Effects of Irinotecan (CPT-11), Ellagic Acid and Combination of both on HeLa Cells in 2D and 3D Culture

BACKGROUND/AIMS: Investigation of new potential treatments is important today to increase the power of cervical carcinoma treatment. Although chemotherapeutic drugs are widely used for clinical tumor treatment, their severe toxicity limits their therapeutic efficacy. Irinotecan (CPT-11) is an agent with therapeutic activity against various cancers including cervical cancer. Ellagic acid (EA) is a phenolic natural substance that can be found in various fruits and has chemopreventive and chemotherapeutic effects. In this work, we looked into EA as an alternative agent to improve the therapeutic effect of CPT-11 in vitro. MATERIALS AND METHODS: The effects of the two agents and their combination on 2 and 3D HeLa cultures at different time periods were evaluated by real-time-polymerase chain reaction and intraclass correlation coefficient analyses. In cultures, MMP-2 and -9 were used to determine the basis of cancer cell metastasis, HIF1 & alpha; and TGF-131 were used to evaluate the mechanism of angiogenesis and epithelialmesenchymal change, and Bax and Bcl-2 were used to evaluate the apoptotic mechanism. RESULTS: In comparison to the DMSO (Dimethyl Sulfoxide) group, HeLa cells treated with EA and its combination showed considerable suppression of MMPs, TGF-131, and HIF1 & alpha;. In addition, the increase in proapoptotic Bax level with treatment and the suppression of antiapoptotic Bcl-2 expression were revealed as another important finding of EA and combined treatment. CONCLUSION: We propose that EA would be a good candidate for additional preclinical studies for the management of human cervical cancer.