Eisa Nada H, ElSherbiny Nehal M, Shebl Abdelhadi M, Eissa Laila A, El-Shishtawy Mamdouh M
Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt.
Cell Biochem Funct. 2015 Dec;33(8):541-51. doi: 10.1002/cbf.3153. Epub 2015 Nov 8.
The present study aims to investigate the in vivo and in vitro anti-tumour properties of phenethyl isothiocyanate (PEITC) alone and in combination with doxorubicin (Dox). The anti-tumour activity was evaluated in vitro by MTT assay using cultured human breast cancer cell line (MCF-7) and human hepatoma cell line (HepG-2) cell lines. In vivo, Ehrlich solid tumour model was used. Tumour volume, weight and antioxidant parameters were determined. Immunohistochemistry analysis for active (cleaved) caspase-3 was also performed. We tested the effect of PEITC treatment on pAkt/Akt ratio, NF-κB p65 DNA binding activity and caspase-9 enzyme activity in both MCF-7 and HepG-2 cell lines. Effect of PEITC treatment on cell migration was assessed by wound healing assay. PEITC and/or Dox treatment significantly inhibited solid tumour volume and tumour weight when compared with control mice. PEITC treatment significantly reduced oxidative stress caused by Dox treatment as indicated by significant increase in total antioxidant capacity and decrease in malondialdehyde level. Microscopic examination of tumour tissues showed a significant increase in active (cleaved) caspase-3 expression in PEITC and/or Dox treated groups. PEITC showed a dose-dependent inhibition of MCF-7 and HepG-2 cellular viability. PEITC inhibited Akt and NF-κB activation and increased caspase-9 activity in a dose-dependent manner. PEITC treatment effectively inhibited both MCF-7 and HepG-2 cell migration. We can conclude that PEITC acts via multiple molecular targets to elicit anti-carcinogenic activity. PEITC/Dox combination therapy might be a potential novel strategy, which may benefit patients with breast and liver cancers.
本研究旨在调查异硫氰酸苯乙酯（PEITC）单独及与阿霉素（Dox）联合使用时的体内外抗肿瘤特性。使用培养的人乳腺癌细胞系（MCF-7）和人肝癌细胞系（HepG-2），通过MTT法在体外评估抗肿瘤活性。在体内，使用艾氏实体瘤模型。测定肿瘤体积、重量和抗氧化参数。还进行了活性（裂解）半胱天冬酶-3的免疫组织化学分析。我们测试了PEITC处理对MCF-7和HepG-2细胞系中pAkt/Akt比值、NF-κB p65 DNA结合活性和半胱天冬酶-9酶活性的影响。通过伤口愈合试验评估PEITC处理对细胞迁移的影响。与对照小鼠相比，PEITC和/或Dox处理显著抑制实体瘤体积和肿瘤重量。总抗氧化能力显著增加和丙二醛水平降低表明，PEITC处理显著降低了Dox处理引起的氧化应激。肿瘤组织的显微镜检查显示，PEITC和/或Dox处理组中活性（裂解）半胱天冬酶-3表达显著增加。PEITC对MCF-7和HepG-2细胞活力表现出剂量依赖性抑制。PEITC以剂量依赖性方式抑制Akt和NF-κB激活并增加半胱天冬酶-9活性。PEITC处理有效抑制了MCF-7和HepG-2细胞迁移。我们可以得出结论，PEITC通过多个分子靶点发挥作用以引发抗癌活性。PEITC/Dox联合疗法可能是一种潜在的新策略，可能使乳腺癌和肝癌患者受益。
