The Anticancer Agent Prodigiosin Is Not a Multidrug Resistance Protein Substrate
The Anticancer Agent Prodigiosin Is Not a Multidrug Resistance Protein Substrate
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DOI：
10.1089/dna.2012.1902
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发表时间：
2013-03-01
影响因子：
3.1
通讯作者：
Mirzaei, Seyed Abbas
中科院分区：
文献类型：
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作者：
Elahian, Fatemeh;Moghimi, Bahareh;Mirzaei, Seyed Abbas
明亮的红色色素是由革兰氏阴性和革兰氏阳性细菌产生的天然次生代谢物。这些分子因其抗菌、抗真菌、免疫抑制和抗癌活性而受到广泛关注。本研究分离了粘质沙雷氏菌SER1菌株，并用16s rDNA进行了验证。用硅胶层析法纯化了子芥子素，并用h -1 nmr对其进行了分析。分析纯化的子芥子素对过表达MDR1、BCRP或MRP2泵的多种耐药细胞系的细胞毒性作用。与亲本系相比，Prodigiosin对抗性细胞具有几乎相同的细胞毒性作用。与相同的细胞毒性一致，FACS分析了MDR过表达细胞系中prodigiosin的积累和外排，也表明这种促凋亡药物独立于MDR1、BCRP或MRP转运体的存在而起作用，可能是过度表达多药耐药转运体的恶性癌细胞的潜在治疗方法。
The brilliant red pigments prodiginines are natural secondary metabolites that are produced by select species of Gram-negative and Gram-positive bacteria. These molecules have received significant attention due to their reported antibacterial, antifungal, immunosuppressive, and anticancer activities. In this study, a Serratia marcescens SER1 strain was isolated and verified using 16s rDNA. The prodigiosin was purified using silica chromatography and was analyzed by H-1-NMR spectroscopy. The cell cytotoxic effects of the purified prodigiosin on multiple drug resistant cell lines that overexpress MDR1, BCRP, or MRP2 pumps were analyzed. Prodigiosin had nearly identical cytotoxic effects on the resistant cells in comparison to their parental lines. In agreement with the same prodigiosin cytotoxicity, FACS analysis of prodigiosin accumulation and efflux in MDR over-expressing cell lines also indicated that this pro-apoptotic agent operates independently of the presence of the MDR1, BCRP, or MRP transporter and may be a potential treatment for malignant cancer cells that overexpress multidrug resistance transporters.