Effect of Isocryptolepine Derivative on Ehrlich Ascites Carcinoma Cells in Mice via Regulation of Oxidative Stress and MAPK/JNK/mTOR Signaling Pathway

Ehrlich ascites carcinoma (EAC) is mammary adenocarcinoma model that is highly sensitive to chemotherapy. Major signaling cassettes of the mitogen-activated protein kinase (MAPK) signaling pathway include the c-Jun N-terminal kinase (JNK) and p38 pathways. They function in the number of cellular processes regulation, involving apoptosis, embryonic development, and proliferation. Isocryptolepine derivatives were examined for their anti-tumor properties because of their interaction with DNA base pairs and topoisomerase II. The present trail objectives to investigate the anticancer potency of the as prepared 6-aminopropyl amino isocryptolepine (6-APAI) on EAC in mice and its impact on JNK and p38 pathways via assessment of EAC cell viability, ascites volume, malondialdehyde, catalase activity and total antioxidant capacity, in addition, the mTOR and caspase-8 concentrations in EACs were determined, and JNK and p38 expression levels were also assessed. The findings indicated that 6-APAI has a cytotoxic effect on the viability of EAC cells and decreases the volume of ascites. Additionally, 6-APAI promotes oxidative stress and apoptosis. Moreover, it upregulates the expression of JNK and p38 in EACs indicated that the anticancer 6-APAI activity against EACs in mice is mediated by the JNK and p38 signaling pathways regulation.