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

Koraneekit,Amonrat; Limpaiboon,Temduang; Sangka,Arunnee; Boonsiri,Patcharee; Daduang,Sakda; Daduang,Jureerut

doi:10.3892/ol.2018.8256

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

Authors:
- Amonrat Koraneekit
- Temduang Limpaiboon
- Arunnee Sangka
- Patcharee Boonsiri
- Sakda Daduang
- Jureerut Daduang
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Affiliations: Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand, Department of Clinical Microbiology, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand, Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand, Division of Pharmacognosy and Toxicology, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
Published online on: March 13, 2018 https://doi.org/10.3892/ol.2018.8256
Pages: 7397-7402

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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 Chlorocebus sabaeus 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.

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