Abstract
Prostate cancer is one of the most common cancers diagnosed in men in the United States and the second leading cause of cancer-related deaths worldwide. Since over 60% of prostate cancer cases occur in men over 65 years of age, and this population will increase steadily in the coming years, prostate cancer will be a major cancer-related burden in the foreseeable future. Accumulating data from more recent research suggest that the tumor microenvironment (TME) plays a previously unrecognized role in every stage of cancer development, including initiation, proliferation, and metastasis. Prostate cancer is not only diagnosed in the late stages of life, but also progresses relatively slowly. This makes prostate cancer an ideal model system for exploring the potential of natural products as cancer prevention and/or treatment reagents because they usually act relatively slowly compared to most synthetic drugs. Resveratrol (RSV) is a naturally occurring stilbenoid and possesses strong anti-cancer properties with few adverse effects. Accumulating data from both in vitro and in vivo experiments indicate that RSV can interfere with prostate cancer initiation and progression by targeting the TME. Therefore, this review is aimed to summarize the recent advancement in RSV-inhibited prostate cancer initiation, proliferation, and metastasis as well as the underlying molecular mechanisms, with particular emphasis on the effect of RSV on TME. This will not only better our understanding of prostate cancer TMEs, but also pave the way for the development of RSV as a potential reagent for prostate cancer prevention and/or therapy.
Highlights
Prostate cancer is the second most common cancer in the world, resulting in over 350,000 deaths in 2018 [1]
These findings altogether indicate that the stromal cells play an important role in prostate cancer initiation, and malignant cells are capable of affecting stromal cell behavior
Vancauwenberghe et al [26] further demonstrated that by inhibiting the transient receptor potential ankyrin 1 (TRPA1), RSV is capable of blocking the secretion of both HGF and vascular endothelial growth factor (VEGF), an important factor involving the angiogenesis of tumor tissues
Summary
Prostate cancer is the second most common cancer in the world, resulting in over 350,000 deaths in 2018 [1]. Because of the importance of the androgen/androgen receptor (AR) signaling pathway in prostate cancer initiation and progression [5], most basic and clinical research has been focused on the androgen/AR axis. Multiple lines of evidence from recent research indicate that, in addition to the androgen/AR axis, the tumor microenvironment (TME) plays an indispensable role in prostate cancer initiation and progression [9,10]. Accumulating data demonstrate that resveratrol (RSV), a stilbenoid produced in multiple plants, possesses strong anti-cancer properties [22,23] By targeting both AR [24] and the TME [25,26], RSV can induce growth inhibition, cell cycle arrest, apoptosis, as well as inhibit metastasis of different cancer types, including prostate cancer [22,27]. To pave the road for the development of RSV as a preventive and/or therapeutic reagent, either by itself or in combination with other drugs, our review focuses on the effects of RSV on the TME in prostate cancer initiation, proliferation, and metastasis
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