Grape Chemopreventive Agents Against Angiogenesis and Metastasis

Singh, Chandra K.; Chhabra, Gagan; Mintie, Charlotte A.; Ahmad, Nihal

doi:10.1007/978-3-030-39855-2_12

Cited by 6 publications

(7 citation statements)

References 109 publications

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“…We validated the expression of VEGF by immunoblotting to see the response of quercetin and resveratrol against PCa, and noticed a marked decrease especially in resveratrol and quercetin–resveratrol groups ( Figure 6 c). Vascular endothelial growth factor (VEGF) is a proangiogenic factor and a popular target to suppress angiogenesis by inhibiting its production [ 45 ]. Interestingly, VEGF is upregulated by epidermal growth factor receptor (EGFR), while on the other hand, VEGF upregulation independent of EGFR signaling contributes to resistance to EGFR inhibition [ 46 ].…”

Section: Resultsmentioning

confidence: 99%

“…EGFR overexpression is also observed frequently in circulating tumor cells (CTC) during PCa metastasis [ 47 ]. Expressions of VEGF and EGFR correlate with the metastatic characteristics, and therefore the inhibition of both has been shown to exert additive antitumor effects [ 45 , 46 ]. Our PCR array and its validation data ( Figure 4 a,b) clearly show a significant decrease in EGFR in all three treatment groups, suggesting the inhibitory role of quercetin and resveratrol against both, VEGF and EGFR signaling.…”

Section: Resultsmentioning

confidence: 99%

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Quercetin–Resveratrol Combination for Prostate Cancer Management in TRAMP Mice

Singh

Chhabra

Ndiaye

et al. 2020

Cancers

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Prostate Cancer (PCa) is a leading cause of cancer-related morbidity and mortality in men. Therefore, novel mechanistically-driven approaches are needed for PCa management. Here, we determined the effects of grape antioxidants quercetin and/or resveratrol (60 and 600 mg/kg, respectively, in diet) against PCa in Transgenic Adenocarcinoma of Mouse Prostate (TRAMP)-model in prevention and intervention settings. We found resveratrol alone and in combination significantly inhibited prostate tumorigenesis in prevention setting, while the same was seen only in combination after intervention. The observed effects were associated with marked inhibition in proliferation, oxidative stress, and tumor survival markers, and induced apoptosis markers. Utilizing PCa PCR array analysis with prevention tumor tissues, we identified that quercetin–resveratrol modulates genes involved in promoter methylation, cell cycle, apoptosis, fatty acid metabolism, transcription factors, androgen response, PI3K/AKT and PTEN signaling. Ingenuity Pathway Analysis (IPA) identified IGF1 and BCL2 as central players in two gene networks. Functional annotation predicted increased apoptosis and inhibited cell viability/proliferation, hyperplasia, vasculogenesis, and angiogenesis with dual treatment. Furthermore, IPA predicted upstream inhibition of major PCa signaling VEGF, Ca2+, PI3K, CSF2, PTH). Based on PCR array, we identified decreased levels of EGFR, EGR3, and IL6, and increased levels of IGFBP7 and NKX3.1, overall supporting anti-PCa effects of quercetin–resveratrol.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Quercetin–Resveratrol Combination for Prostate Cancer Management in TRAMP Mice

Singh

Chhabra

Ndiaye

et al. 2020

Cancers

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“…Cutaneous inflammation, as well as angiogenesis and metastasis within tumors, have been implicated as key players in promotion and progression of NMSCs [ 16 , 35 ]. Interestingly, several grape chemopreventive agents are known to affect multiple signaling molecules related to tumor angiogenesis and metastasis [ 36 ]. Previously, employing tandem mass tagging LC–MS/MS in tumor samples from our female model of UVB-induced carcinogenesis, we demonstrated that GP attenuates the chronic pro-inflammatory environment in skin tumors [ 37 ].…”

Section: Resultsmentioning

confidence: 99%

Protective Effects of Dietary Grape on UVB-Mediated Cutaneous Damages and Skin Tumorigenesis in SKH-1 Mice

Mintie

Musarra

Singh

et al. 2020

Cancers

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Non-melanoma skin cancers (NMSCs) are the most diagnosed cancers in the US and occur more frequently in males. We previously demonstrated chemoprotective effects of dietary grape powder (GP) against UVB-mediated skin tumorigenesis in female SKH-1 mice. To expand on this, here, we determined the effects of GP in a short-term UVB exposure protocol (0 or 5% GP, followed by UVB every other day for 2 weeks) in male and female SKH-1 mice, as well as explored any sex-related differences in UVB carcinogenesis via male SKH-1 mice (0, 3, or 5% GP; UVB twice weekly for 28 weeks). In the short-term study, we found that GP protects against early-stage epithelial hyperplasia and mast cell infiltration in both sexes. In the long term, GP markedly reduced tumor counts and malignant conversion, along with significant decreases in mast cell infiltration, serum IgE and Eotaxin. We also found inhibition of P38 phosphorylation and reduced PCNA, Ki67 and BCL2 levels, suggesting that the anti-inflammatory effects of GP inhibits P38, acting as an upstream regulator to inhibit proliferation and reduce tumor cell survival. Together, GP appears to protect against UVB-mediated skin damage and carcinogenesis in SKH-1 mice and should be explored further as a supplement for NMSC prevention.

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“…Studies show that antioxidants found in grapes may alleviate many health conditions including cancers [96][97][98]. Resveratrol's effects against cancers including its ability to inhibit key signaling events associated with tumor development and progression, and multidrug resistance, make it is a unique natural agent in cancer management [99,100]. Recent studies on resveratrol alone or combination were shown to have promising anticancer effects against PCa [101][102][103].…”

Section: Resveratrolmentioning

confidence: 99%

Dietary Phytochemicals in Zinc Homeostasis: A Strategy for Prostate Cancer Management

et al. 2021

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Studies have suggested an important role of the trace element zinc (Zn) in prostate biology and functions. Zn has been shown to exist in very high concentrations in the healthy prostate and is important for several prostatic functions. In prostate cancer (PCa), Zn levels are significantly decreased and inversely correlated with disease progression. Ideally, restoration of adequate Zn levels in premalignant/malignant prostate cells could abort prostate malignancy. However, studies have shown that Zn supplementation is not an efficient way to significantly increase Zn concentrations in PCa. Based on a limited number of investigations, the reason for the lower levels of Zn in PCa is believed to be the dysregulation of Zn transporters (especially ZIP and ZnT family of proteins), metallothioneins (for storing and releasing Zn), and their regulators (e.g., Zn finger transcription factor RREB1). Interestingly, the level of Zn in cells has been shown to be modulated by naturally occurring dietary phytochemicals. In this review, we discussed the effect of selected phytochemicals (quercetin, resveratrol, epigallocatechin-3-gallate and curcumin) on Zn functioning and proposes that Zn in combination with specific dietary phytochemicals may lead to enhanced Zn bioaccumulation in the prostate, and therefore, may inhibit PCa.

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Grape Chemopreventive Agents Against Angiogenesis and Metastasis

Cited by 6 publications

References 109 publications

Quercetin–Resveratrol Combination for Prostate Cancer Management in TRAMP Mice

Quercetin–Resveratrol Combination for Prostate Cancer Management in TRAMP Mice

Protective Effects of Dietary Grape on UVB-Mediated Cutaneous Damages and Skin Tumorigenesis in SKH-1 Mice

Dietary Phytochemicals in Zinc Homeostasis: A Strategy for Prostate Cancer Management

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