Phytochemicals Resveratrol and Sulforaphane as Potential Agents for Enhancing the Anti-Tumor Activities of Conventional Cancer Therapies

Kaminski, Bettina M.; Steinhilber, Dieter; Stein, Jürgen M.; Ulrich, S.

doi:10.2174/138920112798868746

Cited by 36 publications

(28 citation statements)

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“…This finding was substantiated by our observations that plasmid or lentiviral vector-mediated expression of 3'UTR-less c-MYC cDNA and chemotherapeutic drug cisplatin- or doxorubicin-induced endogenous c-MYC accumulation was also suppressed by either SFN or miR-214. SFN acts as a potent chemopreventive agent against cancer through modulating multiple signaling pathways involved in cell growth, apoptosis, inflammation and self-renewal of CSCs [4, 5, 38, 39]. Our study provides key mechanistic insights into how sulforaphane inhibits c-MYC activity, thereby exerting its anti-cancer and CSC effects.…”

Section: Discussionmentioning

confidence: 94%

Sulforaphane inhibits cancer stem-like cell properties and cisplatin resistance through miR-214-mediated downregulation of c-MYC in non-small cell lung cancer

Xie

et al. 2017

Oncotarget

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We herein report that sulforaphane (SFN), a potent anti-cancer and well-tolerated dietary compound, inhibits cancer stem-like cell (CSC) properties and enhances therapeutic efficacy of cisplatin in human non-small cell lung cancer (NSCLC). SFN exerted these functions through upregulation of miR-214, which in turn targets the coding region of c-MYC. This finding was further corroborated by our observations that plasmid or lentiviral vector-mediated expression of 3'UTR-less c-MYC cDNA and cisplatin- or doxorubicin-induced endogenous c-MYC accumulation was similarly suppressed by either SFN or miR-214. Further, we showed that the reported inhibitory effects of SFN on β-catenin are also mediated by miR-214. SFN/miR-214 signaling inhibited CSC properties and enhanced the cytotoxicity of chemotherapeutic drugs in vitro. Experiments with nude mice carrying xenograft tumors showed that SFN sensitized NSCLC cells to cisplatin's efficacy, which is accompanied by inhibition of cisplatin-induced c-MYC accumulation in tumor tissues. Our results provided strong evidence and mechanisms to support consideration of SFN or synthetic derivatives as a therapeutic agent in combination with cisplatin for the treatment of patients with NSCLC and, potentially, other types of c-MYC-addicted tumors.

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Section: Discussionmentioning

confidence: 94%

Sulforaphane inhibits cancer stem-like cell properties and cisplatin resistance through miR-214-mediated downregulation of c-MYC in non-small cell lung cancer

Xie

et al. 2017

Oncotarget

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“…Other studies have shown RES may sensitize cells by blocking chemotherapy-induced NFκB activity (44). However, in our cancer cell lines, RES did not inhibit NFκB activity (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Resveratrol and P-glycoprotein Inhibitors Enhance the Anti-Skin Cancer Effects of Ursolic Acid

Junco

Mancha

Malik

et al. 2013

Molecular Cancer Research

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Ursolic acid (UA), present in apples, rosemary, and other sources, is known to inhibit tumor formation and tumor cell viability in multiple systems, including skin. However, various cancers are resistant to UA treatment. Herein, skin carcinoma cells (Ca3/7) as compared to skin papilloma cells (MT1/2) displayed more resistance to UA-induced cytotoxicity. Interestingly, Ca3/7 cells had elevated levels of P-glycoprotein (P-gp), an ATP-dependent efflux pump that mediates resistance to chemotherapy in pre-clinical and clinical settings, and not only accumulated less but also more rapidly expelled the P-gp substrate Rhodamine 123 (Rh123) indicating UA is transported by P-gp. To determine if P-gp inhibition can enhance UA-mediated cytotoxicity, cells were challenged with P-gp inhibitors verapamil (VRP) or cyclosporin A (CsA). Alternatively, cells were pre-treated with the natural compound resveratrol (RES), a known chemotherapy sensitizer. VRP and RES enhanced the effects of UA in both cell lines, while CsA only did so in Ca3/7 cells. Similarly, VRP inhibited Rh123 efflux in both lines, while CsA only inhibited Rh123 efflux in Ca3/7 cells. RES did not inhibit Rh123 efflux in either line, indicating the synergistic effects of RES and UA are not manifest by inhibition of P-gp-mediated efflux of UA. These results indicate that the anti-skin cancer effects of UA are enhanced with P-gp inhibitors. In addition, RES and UA interact synergistically, but not through inhibition of P-gp. Implications Resveratrol and/or p-glycoprotein inhibitors in combination with ursolic acid are an effective anti-skin cancer regimen.

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“…It has been extensively studied for its antioxidant, anti-aging and anti-inflammatory activities181920212223. In addition, in vivo and in vitro studies showed that RES possesses potential anti-tumor activity against several malignancies24252627. According to our previous study, RES potentiates the cytotoxic properties of DOX in MCF-7, HeLa and HepG2 cells via P-gp inhibition and downregulation of MDR1 gene28.…”

mentioning

confidence: 93%

Didox and resveratrol sensitize colorectal cancer cells to doxorubicin via activating apoptosis and ameliorating P-glycoprotein activity

Khaleel

Al‐Abd

Ali

et al. 2016

Sci Rep

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Doxorubicin (DOX) has limited efficacy in colorectal cancer due to multi-drug resistance. Resveratrol (RES) and didox (DID) are polyhydroxyphenols with potential chemosensitizing effects. Herein, we assessed the chemomodulatory effects of RES and DID to DOX in colorectal cancer cells. Equitoxic combination of DOX with RES and DID in HCT 116 reduced the IC50 of DOX from 0.96 ± 0.02 μM to 0.52 ± 0.05 μM and 0.4 ± 0.06 μM, respectively. Similarly, combination of DOX with RES and DID in HT-29 decreased the IC50’s of DOX from 0.88 ± 0.03 μM to 0.47 ± 0.02 μM and 0.29 ± 0.04 μM, respectively. The expressions of p53 and Bax genes were markedly elevated in HCT 116 cells after exposure to DOX/DID. In HT-29 cells, the expression of Bcl-XL gene was significantly decreased after exposure to DOX/DID. In addition, combination of DOX with RES significantly increased the expression of Bax gene in HCT 116 cells. RES treatment induced significant S-phase arrest in DOX-treated HCT 116 cells, while DID induced G2/M- and S-phase arrest in HCT 116 and HT-29, respectively. Both RES and DID significantly enhanced the intracellular entrapment of DOX due to blocking the efflux activity of p-glycoprotein pump. In conclusion, RES and DID sensitize colorectal cancer cells to DOX via facilitating apoptosis and enhancing intracellular entrapment of DOX.

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Phytochemicals Resveratrol and Sulforaphane as Potential Agents for Enhancing the Anti-Tumor Activities of Conventional Cancer Therapies

Cited by 36 publications

References 0 publications

Sulforaphane inhibits cancer stem-like cell properties and cisplatin resistance through miR-214-mediated downregulation of c-MYC in non-small cell lung cancer

Sulforaphane inhibits cancer stem-like cell properties and cisplatin resistance through miR-214-mediated downregulation of c-MYC in non-small cell lung cancer

Resveratrol and P-glycoprotein Inhibitors Enhance the Anti-Skin Cancer Effects of Ursolic Acid

Didox and resveratrol sensitize colorectal cancer cells to doxorubicin via activating apoptosis and ameliorating P-glycoprotein activity

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