Anti-invasive activity of diallyl disulfide through tightening of tight junctions and inhibition of matrix metalloproteinase activities in LNCaP prostate cancer cells.
Diallyl disulfide (DADS) is a major component of an oil-soluble allyl sulfide garlic (Allium sativum) derivative, which has been shown to exert a potential for anti-cancer activity. However, the biochemical mechanisms underlying DADS-induced anti-invasiveness and anti-metastasis have not been thoroughly studied. In this study, we investigated the effect of DADS on the correlation between tightening of tight junctions (TJs) and anti-invasive activity in human prostate carcinoma LNCaP cells. Inhibitory effects of DADS on cell motility and invasiveness were found to be associated with increased tightness of the TJ, which was demonstrated by an increase in transepithelial electrical resistance (TER). Additionally, immunoblotting results indicated that DADS repressed the levels of the claudin proteins, which are major components of TJs that play a key role in control and selectivity of paracellular transport. Furthermore, the activities of matrix metalloproteinase (MMP)-2 and -9 in LNCaP cells were dose-dependently inhibited by treatment with DADS, and this was also correlated with a decrease in expression of their mRNA and proteins. Although further studies are needed, the present study indicates that TJs and MMPs are critical targets of DADS-induced anti-invasiveness in human prostate cancer LNCaP cells.
Shin
Dong Yeok
DY
Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan, Republic of Korea.
Kim
Gi-Young
GY
Kim
Jung-In
JI
Yoon
Moo Kyoung
MK
Kwon
Taeg Kyu
TK
Lee
Su Jae
SJ
Choi
Young-Whan
YW
Kang
Ho Sung
HS
Yoo
Young Hyun
YH
Choi
Yung Hyun
YH
D000498:Allyl Compounds / Q000494:pharmacology*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004220:Disulfides / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D011471:Prostatic Neoplasms; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism; D014410:Tumor Stem Cell Assay
D000498:Allyl Compounds; D016588:Anticarcinogenic Agents; D004220:Disulfides; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; C028009:diallyl disulfide; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9