LukS ‐PV induces apoptosis in acute myeloid leukemia cells mediated by C5a receptor

LukS ‐PV can induce apoptosis in acute myeloid leukemia (AML) cells through C5a receptor (C5aR), implicating C5aR as a potential target and LukS‐PV as a targeted drug for the treatment of AML AbstractLukS ‐PV is one of the two components of Panton‐Valentine leucocidin (PVL). Our previous study showed that LukS‐PV can induce apoptosis in human acute myeloid leukemia (AML) THP‐1 and HL‐60 cells. C5aR (C5a receptor) is the receptor for PVL, but whether C5aR plays a key role in LukS‐PV induce d apoptosis is unclear. The aim of this study was to establish whether C5aR plays a physiological role in apoptosis of leukemia cells induced by LukS‐PV. We investigated the role of C5aR in leukemia cell apoptosis induced by LukS‐PV by pretreatment of THP‐1 and HL‐60 cells with C5aR antagoni st and transfection to knockdown C5aR in THP‐1 cells or overexpress C5aR in Jurkat cells before treatment with LukS‐PV. Cell apoptosis was analyzed by staining with Annexin V/propidium iodide or Annexin V‐PE/7‐AAD. Mitochondrial membrane potential (MMP) was determined using JC‐1 dye. The e xpression of apoptosis‐associated genes and proteins was identified by qRT‐polymerase chain reaction and Western blotting analysis, respectively. As the C5aR antagonist concentration increased, the rate of apoptosis induced by LukS‐PV decreased, the MMP increased, and expression of pro‐apopt otic Bax and Bak genes and proteins was downregulated while that of anti‐apoptotic Bc...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research