Induction of Apoptosis in Human Leukemic Cell Lines by Diallyl Disulfide via Modulation of EGFR/ERK/PKM2 Signaling Pathways.
BACKGROUND
Diallyl disulfide (DADS) may exert potent anticancer action both in vitro and in vivo. Although its effects on cancer are significant, the underlying mechanisms remain unknown. In this study, we sought to elucidate possible links between DADS and pyruvate kinase (PKM2).


METHODS
KG1α, a leukemia cell line highly expressing PKM2 was used with a cell counting kit (CCK)-8 and flow cytometry (FCM) to investigate the effects of DADS. Relationships between PKM2 and DADS associated with phosphorylation of EGFR, ERK1/2 and MEK, were assessed by western blot analysis.


RESULTS
In KG1α cells highly expressing PKM2, we found that DADS could affect proliferation, apoptosis and EGFR/ERK/PKM2 signaling pathways, abrogating EGF-induced nuclear accumulation of PKM2.


CONCLUSIONS
These results suggested that DADS suppressed the proliferation of KG1α cells, providing evidence that its proapoptotic effects are mediated through the inhibition of EGFR/ERK/PKM2 signaling pathways.
Laboratory of Stem Cells and Tissue Engineering, Histology and Embryology, Chongqing Medical University, Chongqing, China E-mail : lijingyangyang@126.com.cn.
Nian
N
Luo
Lv-Cui
LC
Zhao
Qing-Qiang
QQ
Shi
Zi-Qiang
ZQ
Feng
Di-Long
DL
Chen
Jing
J
Li
D000498:Allyl Compounds / Q000494:pharmacology*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004220:Disulfides / Q000494:pharmacology*; D066246:ErbB Receptors / Q000187:drug effects* / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D007938:Leukemia; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008565:Membrane Proteins / Q000187:drug effects* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013963:Thyroid Hormones / Q000378:metabolism; D000097810:Thyroid Hormone-Binding Proteins
D000498:Allyl Compounds; D016588:Anticarcinogenic Agents; D002352:Carrier Proteins; D004220:Disulfides; D066246:ErbB Receptors; D008565:Membrane Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins; C028009:diallyl disulfide; C512478:EGFR protein, human; C535150:MAPK1 protein, human