The In Vitro Anti-Tumor Activity of Docetaxel in Combination with Inositol Hexaphosphate (IP-6) in Castrate-Resistant PC3 and DU-145 Prostate Cancer Cell Lines. Adam M Luchey md Division of Urology, Department of Surgery West Virginia University Dale Riggs, Barbara Jackson, Can Talug, Stanley Kandzari, Dana Point, and Stanley Zaslau

Prostate Cancer Prostate cancer is the most common internal tumor in US males and second leading cause of cancer death Initial treatments are surgery (open, laparoscopic, robotic), brachytherapy & external beam radiation Further treatment is based on PSA (Prostate Specific Antigen) If elevated (biochemical recurrence), treatment is either radiation or hormonal therapy

Androgen Deprivation Lutenizing Hormone Releasing Hormone (LHRH) agonists Leads to decrease in FSH and LH Leuprolide, Gosrelin Androgen Synthesis Inhibitors Ketoconazole Aminoglutethimide Nonsteroidal Antiandrogens Libido and Potency preserved Steroidal Antiandrogens Surgery

Castrate-Resistant Prostate Cancer Formally known as Hormone-Resistant Prostate Cancer On average occurs in 2 years Add additional agents Antiandrogen Surgical castration Chemotherapy Docetaxel regimen Only prolongs survival months Myelosuppresion, Neurotoxicity, and fatigue Can it be combined to improve its use?

IP-6 Inositol-Hexaphosphate is a polyphosphorylated carbohydrate found in legumes and cereals that are high in fiber Shown to disrupt the growth of (in vivo and in vitro) numerous cancer lines (breast, pancrease, prostate, melanoma) We have previously shown its inhibitory effect through induction of apoptosis/necrosis and as an inhibitor of VEGF and GI bladder cancer cell lines Can this be combined with docetaxel to improve its effect and limit its side effects?

Project Design PC3 and DU-145 Castrate-Resistant Prostate Cancer Cell Lines Both were cultured with IP-6 (0.25 and 0.5 mM/well) and/or Docetaxel (2.5 and 5 nM/well) Cell Viability determined at 24, 48, and 72 hours using MTT assay Statistical analysis preformed via ANOVA and individual comparisons by the Tukey Test

Results

Conclusions When combined, Docetaxel and IP-6 have an additive effect causing increase in cell kill With IP-6, a dose of 2.5 nM of Docetaxel had more of an effect than a dose of 5.0 nM More effective and less toxic Need to further delineate IP-6 action Necrosis/Apoptosis Cell cycle inhibition In vitro to in vivo studies

Questions