title: Annatto Tocotrienol Induces a Cytotoxic Effect on Human Prostate Cancer PC3 Cells via the Simultaneous Inhibition of Src and Stat3.
abstract: 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.
authors.affiliation: Graduate School of Life Sciences, Toyo University.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Sugahara
authors.forename: Ayami
authors.initials: A
authors.lastname: Sato
authors.forename: Asuka
authors.initials: A
authors.lastname: Uchida
authors.forename: Shinya
authors.initials: S
authors.lastname: Shiozawa
authors.forename: Chiaki
authors.initials: C
authors.lastname: Sato
authors.forename: Nantiga
authors.initials: N
authors.lastname: Virgona
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yano
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D031212:Bixaceae / Q000737:chemistry*; D002338:Carotenoids / Q000737:chemistry*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D016391:Genes, src; D006801:Humans; D008297:Male; D010936:Plant Extracts / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D024508:Tocotrienols / Q000494:pharmacology / Q000627:therapeutic use*; D014810:Vitamin E / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D014815:Vitamins / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D010936:Plant Extracts; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D024508:Tocotrienols; D014815:Vitamins; D014810:Vitamin E; C082097:tocotrienol, delta; D002338:Carotenoids; C054041:annatto