Features Partner Sites Information LinkXpress
Sign In
Demo Company

Underlying Mechanism Identified for Prostate Cancer Caused by Cadmium

By BiotechDaily International staff writers
Posted on 18 Apr 2012
Print article
The widespread, extremely toxic heavy metal cadmium, classified as a Group 1 human carcinogen by the International Agency for Research on Cancer and the US National Toxicology Program, has now been shown to induce apoptosis resistance related to carcinogenesis in human prostrate cells.

An established lung carcinogen in humans, cadmium has also been suspected of playing a role in the induction and the development of prostate cancer, one of the most commonly diagnosed cancers in men. Though multiple molecular targets have been identified, which suggests that more than a single pathway may be involved, specific molecular events of the underlying mechanism(s) have remained elusive. It has been hypothesized that a key factor in cadmium-induced malignant transformation is acquisition of apoptotic resistance. In the present study, published online March 20, 2012, in the journal PLoS ONE, scientists investigated cultured cells derived from human prostate epithelium for effects of cadmium exposure on apoptosis and on the expression of some tumor suppressor proteins.

Initially, the normal RWPE-1 cell line was tested and compared with the response of its cadmium-transformed derivative CTPE. Subsequently, different prostate cancer cell lines were analyzed, including primary adenocarcinoma (22Rv1 and CWR-R1) and metastatic adenocarcinoma cells (LNCaP, PC-3, and DU145). Cells were treated for 24 hours with different concentrations of CdCl(2) , upon which apoptosis, cell cycle distribution, and expression of tumor suppressor proteins were analyzed. Concentrations relevant to human exposure were used: cadmium concentrations (10-30 µM) that are within the range that have been found in normal, hypertrophic, and malignant human prostate tissues and that, at the same time, are able to trigger apoptosis in cell culture systems.

Cellular response to cadmium was also evaluated after siRNA-mediated p53 silencing in wild type p53-expressing RWPE-1 and LNCaP cells, and after adenoviral p53 overexpression in p53-deficient DU145 and PC-3 cell lines. These and additional data showed that p53 silencing was able to suppress cadmium-induced apoptosis. The results demonstrated that cadmium can induce p53-dependent apoptosis in human prostate epithelial cells and suggest p53 mutation as a possible contributing factor for the acquisition of apoptotic resistance in cadmium prostatic carcinogenesis.

“In our study, we investigated the effects of cadmium exposure in normal and in tumor cells derived from human prostate tissue,” said Dr. Pier Paolo Claudio, lead scientist of the study and associate professor in the Biomedical Sciences Graduate Program and Department of Biochemistry and Microbiology in the Joan C. Edwards School of Medicine at Marshall University (Huntington, WV, USA). “The focus of work in our laboratory is to understand the molecular mechanisms governing malignant transformation in order to tailor novel therapeutic strategies. To effectively design novel biological drugs, a thorough understanding of the mechanism of cancer pathogenesis is required,” he added.

The authors, part of a collaborative effort between multiple institutions in Italy and the USA, noted that since the acquisition of apoptotic resistance appears to be crucial in cadmium-induced malignant transformation, further characterization of the pathways involved as well as a thorough comparative proteome analysis of the different prostate epithelial cells studied would significantly improve understanding of cadmium carcinogenesis in the prostate.

Related Links:

Marshall University

Print article



view channel
Image: Left: Green actin fibers create architecture of the cell. Right: With cytochalasin D added, actin fibers disband and reform in the nuclei (Photo courtesy of the University of North Carolina).

Actin in the Nucleus Triggers a Process That Directs Stem Cells to Mature into Bone

A team of cell biologists has discovered why treatment of mesenchymal stem cells (MSCs) with the mycotoxin cytochalasin D directs them to mature into bone cells (osteoblasts) rather than into fat cells... Read more


view channel

Molecular Light Shed on “Dark” Cellular Receptors

Scientists have created a new research tool to help find homes for orphan cell-surface receptors, toward better understanding of cell signaling, developing new therapeutics, and determining causes of drug side-effects. The approach may be broadly useful for discovering interactions of orphan receptors with endogenous, naturally... Read more

Lab Technologies

view channel
Image: The new ambr 15 fermentation micro-bioreactor system was designed to enhance microbial strain screening applications (Photo courtesy of Sartorius Stedim Biotech).

New Bioreactor System Streamlines Strain Screening and Culture

Biotechnology laboratories working with bacterial cultures will benefit from a new automated micro bioreactor system that was designed to enhance microbial strain screening processes. The Sartorius... Read more


view channel

Purchase of Biopharmaceutical Company Will Boost Development of Nitroxyl-Based Cardiovascular Disease Drugs

A major international biopharmaceutical company has announced the acquisition of a private biotech company that specializes in the development of drugs for treatment of cardiovascular disease. Bristol-Myers Squibb Co. (New York, NY, USA) has initiated the process to buy Cardioxyl Pharmaceuticals Inc. (Chapel Hill, NC, USA).... Read more
Copyright © 2000-2015 Globetech Media. All rights reserved.