Yamamoto D, Kiyozuka Y, Uemura Y, Yamamoto C, Takemoto H, Hirata H, Tanaka K, Hioki K, Tsubura A
Department of Pathology II, Kansai Medical University, Moriguchi, Osaka, Japan.
J Cancer Res Clin Oncol. 2000 Apr;126(4):191-7. doi: 10.1007/s004320050032.
The effect of cycloprodigiosin hydrochloride (cPrG.HCl), a H+/Cl- symporter, on five human breast cancer cell lines (KPL-1, T-47D, MCF-7, MKL-F, and MDA-MB-231), a human breast epithelial cell line (HBL-100), and a human fibroblast cell line (WI-38-40) was examined. cPrG.HCl inhibited the growth of all five breast cancer cell lines (IC50: 0.46-0.62 microM) and slightly inhibited HBL-100 and WI-38-40 cell growth (IC50: 1.75 microM and 2.26 microM respectively). cPrG.HCl treatment in KPL-1 cells increased the pH of acidic organelles, decreased intracellular pH, and caused apoptosis, which was confirmed by the appearance of a sub-G1 population by flow cytometry and DNA fragmentation. In addition, cPrG.HCl-induced apoptosis was strongly suppressed by imidazole, a cell-permeable base, suggesting that intracellular acidification was essential for the apoptosis. Further, cPrG.HCl treatment up-regulated Bax and Bak expression, down-regulated Bcl-2 expression, and activated caspase-3. Therefore, the intracellular acidification by cPrG.HCl treatment suppressed the growth of human breast cancer cell lines by inducing apoptosis.
研究了盐酸环丙基灵（cPrG.HCl），一种H⁺/Cl⁻共转运体，对五种人乳腺癌细胞系（KPL-1、T-47D、MCF-7、MKL-F和MDA-MB-231）、一种人乳腺上皮细胞系（HBL-100）和一种人成纤维细胞系（WI-38-40）的影响。cPrG.HCl抑制了所有五种乳腺癌细胞系的生长（IC50：0.46 - 0.62微摩尔），并轻微抑制了HBL-100和WI-38-40细胞的生长（IC50分别为1.75微摩尔和2.26微摩尔）。在KPL-1细胞中进行cPrG.HCl处理可提高酸性细胞器的pH值，降低细胞内pH值，并导致细胞凋亡，这通过流式细胞术检测到亚G1期细胞群的出现和DNA片段化得到证实。此外，细胞可渗透碱咪唑强烈抑制了cPrG.HCl诱导的细胞凋亡，表明细胞内酸化对于细胞凋亡至关重要。此外，cPrG.HCl处理上调了Bax和Bak的表达，下调了Bcl-2的表达，并激活了caspase-3。因此，cPrG.HCl处理引起的细胞内酸化通过诱导细胞凋亡抑制了人乳腺癌细胞系的生长。
