Anticancer Effects of New Indoloquinoline Analog against Ehrich Ascites Carcinoma Cells via Targeting Oxidative Stress, Apoptosis, and Proinflammatory Mediators

Cryptolepine, an indoloquinoline compound, is the primary alkaloid found in the roots of Cryptolepis sanguinolenta. It has numerous beneficial effects. The current study aims, for the first time, to assess the antitumor and immunomodulatory properties of novel indoloquinoline analog, IQBT, against Ehrlich ascites carcinoma cells (EACs), in comparison to doxorubicin drug. The anti-proliferative effect of IQBT on three human cancer cell lines MCF-7, Hep-G2, and HCT-116 was detected using MTT assay. Also, EACs were intraperitoneally inoculated in mice then EACs-bearing mice were treated with IQBT (100 mg/kg) every two days for two weeks (five doses). Effect of IQBT on EAC cell viability, antioxidant markers including reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) within the EAC cells was determined. Also, assessment of tumor cell apoptosis was done through flow cytometry. Furthermore, inflammatory mediators including cyclooxygenase-2 activity (COX-2), prostaglandin-E2 (PG-E2), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) were determined in liver tissue homogenates using mouse specific antibody ELISA kits. Results have revealed that IQBT exhibited anti-proliferative activity with IC50 values 2.44±0.8, 1.66±0.4, 12.3±1.8 µM for MCF-7, HepG-2, HCT116, respectively. Also, IQBT has potent antineoplastic activity, nearly comparable to that of doxorubicin, as evidenced by reductions in ascitic fluid volume, cell count, viability, and proliferation rate of inoculated tumor cells. Moreover, IQBT treatment led to an increased percentage of tumor inhibition, accompanied by the induction of apoptotic responses and oxidative stress within the EAC cells, compared with untreated mice. Furthermore, IQBT treatment demonstrated a remarkable effect on hepatic inflammatory mediators, particularly evident in the downregulation of COX-2 and PG-E2, exceeding the effects observed with doxorubicin treatment. In summary, our findings confirm that the new cryptolepine analog, IQBT, exhibited anticancer activity against EACs mediated by the induction of apoptosis, oxidative stress, and immune response modulation.