Scutellarin Increases Cisplatin-Induced Apoptosis and Autophagy to Overcome Cisplatin Resistance in Non-small Cell Lung Cancer via ERK/p53 and c-met/AKT Signaling Pathways

Frontiers in Pharmacology
Chao-Yue SunBing Feng

Abstract

Cisplatin, as the first-line anti-tumor agent, is widely used for treatment of a variety of malignancies including non-small cell lung cancer (NSCLC). However, the acquired resistance has been a major obstacle for the clinical application. Scutellarin is a active flavone extracted fromErigeron breviscapus Hand-Mazzthat has been shown to exhibit anticancer activities on various types of tumors. Here, we reported that scutellarin was capable of sensitizing A549/DDP cells to cisplatin by enhancing apoptosis and autophagy. Mechanistic analyses indicated that cisplatin-induced caspase-3-dependent apoptosis was elevated in the presence of scutellarin through activating extracellular signal-regulated kinases (ERK)-mediated p53 pathway. Furthermore, scutellarin also promoted cisplatin-induced cytotoxic autophagy, downregulated expression of p-AKT and c-met. Deficiency of c-met reduced p-AKT level, and inhibition of p-AKT or c-met improved autophagy in A549/DDP cells. Interestingly, loss of autophagy attenuated the synergism of this combination.In vivo, the co-treatment of cisplatin and scutellarin notably reduced the tumor size when compared with cisplatin treatment alone. Notably, scutellarin significantly reduced the toxicity generat...Continue Reading

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Citations

Oct 26, 2018·Cancer Chemotherapy and Pharmacology·Chao-Yue SunBing Feng
Jun 28, 2019·Frontiers in Oncology·Qingmei YeRen-Wang Jiang
Jul 24, 2020·Pharmacological Reports : PR·Tanweer HaiderVandana Soni
Feb 14, 2019·Journal of Experimental & Clinical Cancer Research : CR·Muli WuduXueshan Qiu
Nov 17, 2020·Frontiers in Oncology·Jose G Alvarez-MeythalerMatilde E LLeonart
Nov 18, 2020·Biochemistry. Biokhimii︠a︡·A A DaksN A Barlev
Feb 19, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zhang LiLi Gaofeng
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Luis Gustavo Saboia PonteFernando Moreira Simabuco
Jun 8, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Panpan LvWenyuan Gao
Feb 24, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Chao-Yue SunBing Feng

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Methods Mentioned

BETA
Assay
electrophoresis
Xenograft
flow cytometry

Software Mentioned

ImageJ
CalcuSyn

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