Evaluation of new anti-neoplastic active ingredient in vitro

ABSTRACT

Drug development programs for identification of new anti-neoplastic agents involve extensive preclinical evaluation of vast numbers of chemicals for detection of anti-neoplastic activity. Cell culture systems have figured largely in the field of cancer chemotherapy, where the potential value of such systems for cytotoxicity and viability testing is now widely accepted. The aim of this study is to evaluate cytotoxicity and viability testing of new anti-neoplastic active ingredient compared to Methotrexate and Adriamycin anti-neoplastic active ingredients which are commonly used for cancer chemotherapy on HEPG[2], HEP[2] and VERO cell lines. Cytotoxicity, LD50, therapeutic dose, drug exposure, recovery period and stability bioassay are determined. Cytotoxicity bioassay of tested active ingredient on HEPG[2] cells showed punching of all monolayer cells with few regenerative cells after 48 hr and no regenerative cells after 72 hr while Methotrexate and Adriamycin showed 75% cytopathic effect on monolayer cells after 24 hr then cells begins to regenerate with few rate after 48-72 hr. Cytotoxicity bioassay of tested active ingredient on HEP[2] cells showed 25% cytopathic effect on monolayer cells then regenerated to reach complete monolayer after 72 hr compared to Methotrexate50% and Adriamycin 75% cytopathic effect on monolayer cells then reached to 75% of monolayer after 72 hr. Cytotoxicity of tested active ingredient onVero cells showed retraction of monolayer cells then retains its original pattern after 24 hr of exposure while Methotrexate and Adriamycin showed destruction of more 50% of monolayer cell population then reached to 75% of monolayer after 72 hr. In conclusion; cytopathological studies showed that the tested active ingredient has low cytotoxicity, more stable and more telorated compared to controls