Synergistic effects of cisplatin-caffeic acid induces apoptosis in human cervical cancer cells via the mitochondrial pathways

Abstract

Cervical cancer (CxCa) is a major health problem globally and is associated with the presence of human papillomavirus infection. Cisplatin (CDDP) is a platinum-based chemotherapeutic agent. Owing to its side effects and drug-resistance, novel anticancer agents with lower toxicity, including caffeic acid (CFC), are of interest. However, the effects of CDDP and CFC in combination are, to the best of our knowledge, uninvestigated. The present study investigated the effectiveness of CDDP and CFC in combination and its mechanism of action on four human cervical cancer cell lines, which were compared with the normal kidney Vero cell line. Cell viability was evaluated using a sulforhodamine B assay. Caspase-Glo assay kits, measuring the activity of caspases-3, -7, -8 and -9, were used to detect caspase activation in HeLa and CaSki cell lines in response to CDDP and CFC in combination. The results revealed that CDDP and CFC alone reduced the proliferation of HeLa, CaSki, SiHa and C33A cell lines. Treatment with CFC exhibited no significant cytotoxicity towards Vero cells. In addition, CDDP-CFC significantly inhibited cell growth of HeLa and CaSki cell lines. In HeLa and CaSki cell lines, a combination index<1 for CDDP and CFC indicated the synergistic growth inhibition; the combination of the two also significantly increased expression of caspase-3, -7 and -9. In conclusion, CFC may be a candidate anticancer agent that, when use in combination, may increase the therapeutic efficacy of CDDP.

Pentoxifylline Sensitizes Cisplatin-Resistant Human Cervical Cancer Cells to Cisplatin Treatment: Involvement of Mitochondrial and NF-Kappa B Pathways

“…Likewise, several studies have shown that chemoresistance is intimately linked to cell type and to the inherent self-response capacity of the cells in terms of prolonged exposure to the drug. These findings are consistent with those of a previous study where was reported that HeLa cells are more sensitive to Cisplatin than are CaSki cells and SiHa cells (20).…”

Therapeutic Potential of Plant Phenolic Acids in the Treatment of Cancer

“…GeA as well as GA attenuated side effects of doxorubicin [17] and paclitaxel [43]. Additionally, GA was found to sensitize paclitaxel resistant cancer cells [44] and CA increased therapeutic potential of cisplatin [67]. Moreover, we emphasize important role of phenolics as epigenetic regulators.…”

Non-Steroidal Anti-Inflammatory Drugs Increase Cisplatin, Paclitaxel, and Doxorubicin Efficacy against Human Cervix Cancer Cells

“…In order to demonstrate whether a combination of celecoxib with canonical drugs also affects other cervix cancer lines, drugs were tested on the cellular growth and OxPhos flux of SiHa cells ( Figure S6 ). The synergistic concentrations of celecoxib/paclitaxel or celecoxib/cisplatin used in bidimensional ( Table 2 ) and tridimensional HeLa cell cultures, in both preventive and curative ( Table 3 ) protocols, were very toxic for SiHa bidimensional and MCTS cell cultures (cellular viability decreased >70%), indicating that this cancer cell line is much less drug-resistant than HeLa cells [ 52 , 53 ]. Therefore, the IC 50 proliferation values for each assayed drug were determined in SiHa bidimensional and MCTS cells.…”