Sreevalsan Sandeep, Jutooru Indira, Chadalapaka Gayathri, Walker Michael, Safe Stephen
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843-4466, USA.
Int J Oncol. 2009 Nov;35(5):1191-9. doi: 10.3892/ijo_00000436.
1,1-Bis(3'-indolyl)-1-(p-bromophenyl)methane (DIM-C-pPhBr) and the 2,2'-dimethyl analog (2,2'-diMeDIM-C-pPhBr) inhibit proliferation and induce apoptosis in SW480 colon and Panc28 pancreatic cancer cells. In this study, treatment with 10-20 microM concentrations of these compounds for 24 h induced cleaved PARP and decreased survivin protein and mRNA expression in both cell lines. However, results of time course studies show that DIM-C-pPhBr and 2,2'-diMeDIM-C-pPhBr decrease survivin protein within 2 h after treatment, whereas survivin mRNA levels were decreased only at later time-points indicating activation of transcription-independent and -dependent pathways for downregulation of survivin. In addition, we also observed that gamma-radiation inhibited pancreatic and colon cancer cell growth and this was associated with enhanced expression of survivin after 24 (SW480) or 24 and 48 h (Panc28) and correlated with previous studies on the role of survivin in radiation-resistance. However, in cells co-treated with gamma-radiation plus DIM-C-pPhBr or 2,2'-diMeDIM-C-pPhBr, induction of survivin by gamma-radiation was inhibited after co-treatment with both compounds, suggesting applications for these drugs in combination cancer chemotherapy with gamma-radiation.
1,1-双（3'-吲哚基）-1-（对溴苯基）甲烷（DIM-C-pPhBr）及其2,2'-二甲基类似物（2,2'-二甲基-DIM-C-pPhBr）可抑制SW480结肠癌细胞和Panc28胰腺癌细胞的增殖并诱导其凋亡。在本研究中，用10 - 20微摩尔浓度的这些化合物处理24小时，可诱导PARP裂解，并降低这两种细胞系中生存素蛋白和mRNA的表达。然而，时间进程研究结果表明，DIM-C-pPhBr和2,2'-二甲基-DIM-C-pPhBr在处理后2小时内即可降低生存素蛋白水平，而生存素mRNA水平仅在较晚时间点下降，这表明存在转录非依赖性和依赖性途径来下调生存素。此外，我们还观察到γ射线辐射可抑制胰腺和结肠癌细胞的生长，这与24小时（SW480）或24小时及48小时（Panc28）后生存素表达增强有关，且与先前关于生存素在辐射抗性中作用的研究相关。然而，在用γ射线辐射加DIM-C-pPhBr或2,2'-二甲基-DIM-C-pPhBr共同处理的细胞中，γ射线辐射诱导的生存素表达在与这两种化合物共同处理后受到抑制，这表明这些药物在与γ射线辐射联合进行癌症化疗方面具有应用前景。
