著者

Chiaki SATO Saki KANEKO Ayami SATO Nantiga VIRGONA Kozue NAMIKI Tomohiro YANO

出版者

Center for Academic Publications Japan

雑誌

Journal of Nutritional Science and Vitaminology (ISSN:03014800)

巻号頁・発行日

vol.63, no.5, pp.349-354, 2017 (Released:2017-12-08)

参考文献数

29

被引用文献数

9 29

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Tocotrienols (T3s) and tocopherols (Tocs) are both members of the vitamin E family. It is known that δ-tocotrienol (δ-T3) has displayed the most potent anti-cancer activity amongst the tocotrienols. On the other hand, γ-tocopherol (γ-Toc) is reported to have a protective effect against prostate cancer. Therefore, we investigated whether the combination of γ-Toc and δ-T3 could strengthen the inhibitory effect of δ-T3 on prostate cancer cell growth. In this study the effect of combined δ-T3 (annatto T3 oil) and γ-Toc (Tmix, γ-Toc-rich oil) therapy was assessed against human androgen-dependent prostate cancer cells (LNCaP). We found that combined treatment of δ-T3 (10 μM) and γ-Toc (5 μM) resulted in reinforced anti-prostate cancer activity. Specifically, cell cycle phase distribution analysis revealed that in addition to G1 arrest caused by the treatment with δ-T3, the combination of δ-T3 with γ-Toc induced G2/M arrest. Enhanced induction of apoptosis by the combined treatment was also observed. These findings indicate that combination of δ-T3 and γ-Toc significantly inhibits prostate cancer cell growth due to the simultaneous cell cycle arrest in the G1 phase and G2/M phase.

著者

Saki KANEKO Takumi YAMAZAKI Kakeru KOHNO Ayami SATO Kazunori KATO Tomohiro YANO

出版者

Center for Academic Publications Japan

雑誌

Journal of Nutritional Science and Vitaminology (ISSN:03014800)

巻号頁・発行日

vol.65, no.3, pp.272-277, 2019-06-30 (Released:2019-06-30)

参考文献数

26

被引用文献数

4

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The reoccurrence of androgen-dependent prostate cancer after anti-androgen therapy mainly depends on prostate cancer stem-like cells. To reduce the risk, it is important to delete the cancer stem-like cells. Furthermore, to induce differentiation of cancer stem-like cells is critical to abrogate stemness of the cells. Therefore, we tried to investigate a possibility on the establishment of a new effective therapy to eradicate the cancer stem-like cells via the induction of differentiation in this study. Prostate cancer stem-like cells from an androgen-dependent prostate cancer cell line (LNCaP cell) had severe resistance against an anti-androgen therapeutic agent. We selected Bowman-Birk inhibitor (BBI) from soybeans reported as a chemopreventive agent in prostate cancer to differentiate the caner stem-like cells and α-tocopheryl succinate (TOS) known as a mitocan to induce effectively cytotoxic effect against the cancer stem-like cells. In fact, only TOS treatment had cytotoxic effect against the cancer stem-like cells, but the addition of BBI treatment to the cells treated with TOS reinforced TOS-mediated cytotoxicity in the cancer stem-like cells. This reinforcement coincided with the combination-enhanced apoptosis in the stem-like cells. Also, we confirmed caspase9-caspase3 cascade mainly contributed to the enhancement of the cytotoxicity in the stem-like cells caused by the combination, indicating that the reinforcement of BBI on TOS-mediated apoptosis via mitochondria related to the enhancing cytotoxic effect of the combination on the prostate cancer stem-like cells. Overall, it seems that the combination is an effective new approach to reduce the reoccurrence of prostate cancer targeting prostate cancer stem cells.