Exposure to cadmium and copper triggers cytotoxic effects and epigenetic changes in human colorectal carcinoma HT‑29 cells

Iftode, Andrada; Drăghici, George Andrei; Macaşoi, Ioana; Marcovici, Iasmina; Coricovac, Dorina; Drăgoi, Răzvan; Tischer, Alina Andreea; Kovatsi, Leda; Tsatsakis, Aristidis; Creţu, Octavian; Dehelean, Cristina

doi:10.3892/etm.2020.9532

Cited by 14 publications

(7 citation statements)

References 57 publications

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“…This phenomenon is common for metallo-chemotherapy agents. For example, arsenic is a well-known human carcinogen, but it is also effective against hematological malignancies and certain solid tumors with arsenic-metal complexes ( 27 ), and the toxic effects of Cd towards colorectal carcinoma cells ( 28 ) might contribute to the antitumor effects of Cd. The use of a toxic metal/metalloid to treat chemo-resistant malignancies could be a strategy in metallo-chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Antitumor effects of cadmium against diethylnitrosamine‑induced liver tumors in mice

Nie

Huang

et al. 2021

Oncol Lett

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Cadmium (Cd) has been reported to exhibit antitumor effects against chemically induced liver tumors. However, the antitumor effects of Cd are not completely understood. Metallotherapy, the use of a toxic metal to attack liver tumors, could be a viable strategy. In the present study, 8-week old, male, C57BL/6 mice were administered injections of diethylnitrosamine (DEN) (90 mg/kg, and then 50 mg/kg 2 weeks later), followed by liver tumor promotion with carbon tetrachloride. Cadmium chloride was administered in the drinking water (1000 ppm) from 21–40 weeks after DEN initiation. Body weights were recorded and liver tumor formation was monitored via ultrasound. At the end of experiments, livers were removed, weighed, and the tumor incidence, tumor numbers and tumor size scores were recorded. Liver histology and metallothionein (MT) immunostaining were performed. After DEN injection, animal body weight decreased, and then slowly recovered with time. Cd treatment did not affect animal body weight gain. Ultrasound analysis detected liver tumors 35 weeks after DEN injection, and the mice were necropsied at 40 weeks. Liver/body weight ratios increased in the DEN and DEN + Cd groups. Cd treatment decreased the tumor incidence (71 vs. 17%), tumor numbers (15 vs. 2) and tumor scores (22 vs. 3) when compared with the DEN only group. Histopathology showed hepatocyte degeneration in all groups, and immunohistochemistry showed MT-deficiency in the liver tumors, while MT staining was intensified in the surrounding tissues. Reverse transcription-quantitative PCR showed increases in α-fetoprotein level in DEN-treated livers, and increases in MT-2 and tumor necrosis factor α (TNFα) levels in Cd-treated livers. Thus, it was concluded that Cd is effective in the suppression of DEN-induced liver tumors, and that the mechanisms may be related to MT-deficiency in tumors and the induction of TNFα to kill tumor cells.

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Section: Discussionmentioning

confidence: 99%

Antitumor effects of cadmium against diethylnitrosamine‑induced liver tumors in mice

Nie

Huang

et al. 2021

Oncol Lett

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“…In another study, the findings have been confirmed in human prostate epithelial cells and embryo lung fibroblasts [52] . Cadmium was also characterized as a hypomethylating agent when it was observed that increased DNMT expression occurred in HT-29 cells after 24-hour exposure to cadmium chloride solution [63] . A study examining the effects of cadmium exposure on histone modifications concluded that the exposure to cadmium alone did not cause increased histone modification.…”

Section: Metalsmentioning

confidence: 99%

Epigenetic mechanisms in metal carcinogenesis

et al. 2022

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“…After this interval, the absorbents were determined spectrophotometrically at 570 and 600 nM using the xMark ™ Microplate spectrophotometer (Bio-Rad). Results expressed as percentages of viable cells (%) were calculated using the formula described in one of our previous studies [79].…”

Section: Cell Viability Assessmentmentioning

confidence: 99%

Comparative Evaluation of the Potential Antitumor of Helleborus purpurascens in Skin and Breast Cancer

Pilut

Manea

Macaşoi

et al. 2022

Plants

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In the field of oncology, the plant kingdom has an inexhaustible supply of bioactive compounds. Phytochemical compounds isolated from Helleborus species have been found to be useful in various chronic diseases. This has brought Helleborus to the attention of medical researchers. H. purpurascens is a plant characteristic of the Carpathian area, known since ancient times for its beneficial effects. The aim of the study was to evaluate the flavonoids composition of a hydroalcoholic extract of H. purpurascens, as well as to assess its antioxidant activity and antitumor potential at the level of two healthy cell lines and four tumor cell lines. In addition, the expression of the genes involved in the apoptotic process (Bcl-2, Bad, and Bax) were evaluated. The results indicated that the extract has a high concentration of flavonoids, such as epicatechin, quercetin, and kaempferol. The extract has an increased antioxidant activity, very similar to that of the standard, ascorbic acid and cytotoxic effects predominantly in the breast cancer cell line, being free of cytotoxic effects in healthy cell lines. Underlying the cytotoxic effect is the induction of the process of apoptosis, which in the present study was highlighted by decreasing the expression of anti-apoptotic genes (Bcl-2) and increasing the expression of pro-apoptotic genes (Bad and Bax). In conclusion, the hydroalcoholic extract of H. purpurascens can be considered an important source for future medical applications in cancer therapy.

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Exposure to cadmium and copper triggers cytotoxic effects and epigenetic changes in human colorectal carcinoma HT‑29 cells

Cited by 14 publications

References 57 publications

Antitumor effects of cadmium against diethylnitrosamine‑induced liver tumors in mice

Antitumor effects of cadmium against diethylnitrosamine‑induced liver tumors in mice

Epigenetic mechanisms in metal carcinogenesis

Comparative Evaluation of the Potential Antitumor of Helleborus purpurascens in Skin and Breast Cancer

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