ArticleScientific reports2018
Broad blocking of MDR efflux pumps by acetylshikonin and acetoxyisovalerylshikonin to generate hypersensitive phenotype of malignant carcinoma cells.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 35 citations in OpenAlex.
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- Acetylshikonin induces necroptosis via the RIPK1/RIPK3-dependent pathway in lung cancer.Aging · 2023Article
- Mechanism of multidrug resistance to chemotherapy mediated by P‑glycoprotein (Review).International journal of oncology · 2023Review
- Anticancer and chemosensitizing activities of stilbenoids from three orchid species.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Inventory of ATP-binding cassette proteins in Lithospermum erythrorhizon as a model plant producing divergent secondary metabolites.DNA research : an international journal for rapid publication of reports on genes and genomes · 2022Article
- Single-Cell Image-Based Analysis Reveals Chromatin Changes during the Acquisition of Tamoxifen Drug Resistance.Life (Basel, Switzerland) · 2022Article
- Targeting Drug Chemo-Resistance in Cancer Using Natural Products.Biomedicines · 2021Review
- Normalizing Tumor Vasculature to Reduce Hypoxia, Enhance Perfusion, and Optimize Therapy Uptake.Cancers · 2021Review
- Pharmacology, toxicity and pharmacokinetics of acetylshikonin: a review.Pharmaceutical biology · 2020Review
- Article
- Overexpression of ABCB1 Transporter Confers Resistance to mTOR Inhibitor WYE-354 in Cancer Cells.International journal of molecular sciences · 2020Article
- Competitive glucose metabolism as a target to boost bladder cancer immunotherapy.Nature reviews. Urology · 2020Review
- Reversal Effect of ALK Inhibitor NVP-TAE684 on ABCG2-Overexpressing Cancer Cells.Frontiers in oncology · 2020Article
- Effect of β-cyclodextrin encapsulation on cytotoxic activity of acetylshikonin against HCT-116 and MDA-MB-231 cancer cell lines.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2020Article
- The CK2 inhibitor CX4945 reverses cisplatin resistance in the A549/DDP human lung adenocarcinoma cell line.Oncology letters · 2019Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytotoxic activities of acetylshikonin and acetoxyisovalerylshikonin alone and in combination with chemotherapeutic agents against parental and drug resistant cell lines were determined using the MTT assay. Effects of Shikonin derivatives on BCRP, MDR1 and MRP transcript and protein levels were relatively measured. Finally, accumulation and efflux kinetics were conducted. The results revealed cell- and concentration-dependency of the cell cytotoxicity. Acetylshikonin and acetoxyisovalerylshikonin transiently made the mRNA ocean turbulent, but FACS analyses using fluorescent-labeled antibodies showed no significant change in the MDR-protein levels. Functional kinetics revealed significant block of MDR1, BCRP and MRP transporter in the presence of shikonin derivatives. Maximum accumulation fold changes was quantified to be 4.4 and consequently, acetoxyisovalerylshikonin pretreated EPG85.257RDB cells was chemosensitized to daunorubicin tension 3.1-fold. Although, the MDR blockage was reported to follow time- and cell-dependent patterns, MDR1, BCRP and MRP2 responses to the shikonins are concentration-independent. These data suggest uncompetitive transporter blockage behavior of these agents. The results indicated that shikonin derivatives stimulate uptake and reduce efflux of chemotherapeutic agents in the malignant cancer cells, suggesting that chemotherapy in combination with shikonin compounds may be beneficial to cancer cells that overexpress multidrug resistance transporters.
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