Abstract 707: Mahanine, a carbazole alkaloid attenuates lung cancer progression

Abstract

Abstract Lung cancer continues to be a major cause of cancer mortality. Emerging evidence suggests that cancer likely involves multiple mutations. Therefore, compounds targeting multiple signal transduction pathways would be ideal for the prevention and treatment of cancer. Mahanine, a carbazole alkaloid isolated from an Indian folklore medicinal plant Murraya koenigii (known as Curry Patta), widely consumed in traditional dishes, have been shown to possess anticancer activities and confound many oncogenic signaling events in breast, colon, and prostate cancers. In the current study, we determined the anticancer potential of mahanine against drug-sensitive and drug-resistant lung cancer cells and postulate the possible mechanism of action. Mahanine was isolated from the dried leaves of Murraya koenigii by hydro alcoholic extraction and fractionation with ethyl acetate, followed by preparative UPLC to isolate pure (>95%) compound and its identity was confirmed by LC-MS/MS and NMR spectroscopy. Antiproliferative activity of mahanine was determined against drug- sensitive (A549 and H1299) and taxol-resistant (A549-TR) human lung cancer cells. Mahanine showed a dose- and time-dependent inhibition of both drug-sensitive and drug-resistant lung cancer cell growth. Interestingly, the IC50 values of mahanine were essentially the same for drug sensitive (A549) (12.5 µM) and drug- resistant (12.5 µM) lung cancer cells; the IC50 value was somewhat lower (10 µM) against highly metastatic H1299 lung cancer cells. Mahanine attenuated the colony formation and reduced the wound healing of lung cancer cells. Mechanistically, mahanine dose dependently impeded the oncogenic markers such as KRAS, MET, AKT, mTOR and cMYC. Together, mahanine demonstrate ability to inhibit both drug- sensitive and drug-resistant lung cancer cells and modulate distinct oncogenic molecular targets providing potential to be developed for the treatment of drug-resistant and metastatic NSCLC (Supported from Duggan Endowment funds). Keywords: Mahanine, Lung cancer, Oncogenes, Plant therapeutics. Citation Format: Raghuram Kandimalla, Farrukh Aqil, Disha N. Moholkar, Suman K. Samanta, Ramesh C. Gupta. Mahanine, a carbazole alkaloid attenuates lung cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 707.