Combinatorial Mitochondria-Targeted Drug Therapy as a Novel Option for Lung Cancer Prevention

Previous studies have reported on the ability of honokiol—a natural compound present in magnolia bark extracts—and lonidamine—which has been used with standard-of-care chemotherapeutics in clinical trials for cancers—to inhibit complex I- and complex II-induced respiration and proliferation in cancer cells. A new study, titled “Chemoprevention of Lung Cancer with a Combination of Mitochondria-Targeted Compounds” and published in Cancers, investigated the efficacy of a combined treatment of mitochondria-targeted honokiol and mitochondria-targeted lonidamine for lung cancer prevention.

The study found, using the single-cell RNA sequencing technique, that combined treatment with mitochondria-targeted honokiol and mitochondria-targeted lonidamine significantly inhibited two oncogenic pathways—STAT3 signaling and AKT/mTOR/p70S6K signaling. Dual inhibition of these pathways may contribute to the greater efficacy of the combined drug treatment, making their combination a novel chemopreventive approach for mitigating lung cancer development, progression, and metastasis.

This article is the result of an international collaboration among the authors: Balaraman Kalyanaraman, PhD, chair and professor of biophysics and the Harry R. & Angeline E. Quadracci Professor in Parkinson’s Research at MCW; Qi Zhang, PhD, Donghai Xiong, PhD, Jing Pan, PhD, Yian Wang, PhD, and Ming You, MD, PhD, at Houston Methodist Research Institute in Texas; and Micael Hardy, PhD, at Aix-Marseille Université in France.