Cytotoxic and chemosensitization effects of Scutellarin from traditional Chinese herb Scutellaria altissima L. in human prostate cancer cells

Abstract

Scutellaria altissima L. is a common traditional Chinese medicine used to treat inflammation in some countries. Scutellarin, an active major flavone glycoside isolated from the traditional Chinese medicine Scutellaria altissima L., has been shown to offer various beneficial biochemical effects on cerebrovascular diseases and inflammation. However, the antiproliferative effects of Scutellarin in prostate cancer and the underlying mechanism are not fully elucidated. In the present study, we aimed to ascertain whether Scutellarin inhibits cancer cell growth and to further explore the molecular mechanism. Scutellarin enhanced the sensitivity of prostate cancer cells to cisplatin. MTT assays revealed that cell viability was significantly decreased in the prostate cancer cells treated with Scutellarin. Flow cytometric analysis indicated that Scutellarin suppressed cell proliferation by promoting G2/M arrest and inducing apoptosis. We employed western blotting to delineate the underlying mechanisms involved in the G2/M arrest and apoptosis. Comet assay and γH2AX immunocytochemistry were used to detect levels of DNA damage in PC3 cells exposed to Scutellarin and/or cisplatin. Our data revealed that Scutellarin significantly induced prostate cancer cell apoptosis by activating the caspase cascade. An increase in the Bax/Bcl-2 ratio, depolarization of mitochondrial membrane potential and cell cycle arrest at G2/M phase were accompanied by the apoptosis induction. Additionally, Scutellarin altered the protein expression of cell cycle and apoptosis regulatory genes by downregulating Cdc2, cyclin B1 and Bcl-2 and upregulating caspase-3, caspase-9 and Bax in prostate cancer cells. Furthermore, Scutellarin sensitized PC3 cells to cisplastin treatment in a dose-dependent manner. Taken together, our data confirmed the cytotoxicity of Scutellarin against prostate cancer PC3 cells and provide new findings in regards to Scutellarin sensitizing prostate cancer cells to chemotherapy. Our findings suggest that Scutellarin has potential to be used as a novel antineoplastic therapeutic candidate for prostate cancer patients.

Scutellarin suppresses proliferation and promotes apoptosis in A549 lung adenocarcinoma cells via AKT/mTOR/4EBP1 and STAT3 pathways

“…reported that SCU effectively inhibits hepatocellular carcinoma metastasis in vivo and the migration and invasion of hepatocellular carcinoma cells in vitro . Other researchers have reported that SCU induces apoptosis and G2/M arrest, inhibits cell proliferation of prostate cancer PC3 cells, and sensitizes the cells to chemotherapy …”

“…21 Other researchers have reported that SCU induces apoptosis and G2/M arrest, inhibits cell proliferation of prostate cancer PC3 cells, and sensitizes the cells to chemotherapy. 16 In this study, we first investigated the toxicity of SCU to A549 lung adenocarcinoma cells. Using CCK-8 and colony formation assays, our results show that SCU effectively suppresses the proliferation of A549 cells.…”

“…Substantial evidence has confirmed that SCU, a flavonoid isolated from Erigeron breviscapus (Vant.) Hand.‐Mazz., has antitumor effects on several cancers, including liver, colorectal, breast, and prostate, as well as lymphomas . However, little is known about its antitumor mechanisms and whether SCU can inhibit NSCLC when used alone.…”

“…Hand.-Mazz., has antitumor effects on several cancers, including liver, colorectal, breast, and prostate, as well as lymphomas. [15][16][17][18][19] However, little is known about its antitumor mechanisms and whether SCU can inhibit NSCLC when used alone. In the present study, we explored the effects of different concentrations of SCU on proliferation, apoptosis, and tumorigenesis, and the expression of AKT/mTOR/4E-BP1 and STAT3 signaling pathway proteins in cultured A549 lung cancer cells.…”

Anti-Prostate Cancer Activity of Plant-Derived Bioactive Compounds: a Review

“…Prominent constituents of this family include flavonoids, phenolic acids, lipophilic tanshinones , sesquiterpenoids, diterpenoids, and triterpenoids. Nepeta cataria, Scutellaria altissima, Salvia miltiorrhiza, Salvia chorassanica, and Salvia miltiorrhiza, all members of the Lamiaceae family exhibited cytotoxic effects on DU145, PC-3, or LNCaP prostate cancer cells and induced cell cycle arrest and subsequent apoptosis via a variety of mechanisms [28,[41][42][43][44]. PC-3 cells treated with extract from Scutellaria altissima, which contains predominantly scutellarin, a flavone glycoside, arrest in the GAP2/mitotic phase as a result of the increased expression of cyclin B1 and Cdc2 [43].…”