Wenting Deng1, Wei Han2, Tao Fan3, Xiaoku Wang3, Zhao Cheng3, Bo Wan3, Jinlian Chen3. 1. College of Pharmacy, Xi'an Medical University, No. 1 Xinwang Road of Weiyang District, 710021, Xi'an, Shaanxi, China. Electronic address: dengwenting209@163.com. 2. Department of Medical Equipment, Shaanxi Provincial People's Hospital, No. 256 Youyi West Road, 710068, Xi'an, Shaanxi, China. 3. College of Pharmacy, Xi'an Medical University, No. 1 Xinwang Road of Weiyang District, 710021, Xi'an, Shaanxi, China.
Abstract
BACKGROUND: Scutellarin is a naturally flavone glycoside that has been shown to exhibit anti-proliferative and anti-apoptotic activities among various human malignancies. However, the anti-cancer effect of Scutellarin in Renal cell carcinoma (RCC) and the underlying mechanism remains unclear. METHODS AND MATERIALS: RCC cell lines ACHN and 786-O were treated with different concentrations (0-210 μM) of Scutellarin in vitro. Cell viability and proliferation were investigated by MTT and colony formation assays. Cell invasion and migration were detected by Transwell assays. Cell apoptosis and cell cycle distribution was measured by flow cytometry. Western blot was used to investigate the expression levels of crucial proteins. Xenograft tumor model was established to evaluate tumor growth in vivo. RESULTS: Scutellarin significantly inhibited RCC cell proliferation in a dose- and time- dependent manner. Treatment of RCC cells with Scutellarin (30, 60, and 90 μM) markedly induced apoptosis and cell cycle arrested at G0/G1 phase in a concentration-dependent characteristic. Cell invasion and migration capacities of RCC cells were also dose-dependently suppressed by Scutellarin treatment. Western blot assays revealed that the crucial proteins including cyclin D1, CDK2, Bcl2, MMP-2, and MMP-9 were significantly reduced while Bax, cleaved caspase 3 and p21 were increased by Scutellarin in RCC cells. In vivo assay indicated that Scutellarin possessed anti-cancer effect on xenograft without triggering toxic effect. Mechanically, Scutellarin dramatically increased the protein level of phosphatase and tensin homologue (PTEN) and inhibited the activity of P13K/AKT/mTOR signaling. Ectopic expression of PTEN enhanced the inhibitory effect of Scutellarin on RCC proliferation while knockdown of PTEN abrogated it through regulating its downstream P13K/AKT/mTOR signaling pathway. CONCLUSION: Scutellarin inhibited RCC cell proliferation and invasion partially by enhancing the expression of PTEN through inhibition of P13K/AKT/mTOR pathway, suggesting that Scutellarin might serve as a potential therapeutic agent in RCC treatment.
BACKGROUND:Scutellarin is a naturally flavone glycoside that has been shown to exhibit anti-proliferative and anti-apoptotic activities among various humanmalignancies. However, the anti-cancer effect of Scutellarin in Renal cell carcinoma (RCC) and the underlying mechanism remains unclear. METHODS AND MATERIALS: RCC cell lines ACHN and 786-O were treated with different concentrations (0-210 μM) of Scutellarin in vitro. Cell viability and proliferation were investigated by MTT and colony formation assays. Cell invasion and migration were detected by Transwell assays. Cell apoptosis and cell cycle distribution was measured by flow cytometry. Western blot was used to investigate the expression levels of crucial proteins. Xenograft tumor model was established to evaluate tumor growth in vivo. RESULTS:Scutellarin significantly inhibited RCC cell proliferation in a dose- and time- dependent manner. Treatment of RCC cells with Scutellarin (30, 60, and 90 μM) markedly induced apoptosis and cell cycle arrested at G0/G1 phase in a concentration-dependent characteristic. Cell invasion and migration capacities of RCC cells were also dose-dependently suppressed by Scutellarin treatment. Western blot assays revealed that the crucial proteins including cyclin D1, CDK2, Bcl2, MMP-2, and MMP-9 were significantly reduced while Bax, cleaved caspase 3 and p21 were increased by Scutellarin in RCC cells. In vivo assay indicated that Scutellarin possessed anti-cancer effect on xenograft without triggering toxic effect. Mechanically, Scutellarin dramatically increased the protein level of phosphatase and tensin homologue (PTEN) and inhibited the activity of P13K/AKT/mTOR signaling. Ectopic expression of PTEN enhanced the inhibitory effect of Scutellarin on RCC proliferation while knockdown of PTEN abrogated it through regulating its downstream P13K/AKT/mTOR signaling pathway. CONCLUSION:Scutellarin inhibited RCC cell proliferation and invasion partially by enhancing the expression of PTEN through inhibition of P13K/AKT/mTOR pathway, suggesting that Scutellarin might serve as a potential therapeutic agent in RCC treatment.
Authors: Liu-Lin Xiong; Ruo-Lan Du; Lu-Lu Xue; Ya Jiang; Jin Huang; Li Chen; Jia Liu; Ting-Hua Wang Journal: Chin Med Date: 2020-03-26 Impact factor: 5.455
Authors: Jose Antonio Ma G Garrido; Krizelle Mae M Alcantara; Joshua Miguel C Danac; Fidel Emmanuel C Serrano; Eva Maria Cutiongco-de la Paz; Reynaldo L Garcia Journal: Cells Date: 2021-12-05 Impact factor: 6.600