Abstract
Overexpressed survivin is associated with worse survival of several types of human tumors. In this study, the antitumor activity of shikonin in non-small-cell lung cancer (NSCLC) by regulating survivin pathway was investigated. Results showed that shikonin inhibited the NSCLC H1299 cell proliferation in a dose-dependent manner. Moreover, shikonin fits well with survivin by molecular docking. Shikonin also inhibited the mRNA expression and protein level of survivin in H1299 cells. Shikonin arrested H1299 cell cycle at the G0/G1 phase by regulating CDK/cyclin family members. In addition, shikonin regulated the expression of X-linked inhibitor of apoptosis- (XIAP-) mediated caspases 3 and 9, thus leading to the damage of mitochondrial membrane potential and induction of H1299 cell apoptosis. Overall, shikonin inhibited H1299 cell growth by inducing apoptosis and blocking the cell cycle. The underlying mechanism involves targeting survivin, which subsequently regulates the protein expression of XIAP/caspase 3/9, CDK2/4, and cyclin E/D1. Thus, shikonin, a survivin inhibitor, is a promising therapeutic strategy in NSCLC treatment.
Highlights
Lung cancer is one of the deadliest cancers worldwide
Results showed that shikonin inhibited both H1299 and H460 cell proliferation and that H1299 cells were slightly more sensitive to shikonin than H460 cells (Figure 1(b))
We demonstrated that shikonin inhibited H1299 cell proliferation by blocking the cell cycle and inducing cell apoptosis, which were regulated by targeting survivin
Summary
Lung cancer is one of the deadliest cancers worldwide. More than 1.5 million people die from lung cancer each year. New chemotherapy drugs enter the market every year, the adverse reactions and toxicity of these drugs have become a bottleneck in the treatment of clinical lung cancer [3]. It is necessary to develop new treatment strategies to prevent the metastasis of lung adenocarcinoma. Survivin inhibits the activation of caspases by binding to X-linked inhibitor of apoptosis (XIAP) protein, thereby inhibiting the apoptosis of cancer cells. Many studies have reported the antitumor activity of different Chinese medicines, revealing novel pathways for natural pharmacological compounds to prevent cancer. Lithospermum erythrorhizon has various pharmacological effects, including anti-inflammatory, antibacterial, and anticough effects. Researchers have isolated various active ingredients from Lithospermum erythrorhizon, including shikonin, acetylshikonin, and isobutylshikonin. This study investigated the antitumor activity of shikonin in lung cancer cells H1299 and explored its antitumor molecular mechanism
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