Resveratrol for cancer therapy: Challenges and future perspectives

Ren, Boxu; Kwah, Marabeth Xin-Yi; Liu, Cuiliu; Ma, Zhaowu; Shanmugam, Muthu K.; Ding, Ling-Wen; Xiang, Xiaoqiang; Ho, Paul C.; Wang, Lingzhi; Ong, Pei Shi; Goh, Boon Cher

doi:10.1016/j.canlet.2021.05.001

Cited by 224 publications

(133 citation statements)

References 89 publications

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“…Some of them, such as resveratrol and pterostilbene, have been ascribed to a wide range of biological activities against cancer. Most notable of them are associated with effects on oxidative homeostasis, membrane structure and integrity, as well as a broad scope of intracellular pathways, ultimately activating responses resulting in tumor cell inhibition and chemosensitization—these activities are summarized in the recent excellent reviews ( Obrador et al, 2021 ; Quarta et al, 2021 ; Ren et al, 2021 ). It has been further reported that resveratrol and pterostilbene have a potential Wnt-inhibition activity in several models and tissues ( Blagodatski et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Chemoenzymatic Synthesis of Original Stilbene Dimers Possessing Wnt Inhibition Activity in Triple-Negative Breast Cancer Cells Using the Enzymatic Secretome of Botrytis cinerea Pers.

et al. 2022

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The Wnt signaling pathway controls multiple events during embryonic development of multicellular animals and is carcinogenic when aberrantly activated in adults. Breast cancer and triple-negative breast cancer (TNBC) in particular depend upon Wnt pathway overactivation. Despite this importance, no Wnt pathway-targeting drugs are currently available, which necessitates novel approaches to search for therapeutically relevant compounds targeting this oncogenic pathway. Stilbene analogs represent an under-explored field of therapeutic natural products research. In the present work, a library of complex stilbene derivatives was obtained through biotransformation of a mixture of resveratrol and pterostilbene using the enzymatic secretome of Botrytis cinerea. To improve the chemodiversity, the reactions were performed using i-PrOH, n-BuOH, i-BuOH, EtOH, or MeOH as cosolvents. Using this strategy, a series of 73 unusual derivatives was generated distributed among 6 scaffolds; 55 derivatives represent novel compounds. The structure of each compound isolated was determined by nuclear magnetic resonance and high-resolution mass spectrometry. The inhibitory activity of the isolated compounds against the oncogenic Wnt pathway was comprehensively quantified and correlated with their capacity to inhibit the growth of the cancer cells, leading to insights into structure-activity relationships of the derivatives. Finally, we have dissected mechanistic details of the stilbene derivatives activity within the pathway.

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Section: Introductionmentioning

confidence: 99%

Chemoenzymatic Synthesis of Original Stilbene Dimers Possessing Wnt Inhibition Activity in Triple-Negative Breast Cancer Cells Using the Enzymatic Secretome of Botrytis cinerea Pers.

et al. 2022

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“…Furthermore, initial PT2385 administration to a patient suffering metastatic renal carcinoma (ccRCC), followed by a Phase I clinical trial in patients with advanced ccRCC, PT2385 showed promising efficacy and tolerability as monotherapy [ 220 , 221 ]. Consistently, a recent meta-analysis of nine previous studies showed an inverse correlation between circulating and dietary vitamin D levels and the occurrence of ccRCC [ 222 ], suggesting that a combination of HIF inhibitors (including natural compounds such as flavonoids, celastrol, and resveratrol [ 223 , 224 , 225 ]) and calcitriol could be a potential anticancer strategy to treat ccRCC.…”

Section: Cancer–hypoxia–vitamin Dmentioning

confidence: 60%

Vitamin D and Hypoxia: Points of Interplay in Cancer

Gkotinakou

Mylonis

Tsakalof

2022

Cancers

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Vitamin D is a hormone that, through its action, elicits a broad spectrum of physiological responses ranging from classic to nonclassical actions such as bone morphogenesis and immune function. In parallel, many studies describe the antiproliferative, proapoptotic, antiangiogenic effects of calcitriol (the active hormonal form) that contribute to its anticancer activity. Additionally, epidemiological data signify the inverse correlation between vitamin D levels and cancer risk. On the contrary, tumors possess several adaptive mechanisms that enable them to evade the anticancer effects of calcitriol. Such maladaptive processes are often a characteristic of the cancer microenvironment, which in solid tumors is frequently hypoxic and elicits the overexpression of Hypoxia-Inducible Factors (HIFs). HIF-mediated signaling not only contributes to cancer cell survival and proliferation but also confers resistance to anticancer agents. Taking into consideration that calcitriol intertwines with signaling events elicited by the hypoxic status cells, this review examines their interplay in cellular signaling to give the opportunity to better understand their relationship in cancer development and their prospect for the treatment of cancer.

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“…The effect of resveratrol was only evaluated in vitro . However, resveratrol has shown remarkable efficacy for cancer treatment in vivo ( 39 ). Moreover, resveratrol acts as a chemopreventive agent in the four major stages of carcinogenesis, namely, initiation, promotion, progression, and metastasis ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

Resveratrol affects the migration and apoptosis of monocytes by blocking HMGB1/NF-κB pathway

Zhang¹,

Dong²,

Liu³

et al. 2021

Transl Cancer Res TCR

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Background: Chronic inflammation is now recognized as a causal factor of aging. Resveratrol is a nonflavonoid compound that widely exists in plant species, exerting anti-inflammatory effects in vitro and in animal models. The chemotaxis of inflammatory cells and secretion of cytokines are key characters in inflammation response.Methods: The effects of lipopolysaccharide (LPS) and high mobility group box-1 (HMGB1) chromosomal on the migration, inflammatory response, and apoptosis of monocytes were detected. THP-1 cells were used to study the effects of resveratrol treatment on LPS-and HMGB-induced monocytes. We aimed to investigate the effect of Resveratrol on monocyte migration and the expression of a special cytokine named HMGB1 in THP-1 cells.Results: Resveratrol obviously inhibited THP-1 migration induced by LPS. LPS increased the expression of HMGB1 and its release in THP-1 cells, which were both decreased by resveratrol. Resveratrol inhibited the activity of NF-κB-p65 and the translocation of NF-κB-p65 from nucleus to cytoplasm induced by LPS.In addition, Resveratrol increased LPS and HMGB1-inhibited monocyte apoptosis. Resveratrol inhibited the LPS-induced HMGB1 secretion and its activation through NF-κB pathway. The THP-1 migration induced by LPS was inhibited by resveratrol.Conclusions: Resveratrol may inhibit monocyte migration and induce apoptosis by blocking downstream HMGB1/NF-κB/MCP-1 signaling pathways, thereby reducing systemic inflammation.

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Resveratrol for cancer therapy: Challenges and future perspectives

Cited by 224 publications

References 89 publications

Chemoenzymatic Synthesis of Original Stilbene Dimers Possessing Wnt Inhibition Activity in Triple-Negative Breast Cancer Cells Using the Enzymatic Secretome of Botrytis cinerea Pers.

Chemoenzymatic Synthesis of Original Stilbene Dimers Possessing Wnt Inhibition Activity in Triple-Negative Breast Cancer Cells Using the Enzymatic Secretome of Botrytis cinerea Pers.

Vitamin D and Hypoxia: Points of Interplay in Cancer

Resveratrol affects the migration and apoptosis of monocytes by blocking HMGB1/NF-κB pathway

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