为癌症治疗解绑半胱氨酸天冬氨酸蛋白酶 7。
Unshackling caspase-7 for cancer therapy.
机构信息
Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
出版信息
J Clin Invest. 2013 Sep;123(9):3706-8. doi: 10.1172/JCI71440. Epub 2013 Aug 27.
Abstract
Numerous solid tumors and hematologic malignancies acquire resistance to apoptosis-inducing chemotherapeutic drugs by downregulating the key effector caspase-3. These cells rely on caspase-7 to execute the apoptotic program, yet binding with XIAP constitutively inhibits active caspase-7 (p19/p12-CASP7). In this issue, Lin et al. describe how a newly synthesized drug is able to disrupt the XIAP:p19/p12-CASP7 complex and induce apoptosis in caspase-3-deficient cancer cells in vitro and in vivo. As this compound appears to exhibit minimal toxicity on normal tissues, it may represent a promising therapeutic agent to help treat caspase-3-deficient tumors.
摘要
许多实体肿瘤和血液恶性肿瘤通过下调关键效应子半胱天冬酶-3 来获得对诱导细胞凋亡的化疗药物的耐药性。这些细胞依赖半胱天冬酶-7 来执行凋亡程序，但 XIAP 的结合会持续抑制活性半胱天冬酶-7（p19/p12-CASP7）。在本期中，Lin 等人描述了一种新合成的药物如何能够破坏 XIAP:p19/p12-CASP7 复合物，并在体外和体内诱导 caspase-3 缺陷型癌细胞凋亡。由于该化合物对正常组织的毒性似乎很小，因此它可能代表一种有前途的治疗药物，有助于治疗 caspase-3 缺陷型肿瘤。
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