P-glycoprotein (P-gp) is a major factor in the multidrug resistance phenotype in cancer cells. P-gp is a protein that regulates the ATP-dependent efflux of a wide range of anticancer medicines and confers resistance. Due to its wide specificity, several attempts have been made to block the action of P-gp to restore the efficacy of anticancer drugs. The major goal has been to create molecules that either compete with anticancer medicines for transport or function as a direct P-gp inhibitor. Despite significant in vitro success, there are presently no drugs available in the clinic that can “block” P-gp–mediated resistance. Toxicity, unfavourable pharmacological interactions, and a variety of pharmacokinetic difficulties might all be the reason for the failure. On the other hand, P-gp has a significant effect in the body. It protects the vital organs from the entry of foreign bodies and other toxic chemicals. Hence, the inhibitors of P-gp should not hinder its action in the normal cells. To develop an effective inhibitor of P-gp, thorough background knowledge is needed in this field. The main aim of this review article was to set forth the merits and demerits of the action of P-gp on cancer cells as well as on normal cells. The influence of P-gp on cancer drug delivery and the contribution of P-gp to activating drug resistance were also mentioned.
P-glycoprotein (P-gp) is an active member of the ATP Binding Cassette (ABC) protein subfamily which effluxes a wide range of therapeutic drugs out of the cells commonly known as multidrug resistance. But its protective action towards the normal cells and efflux of the toxic and foreign substances is remarkable. Hence the efflux of the P-gp is a crucial step to overcome for the success of the therapy and in the drug discovery process. Modification of the action of the P-gp through various inducers, inhibitors or the genetic polymorphism is the commonly used methods. When it comes to the inhibitor part the natural inhibitors use is more safe and economical as compared to the synthetic ones. Here we review at the mechanism of action and the pharmacokinetic profile of P-gp, how the P-gp engaged in the Multidrug resistance, the strategy to overcome from its action by using natural inhibitors and formulation perspectives.
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