A novel chenodeoxycholic derivative HS-1200 enhances radiation-induced apoptosis in MCF-7 cells.
HS-1200, a synthetic chenodeoxycholic acid derivative, has cytotoxic activity in various human cancer cells. The present study was undertaken to examine whether HS-1200 sensitizes radiation-induced apoptosis in MCF-7 human breast carcinoma cells. Clonogenic assay elucidated that the combination treatment with HS-1200 and radiation induced more cytotoxic effects than the radiation treatment alone. Nuclear staining, DNA electrophoresis and Western blot analysis for poly(ADP-ribose) polymerase revealed that the increased cytotoxic effect by the combination treatment resulted from the augmentation of apoptosis. There was an increase in the expression level of Bax and its translocation onto the mitochondria, a reduction in the mitochondrial membrane potential in the earlier time-points, and the release of cytochrome c into the cytosol increased in the MCF-7 cells treated with radiation and HS-1200 compared to the cells treated only with radiation. Therefore, the synthetic bile acid derivative, HS-1200, could have the therapeutic potential as a radiosensitizer in MCF-7 cells.
Yee
Su-Bog
SB
Medical Science Research Center and College of Medicine (BK21 Program), Dong-A University, Busan 602-714, South Korea.
Song
Yeon Suk
YS
Jeong
Seung Hun
SH
Lee
Hyung Sik
HS
Seo
Su Yeong
SY
Kim
Jae Hong
JH
Suh
Hongsuk
H
Kim
Nam Deuk
ND
Yoo
Young Hyun
YH
D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000032:analysis; D001943:Breast Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D049109:Cell Proliferation / Q000187:drug effects; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D003131:Combined Modality Therapy; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000528:radiation effects; D011064:Poly Adenosine Diphosphate Ribose / Q000032:analysis; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D051017:Apoptosis Regulatory Proteins; C479128:HS 1200; D011838:Radiation-Sensitizing Agents; D002635:Chenodeoxycholic Acid; D011064:Poly Adenosine Diphosphate Ribose