ArticleChinese medicine2019
Combination of shikonin with paclitaxel overcomes multidrug resistance in human ovarian carcinoma cells in a P-gp-independent manner through enhanced ROS generation.
Article in Chinese medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 135 citations in OpenAlex.
- Empowering of novel anti-tumor formulations with quinone-based active natural products.Biomaterials translational · 2026Review
- Development and validation of a UPLC-MS/MS method for the quantification of asciminib and its pharmacokinetic interaction and metabolic stability with shikonin.BMC pharmacology & toxicology · 2025Article
- Targeting stem-property and vasculogenic mimicry for sensitizing paclitaxel therapy of triple-negative breast cancer by biomimetic codelivery.Acta pharmaceutica Sinica. B · 2025Article
- Synergistic Effect of Ribitol and Shikonin Promotes Apoptosis in Breast Cancer Cells.International journal of molecular sciences · 2025Article
- Therapeutic Chemoresistance in Ovarian Cancer: Emerging Hallmarks, Signaling Mechanisms and Alternative Pathways.Current medicinal chemistry · 2025Review
- Review projecting shikonin as a therapeutic candidate in female carcinomas: a preclinical perspective.Frontiers in pharmacology · 2025Review
- Formononetin Defeats Multidrug-Resistant Cancers by Induction of Oxidative Stress and Suppression of P-Glycoprotein.International journal of molecular sciences · 2024Article
- Identification of small molecular inhibitors of SIRT3 by computational and biochemical approaches a potential target of breast cancer.Scientific reports · 2024Article
- Shikonin reduces M2 macrophage population in ovarian cancer by repressing exosome production and the exosomal galectin 3-mediated β-catenin activation.Journal of ovarian research · 2024Article
- Research progress in mechanism of anticancer action of shikonin targeting reactive oxygen species.Frontiers in pharmacology · 2024Review
- The photoactivated antifungal activity and possible mode of action of sodium pheophorbide a onFrontiers in microbiology · 2024Article
- Shikonin Causes an Apoptotic Effect on Human Kidney Cancer Cells through Ras/MAPK and PI3K/AKT Pathways.Molecules (Basel, Switzerland) · 2023Article
- The anti-leukemia activity and mechanisms of shikonin: a mini review.Frontiers in pharmacology · 2023Review
- Applying formative evaluation in the mentoring of student intern nurses in an emergency department.Frontiers in public health · 2022Article
- The Role of PKM2 in the Regulation of Mitochondrial Function: Focus on Mitochondrial Metabolism, Oxidative Stress, Dynamic, and Apoptosis. PKM2 in Mitochondrial Function.Oxidative medicine and cellular longevity · 2022Review
- Inhibition of PKM2 Enhances Sensitivity of Olaparib to Ovarian Cancer Cells and Induces DNA Damage.International journal of biological sciences · 2022Article
- Shikonin promotes ubiquitination and degradation of cIAP1/2-mediated apoptosis and necrosis in triple negative breast cancer cells.Chinese medicine · 2021Article
- Role of PKM2-Mediated Immunometabolic Reprogramming on Development of Cytokine Storm.Frontiers in immunology · 2021Review
- Comprehensive study of altered proteomic landscape in proximal renal tubular epithelial cells in response to calcium oxalate monohydrate crystals.BMC urology · 2020Article
- Shikonin and 4-hydroxytamoxifen synergistically inhibit the proliferation of breast cancer cells through activating apoptosis signaling pathway in vitro and in vivo.Chinese medicine · 2020Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundShikonin (SKN), a naphthoquinone compound, is isolated from Chinese herbal medicine
methodsHuman ovarian carcinoma A2780 cell along with the paired PTX-resistant A2780/PTX cells were used. The effects of SKN, PTX or their combination on cell viability were conducted using Sulforhodamine B assay. P-glycoprotein (P-gp) expression was analyzed by flow cytometry after staining with P-gp-FITC anti-body. P-gp activity was determined by a fluorometric MDR assay kit or a rhodamine 123-based efflux assay, respectively. Apoptosis was evaluated by flow cytometry after Annexin V-FITC/PI co-staining. The effect of SKN, PTX or their combination on reactive oxygen species (ROS) generation and expression of pyruvate kinase M2 (PKM2) were investigated using flow cytometry or western blotting, respectively. PKM2 activity was detected by a Pyruvate Kinase Assay Kit.
resultsSKN/PTX co-treatment led to synergistically enhanced cytotoxicity and apoptosis in PTX-resistant ovarian cancer cells, indicating the circumvention of multidrug resistance (MDR) of PTX by SKN. Further study indicated that the MDR reversal effect of SKN was independent of inhibiting activity of the efflux transporter P-gp. Notably, SKN/PTX significantly increased the generation of intracellular ROS in A2780/PTX cells, and scavenging intracellular ROS blocked the sensitizing effects of SKN in PTX-induced cytotoxicity and apoptosis in A2780/PTX cells, but not in A2780 cells. Furthermore, SKN/PTX-induced downregulation of PKM2 (a key enzyme in glycolysis) and the suppression of its activity were inhibited by a ROS scavenger N-acetyl cysteine (NAC), suggesting that the synergy of the SKN/PTX combination may be not rely on PKM2 suppression.
conclusionsThese results reveal a P-gp-independent mechanism through ROS generation for the SKN/PTX combination to overcome MDR in ovarian cancer.
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