LukS-PV, a component of Panton-Valentine leukocidin, exerts potent activity against acute myeloid leukemia in vitro and in vivo

Shan, Wulin; Bu, Su; Zhang, Chengfang; Zhang, Shanshan; Ding, Bangsheng; Chang, Wenjiao; Dai, Yuanyuan; Shen, Jilong; Ma, Xiaoling

doi:10.1016/j.biocel.2015.01.007

Cited by 16 publications

(20 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data implied that the mitochondrial pathway was involved in the apoptotic process induced by LukS-PV for myelogenous leukemia cells (Fig. 1), which was similar to Lee (Lee et al, 2005;Bu et al, 2013;Shan et al, 2015).…”

Section: Luks-pv Induces Apoptosis In Human Myelogenous Leukemia Cellsupporting

confidence: 55%

“…LukS-PV specifically had the anti-leukemia activity for THP-1 and HL-60 cells, but not to A549, jurkat or HeLa cells (Bu et al, 2013;Shan et al, 2015). Spaan et al reported LukS-PV could bind to human neutrophils and monocytes but not to lymphocytes (Spaan et al, 2013), suggesting a specific affinity between LukS-PV and myeloid cells.…”

Section: Potential Activity Of Luks-pv For Other Types Of Leukemiamentioning

confidence: 95%

“…Like this, we could try to produce genetically modified or recombinant toxins, achieved by deleting the DNA coding for the toxin binding region, to reduce toxicity of PVL. Although several studies have demonstrated that LukS-PV was not cytotoxic in vitro and in vivo when applied alone (Genestier et al, 2005;Holzinger et al, 2012;Shan et al, 2015), whether LuckS-PV was toxic at higher concentrations has been lacking. Another major concern regarding LukS-PV therapy was low rate of leukemia cell differentiation.…”

Section: Problems With Luks-pv Therapy For Leukemiamentioning

confidence: 97%

“…The use of all-trans retinoic acid (ATRA) has seen remarkable clinical success for the acute promyelocytic leukemia subtype. We have demonstrated that LukS-PV had the ability to induce leukemia cell differentiation (Shan et al, 2015). Our recent studies were to investigate the mechanism involved in LukS-PV-induced cell differentiation.…”

Section: Luks-pv Induces Human Myelogenous Leukemia Cell Differentiationmentioning

confidence: 98%

“…c o m / l o c a t e / g e n e toxins, including denileukin diftitox, PA-MSHA, Clostridium perfringens enterotoxin, bacterial enterotoxin ST and leukotoxin, have been shown to selectively kill tumor cells (Michl et al, 2001;Duvic et al, 2002;Chang et al, 2009;Kachlany, 2010;Xu et al, 2014). In recent years, we have demonstrated that LukS-PV, a component of Panton-Valentine leukocidin (PVL) secreted by S. aureus, possessed certain antileukemia activity such as inducing leukemia cell differentiation and apoptosis, thus making LukS-PV a promising new treatment strategy for leukemia (Bu et al, 2013;Shan et al, 2015). This review will highlight the use of LukS-PV for leukemia therapy.…”

Section: Contents Lists Available At Sciencedirectmentioning

confidence: 99%

See 4 more Smart Citations

Is LukS-PV a novel experimental therapy for leukemia?

Shan

Deng

2017

Gene

Self Cite

View full text Add to dashboard Cite

Section: Luks-pv Induces Apoptosis In Human Myelogenous Leukemia Cellsupporting

confidence: 55%

Section: Potential Activity Of Luks-pv For Other Types Of Leukemiamentioning

confidence: 95%

Section: Problems With Luks-pv Therapy For Leukemiamentioning

confidence: 97%

Section: Luks-pv Induces Human Myelogenous Leukemia Cell Differentiationmentioning

confidence: 98%

Section: Contents Lists Available At Sciencedirectmentioning

confidence: 99%

See 3 more Smart Citations

Is LukS-PV a novel experimental therapy for leukemia?

Shan

Deng

2017

Gene

Self Cite

View full text Add to dashboard Cite

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

Zhang

Peng

et al. 2019

Cancer Medicine

View full text Add to dashboard Cite

LukS‐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 induced 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 antagonist 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 expression 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‐apoptotic Bax and Bak genes and proteins was downregulated while that of anti‐apoptotic Bcl‐2 and Bcl‐x genes and proteins was upregulated. Knockdown of C5aR also decreased LukS‐PV–induced THP‐1 cell apoptosis. LukS‐PV did not induce apoptosis of Jurkat cells, which have no endogenous C5aR expression; however, LukS‐PV did induce apoptosis in Jurkat cells after overexpression of C5aR. Correspondingly, the MMP decreased and Bax and Bak were upregulated while Bcl‐2 and Bcl‐x were downregulated. LukS‐PV can induce apoptosis in AML cells by targeting C5aR. C5aR may be a potential therapeutic target for AML and LukS‐PV is a candidate targeted drug for the treatment of AML.

show abstract