Targeting the weak point of cancer by induction of necroptosis.
Targeting the "weak point" of cancers, especially the apoptotic/drug resistant cancers, is critical for the success of cancer chemotherapy. We found that the drug resistant cancer cell lines overexpressing P-gp, MRP1, BCRP, Bcl-2 and Bcl-xL are susceptible to shikonin, a necroptotic inducer, despite the fact that they are highly resistant to a variety of anticancer agents such as anthracycline antibiotics, vinca alkaloids, taxanes, epipodophylotoxins, etc. These findings reveal that, although apoptotic/drug resistance is a formidable "stronghold" of cancer against chemotherapy, necroptotic susceptibility is an intrinsic "weak point" of cancer. Therefore, targeting the weakness of cancer by induction of necroptosis may have significant potential in cancer chemotherapy, especially in the apoptotic/drug resistant cancers.
Hu
Xun
X
Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China. huxun@zju.edu.cn
Han
Weidong
W
Li
Ling
L
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*
D000970:Antineoplastic Agents