The pterocarpanquinone LQB 118 induces apoptosis in tumor cells through the intrinsic pathway and the endoplasmic reticulum stress pathway.
ANTI-CANCER DRUGS(2013)
摘要
LQB 118 is a pterocarpanquinone compound synthesized by our group. It has already been shown that it acts against different leukemia cell lines. However, little is known about the pathway through which this compound induces the death of these cells. In this work, we analyzed the cell death process induced by LQB 118 in K562, a chronic myeloid leukemia cell line, and in Jurkat, a lymphoblastic acute leukemia cell line. For this, we carried out a cell viability assay by MTT, an apoptosis/necrosis assay through the annexin/propidium iodide label, cell cycle by flow cytometry, assessed changes in the mitochondrial membrane potential using DiOC6( 3), cytoplasmic calcium analysis by Fluo-3-AM, and a caspase-9 and caspase-12 activity assay. We found that LQB 118 induced apoptosis in both cell lines, measuring caspase-12 and caspase-9 activation, phosphatidylserine externalization, and DNA fragmentation. The compound induced an increase in cytoplasmic calcium on both cell lines. However, the compound could only induce mitochondrial membrane depolarization on K562 cells. Our data show that LQB 118 may have potential therapeutic value for leukemia, being able to overcome multiple resistance mechanisms. Anti-Cancer Drugs 24: 73-83 (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.
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关键词
apoptosis,endoplasmic reticulum stress,leukemia,mitochondria,pterocarpanquinone
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