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


Xia Xu
Hongbing Ma
Fujun Wang
Jiamiao Yan

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 downregulating the PI3K and MAPK pathways. Therefore, ITC may be beneficial for the treatment of cervical cancer.


Journal Identifiers


eISSN: 1596-9827
print ISSN: 1596-5996