Ethyl acetate extract of Elephantopus mollis Kunth. induced apoptosis, senescence, and inhibited metastasis-associated traits of human lung cancer cells.

Elephantopus mollis Kunth. (EM) is an attractive candidate for cancer treatment research due to its long history of use in traditional cancer remedies. As lung cancer is the most widespread and among the most lethal carcinomas, we assessed the toxicity and anti-metastatic ability of EM extracts on the lung cancer NCI-H1299 cells. The cytotoxicity of EM extracts was evaluated via the MTT assay. Phytopolyphenol constituents of the potent extract were evaluated by HPLC. The underlying mechanisms of this toxicity were scrutinized by cellular and nuclear morphologies, cleaved caspase-3/8/9 staining, senescence-associated beta-galactosidase activity, and gene expression analysis. The scratch, invasion, adhesion assays, and RT-qPCR were employed for the anti-metastasis study. The ethyl acetate fraction (EMEA) was the most potent extract against NCI-H1299 cells, with a low IC50 and an impressive selective effect. Most attractively, this is the very first study showing that EMEA induced both apoptosis and senescence in a cancer cell line. The underlying mechanisms involved the extrinsic apoptotic pathway, DNA damage, p21-dependent cell-cycle arrest, and oxidative stress response. EMEA could also strongly inhibit the migration, invasion, and collagen I adhesion abilities of NCI-H1299 cells. This might stem from the reduction of two crucial metastatic MMP2 and VIM genes. As interesting as the cytotoxic findings, this is among the surprisingly sparse studies on the anti-metastasis activity of EM extracts and compounds. Our research contributed considerably to the knowledge of anticancer properties of EM and cemented its role as a promising source for novel cancer treatment therapies.