![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
CC Chao, YT Huang, CM Ma, WY Chou and S Lin-Chao
Tumor Biology Laboratory, Department of Biochemistry, Chang Gung Medical College, Taoyuan, Taiwan, Republic of China.
A human colon cancer cell line with acquired multidrug resistance (MDR) was assayed for the intracellular GSH level and the activity of GSH-S- transferase (GST), which catalyzes the conjugation reaction of electrophilic drugs with GSH. The GSH level and GST activity (as measured with 1-chloro-2,4-dinitrobenzene) were elevated in the resistant cells by 1.7-fold and 2-fold, respectively. This elevated catalytic activity of the resistant cells was reflected in a 2-fold increase in GST-pi mRNA, which was not the result of gene amplification. In addition, buthionine sulfoximine, a specific inhibitor of GSH synthesis, significantly increased Adriamycin sensitivity in both the MDR and the parental cells, affecting the former more than the latter. The effects seen with buthionine sulfoximine were not seen with puromycin and actinomycin D. A dramatic overexpression of mdr1, a P-glycoprotein gene responsible for the MDR phenotype, was also observed in the MDR cells. In contrast, none of these products (i.e., mdr P-glycoprotein, GSH level, total GST activity, GST-pi gene copy, and GST-pi mRNA level) was elevated in HeLa cells resistant to cisplatin and some alkylating agents, supporting the notion that the acquisition of cisplatin resistance differs from the mechanism of MDR. These results indicate that the intrinsic GSH level and GST-pi activity affect anthracycline resistance per se and not MDR in the human colon cancer cells.
This article has been cited by other articles:
|
|
 |
|
  M. Monzo, S. Brunet, A. Urbano-Ispizua, A. Navarro, G. Perea, J. Esteve, R. Artells, M. Granell, J. Berlanga, J. M. Ribera, et al. Genomic polymorphisms provide prognostic information in intermediate-risk acute myeloblastic leukemia Blood, June 15, 2006; 107(12): 4871 - 4879. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Lecomte, B. Landi, P. Beaune, P. Laurent-Puig, and M.-A. Loriot Glutathione S-Transferase P1 Polymorphism (Ile105Val) Predicts Cumulative Neuropathy in Patients Receiving Oxaliplatin-Based Chemotherapy. Clin. Cancer Res., May 15, 2006; 12(10): 3050 - 3056. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Stoehlmacher, D. J. Park, W. Zhang, S. Groshen, D. D. Tsao-Wei, M. C. Yu, and H.-J. Lenz Association Between Glutathione S-Transferase P1, T1, and M1 Genetic Polymorphism and Survival of Patients With Metastatic Colorectal Cancer J Natl Cancer Inst, June 19, 2002; 94(12): 936 - 942. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Davies, L. L. Robison, J. D. Buckley, T. Tjoa, W. G. Woods, G. A. Radloff, J. A. Ross, and J. P. Perentesis Glutathione S-Transferase Polymorphisms and Outcome of Chemotherapy in Childhood Acute Myeloid Leukemia J. Clin. Oncol., March 1, 2001; 19(5): 1279 - 1287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Kobayashi, N. Watanabe, N. Yamauchi, N. Tsuji, T. Sato, and Y. Niitsu Endogenous Tumor Necrosis Factor as a Predictor of Doxorubicin Sensitivity in Leukemic Patients Blood, April 1, 1997; 89(7): 2472 - 2479. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
