019

Citation: Xu X, Ma H, Wang F, Yan J. Indole-thiophene conjugate inhibits proliferation of human cervical cancer cell lines through DNA damage. Trop J Pharm Res 2019; 18(8):1705-1710 doi: 10.4314/tjpr.v18i8.20

© 2019 The authors.
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Abstract

Purpose: To investigate the inhibitory effect of indole-thiophene conjugate (ITC) against cervical cancer cells.

Methods: The effect of ITC on the proliferation of cervical cells was determined using 3 (4,5 dimethylthiazol 2 yl) 2,5 diphenyltetrazolium bromide (MTT) assay. The apoptosis-inducing effect of ITC was analysed with flow cytometry, while its effect on cell invasion was assessed using Transwell assay.

Results: ITC inhibited proliferation of HeLa and Caski cancer cell lines, but it had no cytotoxicity against HCvEpC normal epithelial cells. Exposure to ITC at a dose of 12 μmol/L reduced the viability of HeLa and Caski cells to 22.56 and 24.78 %, respectively (p < 0.05). ITC treatment of HeLa cells enhanced the proportion of apoptotic cells. Exposure to ITC at a dose of 12 μmol/L led to near-complete inhibition of the invasive potential of HeLa cells. Moreover, exposure of HeLa cells to ITC downregulated the protein expressions of MMP-2 and MMP-9 (p < 0.05). The expressions of Bcl-2, p-ERK1/2 and p-Akt were markedly decreased in HeLa cells by ITC exposure. In addition, ITC increased Bax expression, and decreased Bcl-2/Bax ratio (p < 0.05).

Conclusion: ICT inhibits the proliferation and invasion of cervical cancer cells, and induces their apoptosis. It exhibits these effects via the suppression of Akt and ERK phosphorylation, thereby down-regulating the PI3K and MAPK pathways. Therefore, ITC may be beneficial for the treatment of cervical cancer.

Keywords: Thiophenes, Hetero-aromatic compounds, Metastasis, Phosphorylation, Cervical cancer