Sulforaphane induces G2-M arrest and apoptosis in high metastasis cell line of salivary gland adenoid cystic carcinoma.
New chemotherapeutic strategy should be investigated to enhance clinical management in salivary gland adenoid cystic carcinoma (ACC). Recently, sulforaphane (SFN), as a natural compound from cruciferous vegetables exhibits a potent anti-cancer activity in various tumor cells, but remains uncertain in ACC cells. The present study examined whether SFN suppresses proliferation and in ACC cells, if so, the possible molecular targets would be further investigated. Cell survives, apoptosis, cell cycle progression and molecular targets were identified by multiple detecting techniques, including trypan blue dye exclusion assay, electron microscopy, AO/EB staining, flow cytometry and immunoblotting in human lung high metastasis cell line of salivary gland adenoid cystic carcinoma (ACC-M). The results showed that 5-20 microM SFN suppressed proliferation and induced apoptosis of ACC-M cells in dose- and time-dependent manners. Cell cycle analysis demonstrated treatment of ACC-M cells with 20 microM SFN resulted in G(2)/M cell cycle arrest, which was associated with a marked decline in protein levels of G(2)/M regulatory proteins including cyclin B1 and cyclin-dependent kinase 1 (Cdk1). In terms of apoptosis, SFN increased the expression of Bax and decreased the level of Bcl-2 and subsequently triggered release of cytochrome c from mitochondria and activation of caspase-3, but Fas level and caspase-8 activity remained unchanged at all time points. Furthermore, levels of nuclear factor-kappaB (NF-kappaB) p65 in both of the cytoplasm and the nucleus have also been markedly suppressed by SFN in a time-dependent manner. Taken together, these results suggest SFN inhibits cell growth via inducing G(2)/M cell arrest and apoptosis in ACC-M cells. These events have been associated with SFN-regulated multiple targets involved in ACC-M cell proliferation. The present study provides an evidence for testing SFN efficacy in vivo and warranting future investigations to exam the clinical potential of SFN in ACC chemotherapy.
Chu
Wen-Feng
WF
Department of Pharmacology, Harbin Medical University, Baojian Road 157, Harbin, Heilongjiang 150081, PR China.
Wu
Dong-Mei
DM
Liu
Wei
W
Wu
Li-Jun
LJ
Li
De-Zhi
DZ
Xu
Dong-Yang
DY
Wang
Xiao-Feng
XF
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D003528:Carcinoma, Adenoid Cystic / Q000188:drug therapy* / Q000556:secondary; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D005136:Eye Proteins / Q000378:metabolism; D006801:Humans; D017879:Isothiocyanates; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008565:Membrane Proteins / Q000378:metabolism; D012468:Salivary Gland Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D051017:Apoptosis Regulatory Proteins; D005136:Eye Proteins; C406963:G2s protein, human; D017879:Isothiocyanates; D008565:Membrane Proteins; D013454:Sulfoxides; D013861:Thiocyanates; C016766:sulforaphane