Induction of Apoptosis in Cells by Cadmium: Quantitative Negative Correlation between Basal or Induced Metallothionein Concentration and Apoptotic Rate

Abstract

Metallothionein (MT) often reduces the adverse effects of cadmium (Cd), but how it may alter Cd-induced apoptosis is unclear. The goal of this study was to define the role of MT in Cd-induced apoptosis using cell lines with widely varying sensitivity to Cd. Effects of Cd on growth of human hepatocellular carcinoma cell lines (HepG2 and PLC/PRF/5) were investigated and compared with Chang cells. These cells were cultured with 0, 5, 10, 20, 40, 80, and 120 microM of Cd for 3, 6, 12, and 24 h. Significant cytolethality was observed in HepG2 and PLC/PRF/5 cells in a time- and concentration-dependent manner, with LC(50) values of 24 microM and 13 microM, respectively. However, Chang cells were much less sensitive to Cd-induced cytotoxicity (LC(50), 64 microM). Apoptotic cell death occurring at cytolethal concentrations was demonstrated in all cell lines by DNA fragmentation on agarose gel electrophoresis or by ELISA. When MT was measured, there was a highly significant negative linear correlation between the basal cellular MT concentration or Cd-induced MT and the rate of apoptosis induced by Cd in these cell lines. Treating HepG2 cells with zinc (Zn) made the relatively sensitive HepG2 cell line resistant to Cd-induced apoptosis, likely due to Zn-induced MT. In fact, there was also a significant negative linear correlation between the amount of Zn-induced MT in HepG2 cells and the rate of Cd-induced apoptosis. These findings revealed that basal or induced MT perturbs Cd-induced apoptotic cell death in various cell lines, and a strong negative correlation exists between cellular MT content and the rate of apoptosis induced by Cd.

Transcriptome Analysis in Response to Heat Shock and Cadmium in the Aquatic Fungus Blastocladiella emersonii

“…The gene encoding one of these metacaspases is also among those with the highest number of ESTs sequenced from B. emersonii stress libraries (Table 2). In human cells cadmium is able to induce apoptosis through the activation of caspases by increasing the production of reactive oxygen species and the modulation of protein kinase and phosphatase activities (6,42,53). Caspases are cysteine-proteases essential for the process of apoptosis and are divided into two families: metacaspases, which are found in plants, fungi, and protozoa, and paracaspases, which are observed in metazoa and Dictyostelium discoideum (59).…”

Validation of Atomic Absorption Spectrophotometry and Mercury Analyzer for Analysis of Cadmium, Lead and Mercury in Red Chili Pepper

“…Agric. Res., 10 (1): 65-71, 2016 that Cd acts on the different molecular targets in human organism (Shimoda et al, 2001;Ivanoviene et al, 2004). Lead can accumulate in aquatic biomass and then is concentrated and passed up the food chain to human consumers.…”

Cell specific stress responses of cadmium-induced cytotoxicity

“…Cadmium can act as a mitogen as well as a toxicant depending on the duration of the exposure (Von Zglinicki et al 1992;Habeebu et al 1998;Shimoda et al 2001). Long-term exposure to low doses of cadmium can transform normal cells into malignant cells.…”