Scutellarin inhibits human renal cancer cell proliferation and migration via upregulation of PTEN.

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. 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. 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. 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.

Deng W ，Han W ，Fan T ，Wang X ，Cheng Z ，Wan B ，Chen J ... -  《-》

Scutellarin inhibits the invasive potential of malignant melanoma cells through the suppression epithelial-mesenchymal transition and angiogenesis via the PI3K/Akt/mTOR signaling pathway.

Malignant melanoma is the leading cause of death from skin disease, due in large part to its propensity to metastasize. Scutellarin is an active flavone extracted from traditional Chinese herb Erigeron breviscapus (Vant.) Hand. Mazz. Recent studies have reported that scutellarin can be utilized to treat various types of tumors. In this study, we investigated the effects of scutellarin on melanoma cancer cell invasive potential and the molecular mechanisms underlying these effects using A375 melanoma cells lines. The in-vitro antitumor activity of scutellarin was evaluated by CCK-8 assay, wound-healing assay, transwell assays, adhesion assays, and tube formation assays to assess the cell viability, migration, invasion, adhesion, and angiogenesis, respectively. Also, western blotting assay was used to assess the level of PI3K/Akt/mTOR signaling pathway proteins in A375 cells. We found that scutellarin significantly inhibited melanoma cell lines and HUVECs viability in a time- and concentration-dependent manners. Additionally, scutellarin effectively suppressed tumor cell migration, invasion, adhesion through the suppression of EMT and angiogenesis by inhibiting the PI3K/Akt/mTOR signaling pathway. These results indicated that scutellarin could markedly inhibit the invasive potential of melanoma cell lines by suppressing the EMT and angiogenesis through the PI3K/Akt/mTOR signaling pathway. It suggests that scutellarin might be a potential compound in malignant melanoma treatment.

Li CY ，Wang Q ，Wang X ，Li G ，Shen S ，Wei X ... -  《-》

Scutellarin suppresses migration and invasion of human hepatocellular carcinoma by inhibiting the STAT3/Girdin/Akt activity.

Scutellarin is an active flavone from Erigeron breviscapine (vant) Hand Mass. This study aimed to investigate the potential role of scutellarin in migration and invasion of human hepatocellular carcinoma (HCC) cells and its possible mechanism. In comparison with the vehicle-treated controls, treatment with scutellarin (50 mg/kg/day) for 35 days significantly mitigated the lung and intrahepatic metastasis of HCC tumors in vivo. Scutellarin treatment significantly reduced HepG2 cell viability in a dose-dependent manner, and inhibited migration and invasion of HCC cells in vitro. Scutellarin treatment significantly reduced STAT3 and Girders of actin filaments (Girdin) expression, STAT3 and Akt phosphorylation in HCC cells. Introduction of STAT3 overexpression restored the scutellarin-downregulated Girdin expression, Akt activation, migration and invasion of HCC cells. Furthermore, induction of Girdin overexpression completely abrogated the inhibition of scutellarin on the Akt phosphorylation, migration and invasion of HCC cells. Scutellarin can inhibit HCC cell metastasis in vivo, and migration and invasion in vitro by down-regulating the STAT3/Girdin/Akt signaling.

Ke Y ，Bao T ，Wu X ，Tang H ，Wang Y ，Ge J ，Fu B ，Meng X ，Chen L ，Zhang C ，Tan Y ，Chen H ，Guo Z ，Ni F ，Lei X ，Shi Z ，Wei D ，Wang L ... -  《-》

Apoptosis induced by the methanol extract of Salvia miltiorrhiza Bunge in non-small cell lung cancer through PTEN-mediated inhibition of PI3K/Akt pathway.

Salvia miltiorrhiza Bunge, a well-known traditional Chinese medicinal (TCM) plant, has been used to treat cardiovascular diseases since thousands of years. Many studies reported that the active component tanshinones displayed a variety of biological activities: anti-thrombous, anti-allergic, anti-inflammatory, antioxidant and anti-tumor promoting. But the mechanism of how the active components working still need to be clarified. The anti-tumor effect of compounds of tanshinone (CTN), the methanol extract of Salvia miltiorrhiza Bunge roots, was investigated. The aim of this study was to investigate the effects of CTN on the growth inhibition, apoptosis and molecular targets of human non-small cell lung cancer (NSCLC). CTN-induced cytotoxicity was determined by MTT assay. The cell survival was evaluated using clonogenic survival assay. The morphology of Glc-82 cells after treatment with CTN was determined by fluorescence microscopy. Cell cycle distribution was revealed by flow cytometry. The apoptotic cells were quantified with annexin V-FITC/PI staining and flow cytometry, and observed using Hoechst 33258 staining and TUNEL assays. The expression levels of proteins were analyzed using western blot. Tumor growth was assessed by subcutaneous inoculation of cells into BALB/c nude mice. CTN inhibited the proliferation of NSCLC in a dose-dependent manner and induced both early and late apoptosis. Treatment of Glc-82 cells with CTN (5-80μg/ml) significantly (p<0.05) suppressed the cell proliferation in a concentration and time-dependent manner. CTN induced significant (p<0.05) and dose-dependent apoptosis of Glc-82 cells. Cell cycle assay showed that CTN induced a G2/M phase arrest, and significantly (p<0.05) increased expression of p53 and p21, actived caspase-3/9 and PARP1, which suggest the involvement of the mitochondria in the apoptotic signals. In addition, CTN decreased expression of the anti-apoptotic protein Bcl-2, Bcl-xl and increased expression of the pro-apoptotic protein Bax. Result also showed that CTN could increase expression levels of PTEN, and reduce the phosphorylated levels of Akt (protein kinase B) on Thr 308 and Ser 473 domain. In vivo assay showed that the antitumor effect of CTN was significantly augmented without increasing toxicity in nude mice bearing Glc-82 xenograft. The PTEN/Akt signaling axis is defined as a critical pathway regulated by PTEN in NSCLC. CTN, the methanol extract of Salvia miltiorrhiza Bunge, are the active compounds as shown by their ability to induce apoptosis through the mitochondrial pathway of apoptosis and PTEN-mediated inhibition of PI3K/Akt pathway. CTN could inhibit tumor growth more efficiently, which supports the ethno-medicinal use of this herb as an alternative or complementary therapy for NSCLC.

Ye YT ，Zhong W ，Sun P ，Wang D ，Wang C ，Hu LM ，Qian JQ ... -  《-》

Depletion of the triggering receptor expressed on myeloid cells 2 inhibits progression of renal cell carcinoma via regulating related protein expression and PTEN-PI3K/Akt pathway.

Zhang H ，Sheng L ，Tao J ，Chen R ，Li Y ，Sun Z ，Qian W ... -  《-》