Naturally-occurring shikonin analogues--a class of necroptotic inducers that circumvent cancer drug resistance.
We previously reported that shikonin could circumvent drug resistance mediated by P-gp, Bcl-2 and Bcl-xL, by induction of necroptosis. Here, we show that the naturally-occurring shikonin analogues (deoxyshikonin, acetylshikonin, isobutyrylshikonin, beta,beta-dimethylacrylshikonin, isovalerylshikonin, alpha-methyl-n-butylshikonin) could bypass drug resistance mediated by not only P-gp, Bcl-2, and Bcl-xL, but also two additional important drug-resistant factors MRP1 and BCRP1, by induction of necroptosis. The results strengthen the previous findings that necroptotic induction could circumvent a broad spectrum of cancer drug resistance.
Xuan
Yanyan
Y
Cancer Institute, The Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
Hu
Xun
X
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D004586:Electrophoresis; D005434:Flow Cytometry; D006801:Humans; D008854:Microscopy, Electron; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000502:physiology; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D051020:bcl-X Protein / Q000502:physiology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D053148:Caspase 3; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009285:Naphthoquinones; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; C116614:ABCG2 protein, human; C016101:shikonin; C421109:multidrug resistance-associated protein 1