International Journal of Molecular and Cellular Medicine
مجله بین المللی سلولی و مولکولی
Int J Mol Cell Med
Medical Sciences
http://ijmcmed.org
1
admin
2251-9637
2251-9645
10.22088/IJMCM.BUMS
en
jalali
1395
4
1
gregorian
2016
7
1
5
3
online
1
fulltext
en
Genistein Induces Apoptosis and Inhibits Proliferation of HT29 Colon Cancer Cells
Cancer
Cancer
Original Article
Original Article
<p dir="ltr" style="text-align: justify;">Soybean isoflavone genistein has multiple anticancer properties and its pro-apoptotic and anti-proliferative effects have been studied in different cancer cells. However, the mechanisms of action of genistein and its molecular targets on human colon cells have not been fully elucidated. Therefore, caspase-3 and p38 mitogen-activated protein kinase (p38 MAPK) as the main therapeutic targets were investigated in this study at both gene expression and protein levels in HT29 colon cancer cells. The caspase-3 and <em>p38 MAPK </em>gene expression levels were examined by real time PCR whereas flow cytometry technique was performed to determine their intracellular protein levels. The caspase-3 enzyme activity was obtained by colorimetric method while the gelatinase activity of matrix metalloproteinase-2 (MMP2) was determined by zymography. In addition, MTT test, wound healing assay and clonogenic assay were carried out to determine the effect of genistein on HT29 cell viability, migration, and proliferation, respectively. Genistein induced apoptotic death in HT29 cells through activation of caspase-3 pathway at the transcriptional, protein, and enzymatic levels. Moreover, genistein inhibited the proliferation of HT29 cells by reducing of both <em>p38 MAPK</em> gene expression and its active phosphorylated protein level. Also, we showed that genistein strongly suppressed the metastatic potency of HT29 colon cancer cells via the reduction of MMP2 activity. Based on the results of this study, we conclude that genistein may exhibit its anticancer properties on HT29 colon cancer cells by modulating caspase-3 and p38 MAPK pathway at different transcriptional and protein levels.</p>
Apoptosis, Caspase-3, Colonic neoplasms, Genistein, p38 Mitogen-Activated Protein Kinases
178
191
http://ijmcmed.org/browse.php?a_code=A-10-794-1&slc_lang=en&sid=1
Gholamreza
Shafiee
g.r_shafiee@yahoo.com
10031947532846007759
10031947532846007759
No
Department of Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Massoud
Saidijam
sjam110@yahoo.com
10031947532846007760
10031947532846007760
No
Department of Molecular Medicine and Human Genetics, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan-Iran
Heidar
Tavilani
tavilani@gmail.com
10031947532846007761
10031947532846007761
No
Department of Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Neda
Ghasemkhani
neda.ghasemkhani@gmail.com
10031947532846007762
10031947532846007762
No
Department of Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Iraj
Khodadadi
khodadadi@umsha.ac.ir
10031947532846007763
10031947532846007763
Yes
Department of Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.