Cycloprodigiosin hydrochloride, a H+/Cl- symporter, induces apoptosis in human breast cancer cell lines.
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.
Yamamoto
D
D
Department of Pathology II, Kansai Medical University, Moriguchi, Osaka, Japan.
Kiyozuka
Y
Y
Uemura
Y
Y
Yamamoto
C
C
Takemoto
H
H
Hirata
H
H
Tanaka
K
K
Hioki
K
K
Tsubura
A
A
D017920:Antiporters / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D008565:Membrane Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D025262:Vacuolar Proton-Translocating ATPases; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein
D017920:Antiporters; C494772:BAK1 protein, human; C494826:BAX protein, human; D007166:Immunosuppressive Agents; D007211:Indoles; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011758:Pyrroles; D012333:RNA, Messenger; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; C114260:hydrogen-chloride symporter; C108328:cycloprodigiosin; D025262:Vacuolar Proton-Translocating ATPases; D006180:Proton-Translocating ATPases