Annatto Tocotrienol Induces a Cytotoxic Effect on Human Prostate Cancer PC3 Cells via the Simultaneous Inhibition of Src and Stat3.

Prostate cancer is one of the most frequently occurring cancers and often acquires the potential of androgen-independent growth as a malignant phenotype. Androgen-independent prostate cancer has severe chemoresistance towards conventional chemotherapeutic agents, so a new treatment approach is required for curing such prostate cancer. In this context, the present study was undertaken to check if annatto tocotrienol (main component δ-tocotrienol) could suppress cell growth in human prostate cancer (PC3, androgen-independent type) cells via the inhibition of Src and Stat3. The tocotrienol showed cytotoxic effects on PC3 cells in a dose-dependent manner, and the effect depended on G1 arrest in the cell cycle and subsequent induction of apoptosis. In a cytotoxic dose, the tocotrienol suppressed cellular growth via the simultaneous inhibition of Src and Stat3. Similarly, the treatment combination of both Src and Stat3 inhibitors induced cytotoxic effects in PC3 cells in an additive manner compared to each by itself. With respect to cell cycle regulation and the induction of apoptosis, the combination treatment showed a similar effect to that of the tocotrienol treatment. These results suggest that annatto tocotrienol effectively induces cytotoxicity in androgen-independent prostate cancer cells via the suppression of Src and Stat3.

Efficient approach for simultaneous estimation of multiple health-promoting effects of foods.

The investigation of new food constituents for purposes of disease prevention or health promotion is an area of increasing interest in food science. This paper proposes a new system that allows for simultaneous estimation of the multiple health-promoting effects of food constituents using informatics. The model utilizes expression data of intracellular marker proteins as descriptors that reply to stimulation of a constituent. To estimate three health-promoting effects, namely, cancer cell growth suppression activity, antiviral activity, and antioxidant stress activity, each model was constructed using expression data of marker proteins as input data and health-promoting effects as the output value. When prediction performances of three types of mathematical models constructed by simple, multiple regressions, or artificial neural network (ANN), were compared, the most adequate model was the one constructed using an ANN. There were no statistically significant differences between the actual data and estimated values calculated by the ANN models. This system was able to simultaneously estimate health-promoting effects with reasonable precision from the same expression data of marker proteins. This novel system should prove to be an interesting platform for evaluation of the health-promoting effects of food.

Novel deletion spanning RCC1-like domain of RPGR in Japanese X-linked retinitis pigmentosa family.

PURPOSE: To describe a macrodeletion spanning entire RCC1-like doman in the RPGR gene in one Japanese family with X-linked retinitis pigmentosa (XLRP). METHODS: Clinical ophthalmologic examinations were performed and genomic DNA was extracted from blood samples. Genomic DNA was analyzed by Southern blot and PCR amplification with specific primers. RESULTS: Patients had severe symptoms with early onset and rapid deterioration. PCR amplification and Southern blot analysis revealed the absence of the 5' half of the RPGR gene. The deletion was confirmed and characterized by designing flanking PCR primers: the deletion start point was located 80 bp upstream of the translation start site in exon 1, the end point was 42 bp downstream of exon 11. CONCLUSIONS: This 30 kb deletion contains the exons coding for the RCC1-like domain of RPGR. It is the first report of a macrodeletion that spans the entire RCC1-like domain of RPGR in X-linked retinitis pigmentosa patients, and suggests that loss of function of this domain disrupts the function of RPGR in human retina.