Abstract
BackgroundAtractylenolide I (ATR-1), an active component of Rhizoma Atractylodis Macrocephalae, possesses cytotoxicity against various carcinomas. However, little is known about the effects of ATR-1on bladder cancer. In the present study, the anti-tumor activity of ATR-1 was examined on bladder cancer cells both in vivo and in vitro.MethodsMTT assay was used to assess the cytotoxic effect of ATR-1. Cell cycle distribution and apoptosis levels were evaluated using flow cytometry. Western blotting assay was applied to measure the levels of proteins associated with the apoptotic pathway, cell cycle progression and PI3K/Akt/mTOR signaling pathway. Tumor models in nude mice were induced by injection of T-24 and 253J human bladder cancer cells.ResultsATR-1 inhibited bladder cancer cell proliferation, arrested cell cycle in G2/M phase through up-regulation of p21 and down-regulation of cyclin B1, CDK1 and Cdc25c. Meanwhile, ATR-1 also triggered cellular apoptosis depending on the activation of mitochondrial apoptotic pathway. Mechanism investigation indicated that ATR-1 exerts its anti-tumor effect also relies on the inhibition of PI3K/Akt/mTOR signaling pathway. Finally, mice studies showed that ATR-1 blocked the T-24 or 253J-induced xenograft tumor growth without noticeable toxicity.ConclusionsATR-1 may be served as a potential therapeutic agent for the treatment of bladder cancer.
Highlights
Atractylenolide I (ATR-1), an active component of Rhizoma Atractylodis Macrocephalae, possesses cytotoxicity against various carcinomas
ATR-1 suppresses proliferation of bladder cancer cells lines The anti-proliferative activity of ATR-1 was initially evaluated by using four human bladder cancer cell lines RT4, 5637, 253J and T-24
Cells were exposed to various concentrations of ATR-1 for 48 h, and the cell viabilities were measured by Methyl thiazolyl diphenyl tetrazolium bromide (MTT) assay
Summary
Atractylenolide I (ATR-1), an active component of Rhizoma Atractylodis Macrocephalae, possesses cytotoxicity against various carcinomas. Little is known about the effects of ATR-1on bladder cancer. The anti-tumor activity of ATR-1 was examined on bladder cancer cells both in vivo and in vitro. Bladder cancer is the second most common urological malignancies with an estimated 429,000 new cases and 165,000 deaths every year [1]. Most bladder cancer cases are superficial and treated with transurethral resection in the clinic. Current treatments to bladder cancer have high recurrence rates and may cause strong side effects [3]. Great efforts have been made in the treatment of bladder cancer over past decades, it still remains as a major health concern and new therapeutic approaches are urgently required [4]. Natural products have attracted great attentions for identifying new anti-tumor agents due to
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