beta-elemene suppresses tumor metabolism and stem cell-like properties of non-small cell lung cancer cells by regulating PI3K/AKT/mTOR signaling

Multi-drug resistance remains a critical issue in cancer treatment that hinders the effective use of chemotherapeutic drugs. The active components of traditional Chinese medicine have been applied as adjuvants to accentuate the anticancer properties of conventional drugs such as cisplatin. However, their application requires further validation and optimization. This study explored the anticancer activity of beta-elemene, a natural component of traditional Chinese medical formulations. The effect of beta-elemene on the anticancer properties of cisplatin was evaluated in A549 and NCI-H1650 lung cancer cells. Cell apoptosis, stem-like properties, glucose metabolism, multi-drug resistance, and PI3K/AKT/mTOR activation were assessed via flow cytometry, tumorsphere formation, and western blotting. The target genes of beta-elemene were predicted using bioinformatics tools and validated in both cell lines. A xenograft model of lung cancer was established in nude mice to evaluate the combined effects of beta-elemene and cisplatin in vivo. We found that beta-elemene acted synergistically with cisplatin against non-small cell lung cancer cells by promoting apoptosis and impairing glucose metabolism, multi-drug resistance, and stemness maintenance. These effects were mediated by the inhibition of PI3K/AKT/mTOR activation. Bioinformatics analysis revealed that RB1 and TP53 are common target genes associated with lung cancer and beta-elemene. The anti-tumorigenic properties of beta-elemene were confirmed in vivo, wherein beta-elemene, along with cisplatin, significantly suppressed tumor growth in a mouse xenograft model of non-small cell lung cancer. As such, beta-elemene acted as an inhibitor of PI3K/AKT/mTOR signaling and enhanced the anticancer effect of cisplatin by targeting tumor metabolism, chemoresistance, and stem-like behavior. Thus, beta-elemene is an effective anticancer adjuvant agent with potential clinical applications.