Article

Lycopene Enhances Docetaxel's Effect in Castration-Resistant Prostate Cancer Associated with Insulin-like Growth Factor I Receptor Levels 1

Department of Urology, University of California, Irvine, Orange, CA, USA.
Neoplasia (New York, N.Y.) (Impact Factor: 5.4). 02/2011; 13(2):108-19. DOI: 10.1593/neo.101092
Source: PubMed

ABSTRACT Docetaxel is currently the most effective drug for the treatment of castration-resistant prostate cancer (CRPC), but it only extends life by an average of 2 months. Lycopene, an antioxidant phytochemical, has antitumor activity against prostate cancer (PCa) in several models and is generally safe. We present data on the interaction between docetaxel and lycopene in CRPC models. The growth-inhibitory effect of lycopene on PCa cell lines was positively associated with insulin-like growth factor I receptor (IGF-IR) levels. In addition, lycopene treatment enhanced the growth-inhibitory effect of docetaxel more effectively on DU145 cells with IGF-IR high expression than on those PCa cell lines with IGF-IR low expression. In a DU145 xenograft tumor model, docetaxel plus lycopene caused tumor regression, with a 38% increase in antitumor efficacy (P = .047) when compared with docetaxel alone. Lycopene inhibited IGF-IR activation through inhibiting IGF-I stimulation and by increasing the expression and secretion of IGF-BP3. Downstream effects include inhibition of AKT kinase activity and survivin expression, followed by apoptosis. Together, the enhancement of docetaxel's antitumor efficacy by lycopene supplementation justifies further clinical investigation of lycopene and docetaxel combination for CRPC patients. CRPC patients with IGF-IR-overexpressing tumors may be most likely to benefit from this combination.

Download full-text

Full-text

Available from: John P Fruehauf, Aug 24, 2015
0 Followers
 · 
185 Views
  • Source
    • "Moreover, tomato supplemented diet in patients with coronary heart disease has been shown to significantly improve the levels of serum enzymes involved in antioxidant activities and decreased lipid peroxidation rate (Bose and Agrawal, 2007). Lycopene has recently been shown to enhance docetaxel's effect in castration-resistant prostate cancer associated with insulin-like growth factor 1 receptor (Tang et al., 2011). Since castration increases oxidative stress due to testosterone deficiency, study on the likely effects of tomatoes in ameliorating the castration-induced oxidative stress was of interest. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Castration has previously been shown to induce oxidative stress. Previous studies have shown tomato to be a potent anti-oxidant which reduces oxidative stress in many disease conditions. However, the likely role of tomato in ameliorating castration-induced oxidative stress has not been studied and was of interest to us. The present study looked into the effect of tomato supplement on the plasma level of antioxidant enzymes like superoxide dismutase (SOD) and catalase, level of lipid peroxidation rate by estimating the malondialdehyde (MDA) and other parameters like weight gain and blood glucose levels in castrated and sham-operated rats. Castration did not affect weight gain and plasma catalase level; but increased plasma glucose and MDA levels and decreased plasma SOD level. Tomato supple-mentation reduced weight gain but had no effect on castration-induced hyperglycemia. It also increased plasma SOD and catalase, and decreased plasma MDA level in the castrated rats. These findings suggested that tomato supplementation might have important therapeutic potential as an anti-oxidant during castration and a weight regulator in castrates and non-castrates.
  • Source
    • "Moreover, tomato supplemented diet in patients with coronary heart disease has been shown to significantly improve the levels of serum enzymes involved in antioxidant activities and decreased lipid peroxidation rate (Bose and Agrawal, 2007). Lycopene has recently been shown to enhance docetaxel's effect in castration-resistant prostate cancer associated with insulin-like growth factor 1 receptor (Tang et al., 2011). Since castration increases oxidative stress due to testosterone deficiency, study on the likely effects of tomatoes in ameliorating the castration-induced oxidative stress was of interest. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Castration has previously been shown to induce oxidative stress. Previous studies had shown tomato as a potent anti-oxidant which reduces oxidative stress in many disease conditions. However, the likely role of tomato to ameliorate castration-induced oxidative stress has not been studied and was of interest to us. The present study looked into the effect of tomato supplement on the plasma level of antioxidant enzymes like superoxide dismutase (SOD) and catalase, level of lipid peroxidation rate by estimating the Malondialdehyde (MDA) and other parameters like weight gain and blood glucose levels in castrated and sham-operated rats. Castration did not affect weight gain and plasma catalase level; increased plasma glucose and MDA levels and decrease plasma SOD level. Tomato supplementation reduced weight gain and had no effect on castration-induced hyperglycemia. It also increased plasma SOD and catalase, and decreased plasma MDA level in the castrated rats. These findings suggested that tomato supplementation might have important therapeutic potential as an anti-oxidant during castration and a weight regulator in castrates and non-castrates.
    10th annual scientific conference of the Anatomical Society of Nigeria (ASN); 11/2012
  • Source
    • "In combination with docetaxel, lycopene inhibits growth of hormone independent prostate cancer DU145 cells through insulin-like growth factor 1 receptors leading to downstream inhibition of survivin expression and subsequent apoptosis (Tang et al., 2011). "
    Cancer Prevention - From Mechanisms to Translational Benefits, 04/2012; , ISBN: 978-953-51-0547-3
Show more