PEITC做為未來口腔癌化學預防與治療藥物的發展潛力
Study on the Potential Usage of phenethyl isothiocynate for the Treatment of Oral Cancer
Date Issued
2005
Date
2005
Author(s)
Yang, Ching-Chin
DOI
en-US
Abstract
Oral cancer is the fourth leading cause of cancer-related deaths in male population in Taiwan. Despite recent advances in radiotherapy and chemotherapy, the survival of patients with oral cancer has not improved significantly. Continued investigation of new chemotherapeutic agents is thus needed. Recent studies have shown that feeding phenylethyl isothiocyanate (PEITC) inhibited carcinogen-induced mouse oral carcinogenesis. However, the mechanisms by which it inhibits oral carcinogenesis are not well understood.
The present study examined the effects of PEITC on proliferation, cell cycle and apoptosis of oral cancer cell lines SAS using trypan blue assay, flow cytometry analysis, DAPI assay and Western blot analysis. PEITC significantly inhibited the proliferation of SAS oral cancer cell lines in a dose-dependent manner with a 50% inhibition concentration (IC50) of PEITC about 7.5 μM. DNA flow cytometric analysis showed that PEITC treatment induced a G2/M arrest. PEITC treatment also caused significant apoptosis of SAS cells as evidenced by DAPI staining, increase of cytochorme C release and cleavage of PARP. These results indicate that the inhibitory effects of PEITC on oral carcinogenesis may be related to the G2/M phase arrest and induction of apoptosis. The PEITC induced cell cycle arrest was associated with the increase of p21, p27 protein, but not the protein levels of Cdk1 and cyclin B1. We also found PEITC enhanced the expression of p53 and Bax in SAS cells. In addition, PEITC decreased the expression of Bcl-2 in SAS. PEITC treatment also induced the expression of death receptors, Fas and DR5. Furthermore, PEITC could induce the activation of caspase 8 and caspase 9 in SAS cells. The PEITC-induced apoptosis was significantly attenuated in the presence of specific inhibitors of caspase-8 and caspase-9. These results suggest that apoptosis occurred via both the mitochondria mediated and death receptor mediated pathway.
The MAPK family of serine/threonine kinases, including extracellular signal-regulated kinase1/2 (ERK1/2), c-jun N-terminal kinase1/2/3 (JNK1/2/3), and p38 MAPK play an important role in cell proliferation and apoptosis in response to different stimuli. We found JNK and ERK were activated shortly after PEITC treatment in SAS cells. In addition, JNK inhibitor SP600125 and the ERK inhibitor PD98059 suppressed apoptosis induced by PEITC. These results indicate that MAPKs involve in apoptosis induction by PEITC in human oral cancer cells.
Subjects
異硫氰酸苯乙酯
細胞凋亡
口腔癌
細胞週期
PEITC
SAS cell
apoptosis
MAPK kinase
G2/M cell cycle arrest
SDGs
Type
other
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