RESUMO
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.
RESUMO
BACKGROUND: Most northeast Thai vegetables may play roles in human health by acting as antioxidant and anticancer agents. Recent study showed that Cratoxylum formosum subsp. pruniflorum (Kurz.) Gogel. (Teawdang) could inhibit growth of liver cancer cell lines. Cervical cancer, which has human papilloma virus as its main cause, is found at high incidence in Thailand. Due to increasing drug resistance, searches for potential anticancer compounds from natural source are required. Therefore, our purpose was to evaluate the cytotoxicity of Teawdang extracts in cervical cancer cell lines. MATERIALS AND METHODS: Teawdang edible parts, purchased from Khon Kaen market during July-October 2013 was extracted with organic solvent. Phenolic profiles of crude hexane (CHE), ethyl acetate (CEE), methanol (CME) and water (CWE) extracts were performed by high performance liquid chromatographic (HPLC) techniques. Their cytotoxic effects on cervical cancer cells were investigated with HPV-non infected (C-33A) and HPV-infected (HeLa and SiHa) cell lines. RESULTS: HPLC profiles showed that all crude extracts contained caffeine, ferulic acid and resveratrol. CME and CEE had high contents of gallic acid and quercetin. Catechin was found only in CWE. Cytotoxicity test showed that CEE had the lowest IC50 on HeLa (143.18±13.35 µg/mL) and SiHa cells (106.45±15.73 µg/mL). C-33A cells were inhibited by CWE (IC50 = 130.95±3.83 µg/mL). CONCLUSIONS: There were several phenolic compounds in Teawdang extracts which may have cytotoxic effects on cervical cancer cell lines. Investigation of these bioactive compounds as new sources of anticancer agents is recommended.