JI017 Induces Cell Autophagy and Apoptosis via Elevated Levels of Reactive Oxygen Species in Human Lung Cancer Cells

Abstract

Lung cancer is one of the most common malignant tumors and a leading cause of cancer-related death in the worldwide. Various anticancer drugs, such as cisplatin and pemetrexed, have been developed for lung cancer treatment but due their drug resistance and side effects, novel treatments need to be developed. In this study, the efficacy of the natural drug JI017, which is known to have few side effects, was tested in lung cancer cells. JI017 inhibited A549, H460, and H1299 cell proliferation. JI017 induced apoptosis, regulated apoptotic molecules, and inhibited colony formation. Additionally, JI017 increased intracellular ROS generation. JI017 downregulated PI3K, AKT, and mTOR expression. JI017 increased the cytosolic accumulation of LC3. We found that JI017 promoted apoptosis through ROS-induced autophagy. Additionally, the xenograft tumor size was smaller in JI017-treated mice. We found that JI017 treatment increased MDA concentrations, decreased Ki-67 protein levels, and increased cleaved caspase-3 and LC3 levels in vivo. JI017 decreased cell proliferation and increased apoptosis by inducing autophagy signaling in H460 and H1299 lung cancer cells. Targeting JI017 and autophagy signaling could be useful in lung cancer treatment.

Inhibiting AGS Cancer Cell Proliferation through the Combined Application of Aucklandiae Radix and Hyperthermia: Investigating the Roles of Heat Shock Proteins and Reactive Oxygen Species

“…Both compounds are known for their broad-spectrum biological activities such as anti-inflammatory, anti-microbial, anti-ulcer, and anti-cancer features [51][52][53][54]. Notably, the mechanisms underlying their anti-cancer effects include inducing ROS and promoting apoptosis, which reflects our current findings [55][56][57]. Therefore, these two compounds may be the critical drivers of the synergistic effects observed in our study.…”

Revealing prognostic insights of programmed cell death (PCD)-associated genes in advanced non-small cell lung cancer

“…Ku et al discovered that JI017 can induce cell autophagy and apoptosis by enhancing ROS levels, reducing tumor size in lung cancer. This remarkable application of cell death regulation in cancer therapy exemplifies the potential of this approach in treating malignant tumors [ 14 ]. Furthermore, the induction of autophagy has been demonstrated to effectively overcome the resistance to third-generation EGFR-TKI treatment in patients with NSCLC [ 15 ].…”