Mondal Arindam, Biswas Raktim, Rhee Yun-Hee, Kim Jongkee, Ahn Jin-Chul
Beckman Laser Institute Korea, Dankook University, 119, Dandae-ro, Cheonan, Chungnam, 330-714, Republic of Korea.
Gen Physiol Biophys. 2016 Jan;35(1):25-34. doi: 10.4149/gpb_2015033. Epub 2015 Nov 27.
Gastric cancer migration and invasion considered as main causes of this cancer-related death around the world. Sulforaphene (4-isothiocyanato-4R-(methylsulfinyl)-1-butene), a structural analog of sulforaphane, has been found to exhibit anticancer potential against different cancers. Our aim was to investigate whether dietary isothiocyanate sulforaphene (SFE) can promote human gastric cancer (AGS) cells apoptosis and inhibit migration. Cells were treated with various concentrations of SFE and cell viability, morphology, intracellular ROS, migration and different signaling protein expressions were investigated. The results indicate that SFE decreases AGS cell viability and induces apoptosis in a dose-dependent manner. Intracellular ROS generation, dose- and time-dependent Bax/Bcl2 alteration and signaling proteins like cytochrome c, Casp-3, Casp-8 and PARP-1 higher expression demonstrated the SFE-induced apoptotic pathway in AGS cells. Again, SFE induced apoptosis also accompanied by the phosphorylation of mitogen-activated protein kinases (MAPKs) like JNK and P-38. Moreover, dose-dependent EGFR, p-ERK1/2 down-regulation and cell migration inhibition at non-toxic concentration confirms SFE activity in AGS cell migration inhibition. Thus, this study demonstrated effective chemotherapeutic potential of SFE by inducing apoptisis as well as inhibiting migration and their preliminary mechanism for human gastric cancer management.
胃癌的转移和侵袭被认为是全球癌症相关死亡的主要原因。萝卜硫素（4-异硫氰酸酯-4R-（甲基亚磺酰基）-1-丁烯）是萝卜硫素的结构类似物，已被发现对不同癌症具有抗癌潜力。我们的目的是研究膳食异硫氰酸酯萝卜硫素（SFE）是否能促进人胃癌（AGS）细胞凋亡并抑制其迁移。用不同浓度的SFE处理细胞，并研究细胞活力、形态、细胞内活性氧（ROS）、迁移以及不同信号蛋白的表达。结果表明，SFE以剂量依赖的方式降低AGS细胞活力并诱导凋亡。细胞内ROS的产生、剂量和时间依赖性的Bax/Bcl2改变以及细胞色素c、半胱天冬酶-3（Casp-3）、半胱天冬酶-8（Casp-8）和聚（ADP-核糖）聚合酶-1（PARP-1）等信号蛋白的高表达证明了SFE在AGS细胞中诱导的凋亡途径。此外，SFE诱导的凋亡还伴随着丝裂原活化蛋白激酶（MAPK）如JNK和P-38的磷酸化。此外，在无毒浓度下剂量依赖性的表皮生长因子受体（EGFR）、磷酸化细胞外信号调节激酶1/2（p-ERK1/2）下调以及细胞迁移抑制证实了SFE在AGS细胞迁移抑制中的活性。因此，本研究证明了SFE通过诱导凋亡以及抑制迁移对人胃癌治疗具有有效的化疗潜力及其初步机制。
