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

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.

Dietary Manipulation for Therapeutic Effect in Prostate Cancer

“…In vivo combination therapy of soy isoflavones and radiation for prostate cancer has also been investigated, with favorable effects on the control of the disease (Raffoul et al, 2007;Wang et al, 2006). Docetaxel effect in castration-resistant prostate cancer patients was improved by lycopene via insulin-like growth factor 1 receptor perturbation (Tang et al, 2011). Using an animal model to confirm these findings, a 38% improvement over docetaxel was found (P=0.047).…”

“…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).…”

Investigation of the Potential Anticancer Effects of Lycopene in Tissue Engineered In vitro and In vivo Models

“…IGFBP2 is a binding protein for IGF-I, which has been shown to be highly expressed in LNCaP cells [59]. Another study conducted by Tang et al [75] revealed that lycopene induced a more distinct inhibitory effect on the growth of DU145 prostate cancer cells, which exhibit a greater expression profile of IGF-IR, than on LNCaP, 22Rv1 or PC3 cells, which have a less pronounced IGF-IR level. Though lycopene accumulation in LNCaP cells has been detected to be more than four times higher than in DU145 cells, the growth inhibitory effect has been shown to be seven times less distinct.…”

“…These predominantly colourful molecules, built by plants, fungi and bacteria undergoing photosynthesis, are widespread in vegetables and fruits [75,76]. Carotenoids are divided into two main groups.…”

“…Though plenty of clinical studies have been performed so far, only a few preclinical in vivo studies have been published (Table 3). In August 2011, Ilic et al identified 64 clinical studies [81], whereas at the same time, only 12 animal models had been published investigating the effects of lycopene on prostate cancer [75,[82][83][84][85][86][87][88][89][90].…”