Comparative study for toxic Effects of Camptothecin in Cancer and Normal Cells

The goal of oncologists of chemotherapy is to minimize damage to normal cellsand to enhance the toxic effect on cancer cells. In terms of chemotherapy, adrug is useful when there is significant distance between its necrotic andapoptosis effect. Therefore, the present study was to understand the distancebetween necrotic effect and apoptotic nature of Camptothecin (CPT) asanticancer drug in human epithelial pharyngeal carcinoma tissue cells (HEp-2)and MRC-5 normal cells. Cytotoxicity, cytosolic enzyme lactate dehydrogenase(LDH) and DNA fragmentation and caspase-8 were assessed in HEp-2 cells andMRC-5 normal cells under unexposed and CPT exposed conditions. The MTTassay showed that CPT inhibited the proliferation of HEp-2 cells in a dosedependentmanner with an IC50 of 0.05±0.022 μg/ml. However, the inhibitioneffect of CPT on MRC-5 cells was about 45% at concentration 6×10-1μg/ml.On the other hand significant (P<0.05) increase in LDH released activity wasobserved in MRC-5 cultured cells when exposed to concentrations 2×10-2μg/mland above. The activity of caspase-8 in HEp-2 cells at IC50 concentration was1.8 folds greater than unexposed cells. Caspase-8 activity on MRC-5 cells wasnot significantly different as compared to unexposed MRC-5 cells. The DNAladder formation also confirmed the results obtained by MTT and LDH assay.Based on the results obtained in this study, there is no significant distancebetween necrotic effect and apoptotic nature of CPT in both cancer and normalcells. Hence using this model for newly developed anticancer drugs at primarysteps can be considered as a model for the toxicity evaluation of the compounds.

کلیدواژه ها:

Necrosis ، Apoptosis ، Camptothecin ، Cancer cells ، Normal cells