J Cancer 2018; 9(18):3247-3256. doi:10.7150/jca.25921

Research Paper

Scutellarin induces apoptosis and autophagy in NSCLC cells through ERK1/2 and AKT Signaling Pathways in vitro and in vivo

ChaoYue Sun1, CaiYun Li1, XiaoFeng Li2, Ying Zhu1, ZuQing Su1, XieQi Wang1, QingLian He1, GuangJuan Zheng1✉, Bing Feng1✉

1. Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510120, China.
2. Clinical Medical College of Acupuncture and Rehabilitation, Guangzhou University of Chinese Medicine, no 232, Waihuandong Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, China.

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Sun C, Li C, Li X, Zhu Y, Su Z, Wang X, He Q, Zheng G, Feng B. Scutellarin induces apoptosis and autophagy in NSCLC cells through ERK1/2 and AKT Signaling Pathways in vitro and in vivo. J Cancer 2018; 9(18):3247-3256. doi:10.7150/jca.25921. Available from http://www.jcancer.org/v09p3247.htm

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Curative molecular therapy for non-small cell lung cancer (NSCLC) is still lacking. Scutellarin, an active flavone extracted from Erigeron breviscapus Hand-Mazz, displays anti-tumor property in diverse cancer types, yet its tumor-suppressive effect on NSCLC is not reported. In this study, we found that scutellarin significantly inhibited the proliferation of NSCLC cells, induced cell apoptosis, and triggered autophagy. Notably, inhibition of autophagy with inhibitor HCQ attenuated the anti-proliferative activity of scutellarin, indicating that scutellarin-induced autophagy is antineoplastic. In addition, HCQ treatment reduced scutellarin-induced apoptosis. Further study demonstrated that scutellarin stimulated phosphorylation of ERK1/2, and inhibition of ERK1/2 with inhibitor U0126 markedly attenuated scutellarin-induced autophagy. Similarly, scutellarin downregulated the expression of p-AKT, and AKT inhibitor MK-2206 induced autophagy. Moreover, there also existed crosstalk between ERK and AKT pathways. Finally, in vivo xenograft nude mice experiment proved that scutellarin treatment significantly reduced tumor growth and increased the levels of LC3-II and p-ERK1/2, suppressed p-AKT in mice tumors. Thus, our study for the first time uncovered the anti-cancer function of scutellarin on NSCLC cells, and might provide a potential novel therapy for treatment of patients with NSCLC.

Keywords: Scutellarin, NSCLC, apoptosis, autophagy, ERK1/2, AKT