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.

1
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

2
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

3
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

4
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 16-18 months
• Myelosuppresion, Neurotoxicity, and fatigue
• Can it be combined to improve its use?

5
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?

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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

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Results
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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

9
Questions