ArticleMolecular cancer research : MCR2013
Resveratrol and P-glycoprotein inhibitors enhance the anti-skin cancer effects of ursolic acid.
Article in Molecular cancer research : MCR, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 3 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 3 syntheses or guidelines pooled it, 32 citations in OpenAlex.
- Natural Compounds for the Treatment of Cutaneous Squamous Cell Carcinoma: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- The bioactivities of resveratrol and its naturally occurring derivatives on skin.Journal of food and drug analysis · 2021Pooled it
- A Systematic Review of the Potential Chemoprotective Effects of Resveratrol on Doxorubicin-Induced Cardiotoxicity: Focus on the Antioxidant, Antiapoptotic, and Anti-Inflammatory Activities.Oxidative medicine and cellular longevity · 2021Pooled it
- From Nature to Nanomedicine: Enhancing the Antitumor Efficacy of Rhein, Curcumin, and Resveratrol.Medicina (Kaunas, Lithuania) · 2025Review
- Resveratrol in the Treatment of Gynecological Cancer: Mechanisms and Therapeutic Potential.Current medicinal chemistry · 2025Review
- Effects of Resveratrol on Nonmelanoma Skin Cancer (NMSC): A Comprehensive Review.Food science & nutrition · 2024Review
- Natural Compounds in Non-Melanoma Skin Cancer: Prevention and Treatment.Molecules (Basel, Switzerland) · 2024Review
- A systematic review of the therapeutic effects of resveratrol in combination with 5-fluorouracil during colorectal cancer treatment: with a special focus on the oxidant, apoptotic, and anti-inflammatory activities.Cancer cell international · 2022Review
- Nano-Resveratrol: A Promising Candidate for the Treatment of Renal Toxicity Induced by Doxorubicin in Rats Through Modulation of Beclin-1 and mTOR.Frontiers in pharmacology · 2022Article
- The Therapeutic Potential of Common Herbal and Nano-Based Herbal Formulations against Ovarian Cancer: New Insight into the Current Evidence.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Reduction of breast tumor drug resistance by 2,3,5,4'-tetrahydroxystilbene for exhibition synergic chemotherapeutic effect.PloS one · 2021Article
- The Analysis of the Anti-Tumor Mechanism of Ursolic Acid Using Connectively Map Approach in Breast Cancer Cells Line MCF-7.Cancer management and research · 2020Article
- Effect of resveratrol on drug resistance in colon cancer chemotherapy.RSC advances · 2019Article
- Role of AMPK and PPARα in the anti-skin cancer effects of ursolic acid.Molecular carcinogenesis · 2018Article
- Chronic morphine exposure potentiates p-glycoprotein trafficking from nuclear reservoirs in cortical rat brain microvessels.PloS one · 2018Article
- Use of Polyphenolic Compounds in Dermatologic Oncology.American journal of clinical dermatology · 2016Review
- CIP2A is associated with multidrug resistance in cervical adenocarcinoma by a P-glycoprotein pathway.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Effect of Combined Treatment with Ursolic Acid and Resveratrol on Skin Tumor Promotion by 12-O-Tetradecanoylphorbol-13-Acetate.Cancer prevention research (Philadelphia, Pa.) · 2015Article
- By reducing hexokinase 2, resveratrol induces apoptosis in HCC cells addicted to aerobic glycolysis and inhibits tumor growth in mice.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledUrsolic acid, 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 ursolic acid treatment. Herein, skin carcinoma cells (Ca3/7) as compared with skin papilloma cells (MT1/2) displayed more resistance to ursolic acid-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 preclinical and clinical settings, and not only accumulated less but also more rapidly expelled the P-gp substrate rhodamine 123 (Rh123) indicating ursolic acid is transported by P-gp. To determine whether P-gp inhibition can enhance ursolic acid-mediated cytotoxicity, cells were challenged with P-gp inhibitors verapamil or cyclosporin A. Alternatively, cells were pretreated with the natural compound resveratrol, a known chemotherapy sensitizer. Verapamil and resveratrol enhanced the effects of ursolic acid in both cell lines, whereas cyclosporin A only did so in Ca3/7 cells. Similarly, verapamil inhibited Rh123 efflux in both lines, whereas cyclosporin A only inhibited Rh123 efflux in Ca3/7 cells. Resveratrol did not inhibit Rh123 efflux in either line, indicating the synergistic effects of resveratrol and ursolic acid are not manifest by inhibition of P-gp-mediated efflux of ursolic acid. These results indicate that the anti-skin cancer effects of ursolic acid are enhanced with P-gp inhibitors. In addition, resveratrol and ursolic acid 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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Registered trials
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