Molecular Basis of Prostate Cancer and Natural Products as Potential Chemotherapeutic and Chemopreventive Agents

Abstract

Prostate cancer is the second most common malignant cancer in males. It involves a complex process driven by diverse molecular pathways that closely related to the survival, apoptosis, metabolic and metastatic characteristics of aggressive cancer. Prostate cancer can be categorized into androgen dependent prostate cancer and castration-resistant prostate cancer and cure remains elusive due to the developed resistance of the disease. Natural compounds represent an extraordinary resource of structural scaffolds with high diversity that can offer promising chemical agents for making prostate cancer less devastating and curable. Herein, those natural compounds of different origins and structures with potential cytotoxicity and/or in vivo anti-tumor activities against prostate cancer are critically reviewed and summarized according to the cellular signaling pathways they interfere. Moreover, the anti-prostate cancer efficacy of many nutrients, medicinal plant extracts and Chinese medical formulations were presented, and the future prospects for the application of these compounds and extracts were discussed. Although the failure of conventional chemotherapy as well as involved serious side effects makes natural products ideal candidates for the treatment of prostate cancer, more investigations of preclinical and even clinical studies are necessary to make use of these medical substances reasonably. Therefore, the elucidation of structure-activity relationship and precise mechanism of action, identification of novel potential molecular targets, and optimization of drug combination are essential in natural medicine research and development.

Computer-aided analysis of quercetin mechanism of overcoming docetaxel resistance in docetaxel-resistant prostate cancer

“…Further analysis of the PPI network revealed EGFR as the topmost gene that interacted with other proteins present in the network. The alterations of the components of certain pathways including the PI3K/Akt pathway have been reported in most metastatic PC [ 39 ]. Consequently, the levels and types of alterations of the hub genes in PC patients were examined.…”

Co‐targeting SKP2 and KDM5B inhibits prostate cancer progression by abrogating AKT signaling with induction of senescence and apoptosis

“…2 Although androgen deprivation therapy (ADT) is the first-line treatment to primary PCa, relapse is often observed in most PCa patients who ultimately develop castration-resistant prostate cancer (CRPC). Development and progression of CRPC are an intricate process involving the alterations of many molecular pathways, 3 of which a major component is the PI3K/AKT signaling pathway. 4,5 Although there are therapies in clinical trials to treat CRPC (e.g., docetaxel and enzalutamide), resistance to these therapies occurs in most patients, which may lead to malignant progression.…”

Targeting PHB1 to inhibit castration-resistant prostate cancer progression in vitro and in vivo

“…The aberrant activation of AR signaling plays a vital role in PCa progression and androgen deprivation therapy (ADT) is the primary therapy for locally advanced or metastatic PCa, but most patients will gradually develop from androgen-dependent prostate cancer (ADPC) into castration-resistant prostate cancer (CRPC) after initial treatment [ 2 ]. The occurrence and development of CRPC is a complex process involved and driven by multiple molecular pathways [ 3 ], in which reactivation of the AR signal pathway is a critical driver of CRPC. Although AR-targeted drugs such as Enzalutamide (ENZ) as well as drugs targeting other CRPC-driver genes, such as AKT inhibitor ipatasertib, PARP inhibitors olaparib and rucaparib, have improved the clinical outcome of CRPC patients, disease resistance remains a serious challenge [ 3 – 6 7 ].…”