ArticleMolecular cancer2010
Differential chemosensitization of P-glycoprotein overexpressing K562/Adr cells by withaferin A and Siamois polyphenols.
Article in Molecular cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
25 citing papers in PubMed, 76 citations in OpenAlex.
- Targeting PRDX1 impairs acute myeloid leukemic blasts and stem cells by disrupting redox homeostasis.Cell death & disease · 2025Article
- Withaferin A inhibits Chikungunya virus nsP2 protease and shows antiviral activity in the cell culture and mouse model of virus infection.PLoS pathogens · 2024Article
- Ceftriaxone-associated dysbiosis decreases voriconazole bioavailability by upregulating intestinal P-glycoprotein expression through activation of the Nrf2-mediated signalling pathway.Frontiers in pharmacology · 2024Article
- Alternations of NF-κB Signaling by Natural Compounds in Muscle-Derived Cancers.International journal of molecular sciences · 2023Review
- Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal PlantPharmaceuticals (Basel, Switzerland) · 2023Review
- Review
- Withaferin A: From Ancient Remedy to Potential Drug Candidate.Molecules (Basel, Switzerland) · 2021Review
- Marine Seagrass Extract ofMarine drugs · 2021Article
- Can NF-κB Be Considered a Valid Drug Target in Neoplastic Diseases? Our Point of View.International journal of molecular sciences · 2020Review
- South Asian Medicinal Compounds as Modulators of Resistance to Chemotherapy and Radiotherapy.Cancers · 2016Review
- Withaferin-A--A Natural Anticancer Agent with Pleitropic Mechanisms of Action.International journal of molecular sciences · 2016Review
- Long-Term Alteration of Reactive Oxygen Species Led to Multidrug Resistance in MCF-7 Cells.Oxidative medicine and cellular longevity · 2016Article
- Inhibition of the NF-κB signaling pathway by a novel heterocyclic curcumin analogue.Molecules (Basel, Switzerland) · 2015Article
- Hsp90 Inhibitors for the Treatment of Chronic Myeloid Leukemia.Leukemia research and treatment · 2015Review
- Cytotoxicity of dietary flavonoids on different human cancer types.Pharmacognosy reviews · 2014Review
- Article
- Molecular targets and mechanisms of cancer prevention and treatment by withaferin a, a naturally occurring steroidal lactone.The AAPS journal · 2014Review
- Apoptosis sensitization by Euphorbia factor L1 in ABCB1-mediated multidrug resistant K562/ADR cells.Molecules (Basel, Switzerland) · 2013Article
- Transcription factor CUTL1 is a negative regulator of drug resistance in gastric cancer.The Journal of biological chemistry · 2013Article
- Andrographis paniculata Extract and Andrographolide Modulate the Hepatic Drug Metabolism System and Plasma Tolbutamide Concentrations in Rats.Evidence-based complementary and alternative medicine : eCAM · 2013Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMultidrug resistance (MDR) is a major obstacle in cancer treatment and is often the result of overexpression of the drug efflux protein, P-glycoprotein (P-gp), as a consequence of hyperactivation of NFkappaB, AP1 and Nrf2 transcription factors. In addition to effluxing chemotherapeutic drugs, P-gp also plays a specific role in blocking caspase-dependent apoptotic pathways. One feature that cytotoxic treatments of cancer have in common is activation of the transcription factor NFkappaB, which regulates inflammation, cell survival and P-gp expression and suppresses the apoptotic potential of chemotherapeutic agents. As such, NFkappaB inhibitors may promote apoptosis in cancer cells and could be used to overcome resistance to chemotherapeutic agents.
resultsAlthough the natural withanolide withaferin A and polyphenol quercetin, show comparable inhibition of NFkappaB target genes (involved in inflammation, angiogenesis, cell cycle, metastasis, anti-apoptosis and multidrug resistance) in doxorubicin-sensitive K562 and -resistant K562/Adr cells, only withaferin A can overcome attenuated caspase activation and apoptosis in K562/Adr cells, whereas quercetin-dependent caspase activation and apoptosis is delayed only. Interestingly, although withaferin A and quercetin treatments both decrease intracellular protein levels of Bcl2, Bim and P-Bad, only withaferin A decreases protein levels of cytoskeletal tubulin, concomitantly with potent PARP cleavage, caspase 3 activation and apoptosis, at least in part via a direct thiol oxidation mechanism.
conclusionsThis demonstrates that different classes of natural NFkappaB inhibitors can show different chemosensitizing effects in P-gp overexpressing cancer cells with impaired caspase activation and attenuated apoptosis.
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