Cancer stem cells are considered to be one of the causes of cancer. In recent years, stemness (stem like) of gene expression patterns in the development process of cancer has been observed. Stemness and pathology of cancer are closely related. Elucidation of the stemness regulation of cancer is an important key to the development of new cancer prevention methods. However, as far as we know, there exist no cancer prevention studies focusing on cancer stem cells. In this study, we have investigated the possibility of prostate cancer prevention with a focus on cancer stem cells. We utilized prostate cancer cell lines PC3, DU145 (androgen-independent) and LNCaP (androgen-dependent) cells. Then, using spheroid formed cells, mRNA expression levels of cancer stem cells markers were estimated by RT-real time-PCR. Cancer cells have several malignant phenotypes under hypoxia, and we investigated for the cancer stem cells induced malignant alteration under hypoxia. In addition, under hypoxia, we investigated cell viability effect under tocotrienol-rich fraction (TRF) from annatto. TRF almost consists of delta- tocotrienol (δ-T3) that has the strongest anti-cancer activity. We observed spheroid formation capacity and compared the spheroid sizes and mRNA levels of DU145, PC3 and LNCaP cells. Size of DU145 spheroid is smaller in comparison to spheroids of PC3 and LNCaP. mRNA expression levels of cancer stem cells marker were elevated in PC3 and LNCaP cells. This means that PC3 and LNCaP cells have higher concentration of cancer stem cells. Furthermore, stemness decreases with increase of passage number, the number of cultures. We confirmed the presence of stemness in the formation capacity of spheroid until passage 4. Under hypoxia, cell viability of cancer stem cells was elevated compared to normal cultured prostate cancer cells. In addition, under hypoxia and TRF treatment, cell viability of cancer stem cells decreased with increase in TRF concentration compared to control (0 μg/ml). Our results suggest that TRF suppress cell viability of prostate cancer stem cells under hypoxic states and is effective in prostate cancer prevention.

Citation Format: Nobuya Shiozawa, Ryosuke Sugahara, Ayami Sato, Masako Ota, Tomohiro Yano. Possibility of prostate cancer prevention based on cancer stem cell theory. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2624.