A new strategy to prevent prostate cancer stem cells

[Speaker] Saki Kaneko:1
[Co-author] Tomohiro Yano:1
1:Graduate School of Food and Nutritional Science, Toyo University, Japan

In this study, we show a new strategy to eradicate cancer stem cells in two steps.
Cancer stem cells are assumed as a main cause of oncogenesis and recurrent cancer. Especially, resistance to anti-cancer drug is a severe therapeutic problem. However, there is no effective prevention and treatment strategy against cancer stem cells. Soybean is known as a cancer-preventive food. The most predominant protease inhibitor in soybeans is the Bowman-Birk inhibitor (BBI) which is a well-established cancer chemo preventive agent due to its strong anti-carcinogenic activity. Our prevention study has shown that BBI induces connexin43 (Cx43) which is a tumor suppressor gene and that forms gap junction. Through the gap junction, it can restore normal cell functions. This is the cancer suppression effect of BBI. On the other hand, it is known that mitocan has strong cancer suppression effect by targeting affection the mitochondria, so we focused on alpha-Tocopherol (TOS) as a mitocan. Our aim is to propose a new preventive strategy targeting on prostate cancer stem cells by combining of BBI and TOS.
Androgen-dependent prostate cancer cells (LNCaP) were used. And then, we made spheroid-formed cancer stem cells (CSCs) from LNCaP parental cells. Cell viability was evaluated by a WST-1 assay. Level of mRNA was determined by RT-Real time PCR.
Level of Cx43 mRNA was increased by BBI with a statistical significance(p<0.01). In parallel with the Cx43 induction, cell viability was inhibited in a dose-dependent manner and some markers of CSCs and chemo-resistance was decreased.
Additionally, BBI drastically cancelled expression of androgen receptor (AR), androgen independency and chemo-resistance in CSCs. Therefore, the combination has suppressive effect on cancer stem cells.

Herein, we propose a new strategy targeting cancer stem cells. First, BBI induces the differentiation and decreases the characteristics of cancer stem cells. And then, CSCs which are induced differentiation are suppressed by TOS.

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