Department of Oral Pathology, School of Dentistry, Institute of Oral Bioscience, Brain Korea 21, Chonbuk National University, Jeonju, Jeonju, Korea.
Oral Dis. 2012 Jul;18(5):513-9. doi: 10.1111/j.1601-0825.2012.01905.x. Epub 2012 Feb 6.
β-Phenylethyl isothiocyanate (PEITC) has been demonstrated to fight many types of cancers through various molecular pathways. In this study, we focused on its effect on the induction of apoptosis to inhibit cell growth and molecular mechanism in oral cancer.
3-(4,5-dimethylthiazol-2-yl)-5-(2,4-disulfophenyl)-2-(4 sulfophenyl)-2H-tetrazolium (MTS) assay was used to examine cell viability. The apoptotic effect was investigated using 4'-6-Diamidino-2-phenylindole (DAPI) staining or Western blotting. Inhibitors were used to determine the molecular target and mechanism of PEITC-mediated apoptosis.
β-Phenylethyl isothiocyanate inhibited the growth of HN22 human oral cancer cells and induced caspase-dependent apoptosis in HN22 cells as evidenced by nuclear fragmentation and the activation of caspase 3. It increased cleaved caspase 8, truncated BID, and death receptor 5 (DR5) through the activation of p38 MAPK. This result was confirmed by blockage of PEITC-induced cleavages of Poly(ADP-ribose) Polymerase, caspase-3, caspase-8, and DR5 by p38 MAPK inhibitor, SB203580. We also found that PEITC activated p38 and augmented DR5 to induce apoptosis in other human oral cancer cells.
These results suggest that DR5 is a potential molecular target for PEITC-induced apoptosis in oral cancer via p38 MAPK.
β-苯乙基异硫氰酸酯（PEITC）已被证明通过多种分子途径对抗多种类型的癌症。在本研究中，我们专注于其诱导细胞凋亡的作用，以抑制口腔癌细胞生长和分子机制。
使用 3-(4,5-二甲基噻唑-2-基)-5-(2,4-二磺基苯基)-2-(4-磺基苯基)-2H-四唑（MTS）测定法来检测细胞活力。通过 4'-6-二脒基-2-苯基吲哚（DAPI）染色或 Western blot 来研究凋亡效应。使用抑制剂来确定 PEITC 介导的凋亡的分子靶标和机制。
β-苯乙基异硫氰酸酯抑制人口腔癌细胞 HN22 的生长，并诱导 HN22 细胞中 caspase 依赖性凋亡，表现为核片段化和 caspase 3 的激活。它通过激活 p38 MAPK 增加了裂解的 caspase 8、截断的 BID 和死亡受体 5（DR5）。这一结果通过 p38 MAPK 抑制剂 SB203580 阻断 PEITC 诱导的多聚（ADP-核糖）聚合酶、caspase-3、caspase-8 和 DR5 的裂解得到证实。我们还发现 PEITC 通过激活 p38 并增加 DR5 来诱导其他人口腔癌细胞发生凋亡。
这些结果表明，DR5 是 PEITC 通过 p38 MAPK 诱导口腔癌细胞凋亡的潜在分子靶标。
