AI Article Synopsis
- Multidrug resistance (MDR) in cancer treatment is often caused by overexpression of P-glycoprotein (P-GLP), which reduces the effectiveness of chemotherapy drugs like doxorubicin (DOX).
- Ailanthone (AIL), a natural compound from Ailanthus altissima, has been found to reverse P-GLP-induced MDR and enhance the effectiveness of DOX in resistant K562/A02 cancer cells.
- AIL works by increasing DOX accumulation in the cells, inhibiting the activity and expression of P-GLP, and interfering with the PI3K/Akt signaling pathway, making it a promising option for combating drug-resistant cancers.
Article Abstract
Multidrug resistance (MDR) poses a great impediment to cancer treatment. Excessive expression of ATP-binding cassette transport protein AC-1 (P-glycoprotein, P-GLP) is usually involved in MDR. In this study, ailanthone (AIL), a natural compound extracted from the whole seedlings of Ailanthus altissima (Simaroubaceae) was shown to mediate the reversal of P-GLP-induced MDR and restore the susceptibility of K562/A02 cells to doxorubicin (DOX). Further mechanistic studies revealed that AIL increased intracellular DOX accumulation and interrupted Rh123 efflux through suppression of P-GLP, and also suppressed P-GLP ATPase activity. At the same time, it markedly inhibited MDR1 gene expression and P-GLP protein to sensitize the cytotoxic effect of DOX. Furthermore, AIL down-regulated P-GLP expression by inhibiting the PI3K/Akt pathway. Thus, AIL could be a potential therapeutic compound for reversing P-GLP-mediated drug resistant cancer.
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