title: Reversal effects of two new milbemycin compounds on multidrug resistance in MCF-7/adr cells in vitro.
abstract: Development of agents to overcome multidrug resistance (MDR) is important in cancer chemotherapy, and the overexpression of P-glycoprotein (P-gp) is one of the major mechanisms of MDR. In this paper, we evaluated the effects of two new milbemycin compounds, milbemycin β(14) and secomilbemycin D, isolated from fermentation broth of S. bingchenggensis on reversing MDR of adriamycin-resistant human breast carcinoma (MCF-7/adr) cells. We observed that the both milbemycins (5 μM) showed strong potency to increase adriamycin cytotoxicity toward MCF-7/adr cells with reversal fold (RF) of 13.5 and 10.59, respectively. In addition, the mechanisms of milbemycins on reversing P-gp-mediated MDR demonstrated that they significantly increased the accumulations of adriamycin and Rh123 via inhibiting P-gp efflux in MCF-7/adr cells. Furthermore, the results also revealed that milbemycin β(14) and secomilbemycin D could regulate down the expression of P-gp, but not affect the expression of MDR1 gene. In conclusion, our observations suggest that the two new milbemycin compounds probably represent the promising agents for reversing MDR in cancer therapy.
authors: School of Life Science, Northeast Agricultural University, Harbin, China.
authors: Aili
authors: A
authors: Gao
authors: Hongsheng
authors: H
authors: Liang
authors: Xiangjing
authors: X
authors: Wang
authors: Xiangtong
authors: X
authors: Zhang
authors: Meng
authors: M
authors: Jing
authors: Ji
authors: J
authors: Zhang
authors: Yijun
authors: Y
authors: Yan
authors: Wensheng
authors: W
authors: Xiang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D018942:Macrolides / Q000737:chemistry / Q000494:pharmacology; D020112:Rhodamine 123 / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018942:Macrolides; C548487:secomilbemycin D; D020112:Rhodamine 123; D004317:Doxorubicin; C027837:moxidectin