© 1999 Oxford University Press
Article |
Cadmium-induced inhibition of the growth and metastasis of human lung carcinoma xenografts: role of apoptosis
Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences, 111 Alexander Drive, PO Box 12233,
MD F0-09, Research Triangle Park, NC 27709 and
1 Intramural Research Support Program, SAIC Frederick, Frederick, MD 21702, USA
Our previous studies indicate that cadmium in mice can inhibit the formation of chemically induced and spontaneously occurring tumors in the liver and lung. Cadmium is an effective anti-tumor agent when given at non-toxic doses and even when given well after tumor formation, implying a unique sensitivity in certain tumor cells. The present studies tested the ability of cadmium to inhibit growth and progression of transplanted human pulmonary tumor xenografts. Male athymic nude mice were inoculated with either H460 cells, originally derived from a non-small cell pulmonary carcinoma, or DMS 114 cells, originally derived from a small cell lung carcinoma, under the left renal capsule. Starting 1 week later mice received 0, 125 or 250 p.p.m. cadmium in the drinking water, levels without effect on host animal growth or survival, and were observed over the next 4 weeks (H460 cells) or 100 days (DMS 114 cells). An additional experiment gave cadmium as an i.v. loading dose (20 µmol/kg) 4 days after renal inoculation with H460 cells and 200 p.p.m. cadmium in the drinking water from 7 days onward, with an observation period of 28 days. Cadmium caused dose-related reductions in the growth of tumors resulting from the inoculation of either H460 or DMS 114 cells of up to 83%. Additionally, cadmium reduced the rate of tumor metastasis to the lung by up to 58%. Cadmium treatment had no effects on either Bcl-2 or Bax protein expression in tumor xenografts, indicating that apoptotic pathways probably do not contribute to this anti-neoplastic effect. These studies show cadmium can effectively reduce growth and progression of human lung carcinoma xenografts in a fashion that is probably independent of apoptosis.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. Shimoda, T. Nagamine, H. Takagi, M. Mori, and M. P. Waalkes Induction of Apoptosis in Cells by Cadmium: Quantitative Negative Correlation between Basal or Induced Metallothionein Concentration and Apoptotic Rate Toxicol. Sci., December 1, 2001; 64(2): 208 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-M. Chuang, I-C. Wang, and J.-L. Yang Roles of JNK, p38 and ERK mitogen-activated protein kinases in the growth inhibition and apoptosis induced by cadmium Carcinogenesis, July 1, 2000; 21(7): 1423 - 1432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Habeebu, J. Liu, Y. Liu, and C. D. Klaassen Metallothionein-Null Mice Are More Sensitive than Wild-Type Mice to Liver Injury Induced by Repeated Exposure to Cadmium Toxicol. Sci., May 1, 2000; 55(1): 223 - 232. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Meplan, K. Mann, and P. Hainaut Cadmium Induces Conformational Modifications of Wild-type p53 and Suppresses p53 Response to DNA Damage in Cultured Cells J. Biol. Chem., October 29, 1999; 274(44): 31663 - 31670. [Abstract] [Full Text] [PDF]
|
|