The Effects of Resveratrol on Prostate Cancer through Targeting the Tumor Microenvironment

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.

Improving the Antitumor Effect of Chemotherapy with Ocoxin as a Novel Adjuvant Agent to Treat Prostate Cancer

“…Along with that, recent studies discuss the effect of natural compounds, not only in prostate-cancer cells but and also in CAFs and osteoblasts. For instance, Pietrovito et al, discovered that cannabinoids act on cancer cells and CAFs at the same time by inhibiting CAF activation [38]; Silk and her colleagues reported that resveratrol downregulates Transforming Growth Factor β (TGFβ) expression while it exerts an antiproliferative and a pro-apoptotic effect in prostate CAFs [37]; and Ma and her collaborators found out that a Chinese natural medicine is able to cause CAF death and to reduce their pro-angiogenic capacity by reducing Vascular Endothelial Growth Factor A (VEGFA) production [39,93]. However, we could not detect any alteration regarding the presence of CAFs and TAMs in vivo due to the small number of infiltrated cells in the tumor stroma.…”

“…Indeed, many of those antitumor effects derive from TME modulation. For instance, resveratrol inhibits CAF differentiation, interrupts communication between tumor cells and TME and reduces TAM polarization to proinflammatory macrophages [37]. Likewise, cannabinoids impair CAF activation [38] and a compound containing Chinese herbs named Ligustilide induces their apoptosis and, therefore, reduces angiogenesis [39].…”

Identification of biomarkers for immunotherapy response in prostate cancer and potential drugs to alleviate immunosuppression

“…Previous studies revealed that resveratrol can reverse multidrug resistance in cancer cells, and when used in combination with clinically used drugs, it can sensitize cancer cells to standard chemotherapeutic agents [27]. There have been many reports that resveratrol can inhibit tumor processes by regulating multiple pathways, and the pathways affected by resveratrol, such as the PI3K pathway, Wnt signaling, and inflammation-related pathways, affect the PRCA immunosuppressive microenvironment [28]; thus, resveratrol could become an adjuvant drug for immunotherapy to help improve its effectiveness. I-BET-762 is also well studied and was reported to reduce MYC expression in PRCA and subsequently inhibit cell growth and reduce the tumor burden [29].…”

HS‑1793 inhibits cell proliferation in lung cancer by interfering with the interaction between p53 and MDM2

“…Resveratrol has demonstrated potential anti-cancer activity against several types of human cancer, including prostate ( 27 , 28 ), breast ( 29 , 30 ), colorectal ( 31 , 32 ), and skin cancers ( 33 ), and has also been used as a chemotherapeutic drug to treat various lung cancer cells ( 34 – 36 ). Its anti-lung cancer effect has been widely studied, with results suggesting that it could exert potent anti-tumor effects by upregulating microtubule-associated protein 1 light chain 3 ( 37 ) and p53 ( 38 ), downregulating smad activator 2 and 4 ( 39 ), and inhibiting the phosphatidylinositol-3-kinase pathway ( 40 ).…”