A review of molecular events of cadmium-induced carcinogenesis

Abstract

Cadmium (Cd) is a toxic, heavy industrial metal that poses serious environmental health hazards to both humans and wildlife. Recently, Cd and Cd-containing compounds have been classified as known human carcinogens, and epidemiological data show causal associations with prostate, breast, and lung cancer. The molecular mechanisms involved in Cd-induced carcinogenesis are poorly understood and are only now beginning to be elucidated. The effects of chronic exposure to Cd have recently attracted great interest due to the development of malignancies in Cd-induced tumorigenesis in animals models. Briefly, various in vitro studies demonstrate that Cd can act as a mitogen, can stimulate cell proliferation and inhibit apoptosis and DNA repair, and can induce carcinogenesis in several mammalian tissues and organs. Thus, the various mechanisms involved in chronic Cd exposure and malignant transformations warrant further investigation. In this review, we focus on recent evidence of various leading general and tissue-specific molecular mechanisms that follow chronic exposure to Cd in prostate-, breast-, and lung-transformed malignancies. In addition, in this review, we consider less defined mechanisms such as epigenetic modification and autophagy, which are thought to play a role in the development of Cd-induced malignant transformation.

Figure 1. Expression pattern of Cd induced gene expression in prostate, breast and lung cancer

In prostate cancer Cd induced cycle regulatory proteins, pro-surival transcription factors and gene expression in normal prostate epithelial cells. Also, it simultaneously down regulated pro-apoptotic genes such as BAX and caspase 8,6,4,3 in transformed prostate cells. Interestingly, following Cd exposure, prostate and breast cancer share activation of c-myc, c-jun and bcl-2 expression. It also appears that p53 activation is a common event in all three tissue types (prostate, breast and lung) following chronic Cd treatment. Cyclin-D1 expression was found in both breast and lung cancer, however, there is no report in prostate epithelial cells. Similarly, lung and prostate cancer cells shares the common pro-survival gene AKT along with MT following Cd treatment.