Leelamine Exerts Antineoplastic Effects in Association with Modulating Mitogen‑Activated Protein Kinase Signaling Cascade

Abstract

Mitogen‑activated protein kinase (MAPK) pathway is a prominent signaling cascade that modulates cell proliferation, apoptosis, stress response, drug resistance, immune response, and cell motility. Activation of MAPK by various small molecules/natural compounds has been demonstrated to induce apoptosis in cancer cells. Herein, the effect of leelamine (LEE, a triterpene derived from bark of pine trees) on the activation of MAPK in hepatocellular carcinoma (HCC) and breast cancer (BC) cells was investigated. LEE induced potent cytotoxicity of HCC (HepG2 and HCCLM3) and BC (MDA-MB-231 and MCF7) cells over normal counterparts (MCF10A). LEE significantly enhanced the phosphorylation of p38 and JNK MAPKs in a dose-dependent fashion and it did not affect the phosphorylation of ERK in HCC and BC cells. The apoptosis-driving effect of LEE was further demonstrated by cleavage of procaspase-3/Bid and suppression of prosurvival proteins (Bcl-xL and XIAP). Furthermore, LEE also reduced the SDF1-induced-migration and -invasion of HCC and BC cells. Taken together, the data demonstrated that LEE promotes apoptosis and induces an anti-motility effect by activating p38 and JNK MAPKs in HCC and BC cells.

Data Availability Statement

The data used to support the findings of this study are available from the corresponding author upon request.

Disclosure Statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (NRF-2021R1I1A2060024). K.S.R. thanks to the University Grants Commission, New Delhi for providing the Basic Science Research faculty fellowship. K.S.R., and C.D.M., thanks DST-Promotion of University Research and Scientific (PURSE), Institution of Excellence, University of Mysore for providing laboratory facility. This project was supported by Researchers Supporting Project number (RSP-2022/383) King Saud University, Riyadh, Saudi Arabia.