Bioactive natural products for chemoprevention and treatment of castration-resistant prostate cancer

Abstract

Prostate cancer (PCa), a hormonally-driven cancer, ranks first in incidence and second in cancer related mortality in men in most Western industrialized countries. Androgen and androgen receptor (AR) are the dominant modulators of PCa growth. Over the last two decades multiple advancements in screening, treatment, surveillance and palliative care of PCa have significantly increased quality of life and survival following diagnosis. However, over 20% of patients initially diagnosed with PCa still develop an aggressive and treatment-refractory disease. Prevention or treatment for hormone-refractory PCa using bioactive compounds from marine sponges, mushrooms, and edible plants either as single agents or as adjuvants to existing therapy, has not been clinically successful. Major advancements have been made in the identification, testing and modification of the existing molecular structures of natural products. Additionally, conjugation of these compounds to novel matrices has enhanced their bio-availability; a big step towards bringing natural products to clinical trials. Natural products derived from edible plants (nutraceuticals), and common folk-medicines might offer advantages over synthetic compounds due to their broader range of targets, as compared to mostly single target synthetic anticancer compounds; e.g. kinase inhibitors. The use of synthetic inhibitors or antibodies that target a single aberrant molecule in cancer cells might be in part responsible for emergence of treatment refractory cancers. Nutraceuticals that target AR signaling (epigallocatechin gallate [EGCG], curcumin, and 5α-reductase inhibitors), AR synthesis (ericifolin, capsaicin and others) or AR degradation (betulinic acid, di-indolyl diamine, sulphoraphane, silibinin and others) are prime candidates for use as adjuvant or mono-therapies. Nutraceuticals target multiple pathophysiological mechanisms involved during cancer development and progression and thus have potential to simultaneously inhibit both prostate cancer growth and metastatic progression (e.g., inhibition of angiogenesis, epithelial-mesenchymal transition (EMT) and proliferation). Given their multi-targeting properties along with relatively lower systemic toxicity, these compounds offer significant therapeutic advantages for prevention and treatment of PCa. This review emphasizes the potential application of some of the well-researched natural compounds that target AR for prevention and therapy of PCa.

Deciphering the roles of FOXO1 in human neoplasms

“…Prostate cancer is one of the most common neoplasms among aging males . As of 2011, prostate cancer is the second most frequently diagnosed cancer and the sixth leading cause of cancer‐related deaths in males worldwide .…”

“…Prostate cancer is one of the most common neoplasms among aging males. 73 As of 2011, prostate cancer is the second most frequently diagnosed cancer and the sixth leading cause of cancer-related deaths in males worldwide. 74 Zhang's group discovered that methylseleninic acid (MSA) treatment leads to rapid expression of FOXO1 as well as an increase in FOXO1 transcriptional activity, while blocking FOXO1 by gene silencing abolishes the pro-apoptosis actions of prostate cancer, suggesting that FOXO1 plays a critical role in mediating the apoptotic effect of MSA.…”

Cranberry intervention in patients with prostate cancer prior to radical prostatectomy. Clinical, pathological and laboratory findings

“…4 ). Thus, food components (nutraceuticals) or complex plant extracts act as anti-oxidants, anti-inflammatory remedies, weak 5α-reductase inhibitors or target androgen receptor (AR) synthesis and signalling 5 . Molecular mechanisms of the anti-cancer action of natural products were mostly studied on human androgen-dependent and/or independent prostate cell lines.…”

Anticancer effect of SZC015 on pancreatic cancer via mitochondria‐dependent apoptosis and the constitutive suppression of activated nuclear factor κB and STAT3 in vitro and in vivo

“…apoptosis, mitochondria, NF-κB and STAT3, pancreatic cancer, SZC015 (Kallifatidis, Hoy, & Lokeshwar, 2016). As a widely abundant natural product, oleanolic acid (OA) has exerted a variety of pharmacological activities, especially anticancer function (Park et al, 2014;Pollier & Goossens, 2012;X.…”