Significant Activity of Ecdysteroids on the Resistance to Doxorubicin in Mammalian Cancer Cells Expressing the Human ABCB1 Transporter

详细信息    查看全文

• 作者：Ana Martins ; No茅mi T贸th ; Attila V谩nyol贸s ; Zolt谩n B茅ni ; Istv谩n Zupk贸 ; J贸zsef Moln谩r ; M谩ria B谩thori ; Attila Hunyadi
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：June 14, 2012
• 年：2012
• 卷：55
• 期：11
• 页码：5034-5043
• 全文大小：445K
• 年卷期：v.55,no.11(June 14, 2012)
• ISSN：1520-4804

文摘

Multidrug resistance (MDR) is a major cause of failure of cancer chemotherapy. Fifty-eight ecdysteroids, herbal analogues of the insect molting hormone and their semisynthetic derivatives, were tested for their activity against L5178 mouse T-cell lymphoma cells (non-MDR) and their subcell line transfected with pHa MDR1/A retrovirus overexpressing the human ABCB1 efflux pump (MDR cell line). The compounds showed very low antiproliferative activities but modulated the efflux of rhodamine 123 mediated by the ABCB1 transporter. Roughly depending on the polarity, mild to strong synergism or antagonism was observed by combining ecdysteroids with doxorubicin, and specific structure鈥揳ctivity relationships were also found. Our results show the effect of ecdysteroids on MDR cancer cells for the first time. Less polar derivatives may serve as valuable leads toward a potent and safe resistance modulator. Biological significance of the resistance-increasing activity of the most abundant phytoecdysteroids including 20-hydroxyecdysone is yet to be clarified.