P-glycoprotein and its inhibition in tumors by phytochemicals derived from Chinese herbs

Eichhorn, Tolga; Efferth, Thomas

doi:10.1016/j.jep.2011.08.053

Cited by 95 publications

(62 citation statements)

References 187 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, patients with MDR tumor types often only have limited options, but can withstand significantly high doses (27). Thus, with the evidence that more new drugs are deriving from herbal medicines, quercetin, epigallocatechin gallate, curcumin, capsaicin and gingerol have (29), to bypass drug resistance in treating cancer, and eventually medicinal herbs may be applied in the future in cancer adjuvant therapy. Capsaicin (8) and gingerol (8) have been reported to exhibit inhibitory effects on human P-gp.…”

Section: Reversing Multidrug Resistancementioning

confidence: 99%

Efficacy of traditional Chinese medicine in treating cancer

et al. 2015

View full text Add to dashboard Cite

Section: Reversing Multidrug Resistancementioning

confidence: 99%

Efficacy of traditional Chinese medicine in treating cancer

et al. 2015

View full text Add to dashboard Cite

“…Inhibitors of ABCB1, as well as its non-toxic substrates, might be used to overcome drug resistance and understand the intestinal absorption of drugs. Much effort has been devoted to screening for natural phytochemicals, which can inhibit ABCB1-mediated transport, and thus have the potential application of reversing drug resistance [3].…”

Section: Introductionmentioning

confidence: 99%

Experimental and Simulation Identification of Xanthohumol as an Inhibitor and Substrate of ABCB1

Liu

Hoag

et al. 2018

Applied Sciences

View full text Add to dashboard Cite

Xanthohumol (XN) is a well-known prenylated flavonoid found in Humulus lupulus L. It is involved in several pharmacological activities, including the sensitization of doxorubicin-resistant breast cancer (MCF-7/ADR) cells to doxorubicin (DOX) through a reduction in cell viability and stemness. In the present study, we revealed another mechanism to further explain the reverse of the drug resistance of XN. In the MCF-7/ADR cell line, we found that XN inhibited the efflux functions of ATP-binding cassette subfamily B member 1 (ABCB1). We also observed that XN was a substrate of ABCB1 and stimulated its ATPase activity. Moreover, our results revealed that XN showed a synergic effect with the ABCB1 substrate colchicine (COL) in the MCF-7/ADR cell line. Further, we showed that XN bound to the central transmembrane domain (TMD) site, overlapping with the DOX binding site. This mechanism was supported by molecular modeling and simulation data, which revealed that XN bound to the ABCB1 transmembrane domain, where doxorubicin also binds, and its binding affinity was stronger than that of doxorubicin, resulting in less protein and ligand position fluctuation. These results support the XN-induced reversal of drug resistance via the inhibition of ABCB1-mediated transport of doxorubicin, stimulating ABCB1 ATPase activity and acting as a substrate of ABCB1.

show abstract

“…55 Efflux transporters have initially raised interest in cancer biology and clinical oncology as pumps for anticancer drugs that maintain the level of anticancer drugs at sublethal concentration in cancer cells thereby leading to threatened multidrug resistance phenotypes failure of chemotherapy and fatal outcome for cancer patients. [56][57][58][59] More recently, it was recognized that efflux transporters play a crucial role for the absorption and bioavailability of pharmaceuticals in general and xenobiotic compounds taken up with food. 12,60,61 This also implies a fundamental role of the evolutionary arms race between animals and plants.…”

Section: Evolutionary Arms Race Between Plants and Herbivoresmentioning

confidence: 99%

Animal plant warfare and secondary metabolite evolution

Wöll

Kim

Greten

et al. 2013

Nat. Prod. Bioprospect.

Self Cite

View full text Add to dashboard Cite

Abstract:The enduring discussion, why plants produce secondary metabolites with pharmacologically and toxicologically active towards mammals traces back to the eminent role of medicinal plants in the millennia-old history of manhood. In recent years, the concept of an animal plant warfare emerged, which focused on the co-evolution between plants and herbivores. As a reaction to herbivory, plants developed mechanical defenses such as thorns and hard shells, which paved the way for adapted animal physiques. Plants evolved further defense systems by producing chemicals that exert toxic effects on the animals that ingest them. As a result of this selective pressure, animals developed special enzymes, e.g. cytochrome P450 monooxigenases (CYP450) that metabolize xenobiotic phytochemicals. As a next step in the evolutionary competition between plants and animals, plants evolved to produce non-toxic pro-drugs, which become toxic only after ingestion by animals through metabolization by enzymes such as CYP450. Because these sequestered evolutionary developments call to mind an arms race, the term animal plant warfare has been coined. The evolutionary competition between plants and animals may help to better understand the modes of action of medicinal plants and to foster the efficient and safe use of phytotherapy nowadays.

show abstract

P-glycoprotein and its inhibition in tumors by phytochemicals derived from Chinese herbs

Cited by 95 publications

References 187 publications

Efficacy of traditional Chinese medicine in treating cancer

Efficacy of traditional Chinese medicine in treating cancer

Experimental and Simulation Identification of Xanthohumol as an Inhibitor and Substrate of ABCB1

Animal plant warfare and secondary metabolite evolution

Contact Info

Product

Resources

About