Abstract
Sepia ink oligopeptide (SIO) is a tripeptide extracted from Sepia ink. To test the hypothesis that SIO inhibits prostate cancer by inducing apoptosis, the effects of SIO on the proliferation of three human prostate cancer cell lines were examined using a CCK-8 assay. SIO significantly inhibited the proliferation of DU-145, PC-3 and LNCaP cells in a time- and dose-dependent manner. Flow cytometry studies showed that exposing DU-145, PC-3 and LNCaP cells to 5, 10, or 15 mg/mL SIO for 24 h increased the percentage of the early-stage apoptotic cells from 11.84% to 38.26% (DU-145), 22.76% to 39.96% (PC-3) and 5.05% to 16.11% (LNCaP), respectively. In addition, typical morphologic changes were observed in the cells with acridine orange/ethidium bromide staining. SIO treatment induced strong S and G2/M phase cell cycle arrest in a dose-dependent manner in DU-145 and LNCaP. In contrast, SIO treatment induced strong Sub G1 and G0/G1 phase cell cycle arrest in a dose-dependent manner in PC-3. SIO exposure for 24 h decreased the expression of the anti-apoptotic protein Bcl-2 and increased the expression of the apoptogenic protein Bax. Moreover, the Bax/Bcl-2expression ratio was increased. Concurrently, the expression of caspase-3 was upregulated. These data support our hypothesis that SIO has anticarcinogenic properties.
Highlights
Prostate cancer is the second most frequently diagnosed cancer and the sixth leading cause of cancer death in men, accounting for 14% (903,500) of the total new cancer cases and 6% (258,400) of the total cancer deaths in men in 2008 [1]
The anti-proliferative effects of Sepia ink oligopeptide (SIO) on human prostate cancer DU-145, PC-3 and LNCaP cells were first investigated by CCK-8 assay
Western Blotting Results of Bcl-2, Bax and Caspase-3 in DU-145, PC-3 and LNCaP Cells Treated with SIO
Summary
Prostate cancer is the second most frequently diagnosed cancer and the sixth leading cause of cancer death in men, accounting for 14% (903,500) of the total new cancer cases and 6% (258,400) of the total cancer deaths in men in 2008 [1]. Treatment for prostate cancer may include active surveillance (monitoring for tumor progression or symptoms), surgery, radiation therapy, high-intensity focused ultrasound, chemotherapy, cryosurgery, hormonal therapy, or various combinations of these [5,6,7]. Dolastatins-10 and -15 are peptides isolated from the marine sea hare Dolabella auricularia, which have been known to have antitumor activities in several cancer cell lines [15,16]. Our previous study [19] demonstrated that SIO significantly inhibits the proliferation of DU-145 cells and induces their death in a dose-dependent manner in vitro. The antitumor mechanisms of SIO against prostate cancer, are unclear. We evaluated the anticancer activity and related mechanisms of SIO against prostate cancer in cell culture
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