Study: Vitamin D3 Reduces Risk of Arsenic-Mediated Skin Cancer

Calcitriol, known as activated vitamin D3, inhibits arsenic-mediated carcinogenesis in certain types of skin cells known as keratinocytes, which are found in the outermost layer of skin, according to the results of an in vitro study conducted by the Shibaura Institute of Technology (SIT) and Nagoya University.

Chronic arsenic exposure from drinking water can cause a variety of cancers, including skin cancer, but there are little data on prevention and treatment of arsenic-mediated carcinogenesis, investigators said.

“Our in vitro study in human nontumorigenic HaCaT skin keratinocytes showed that calcitriol, which is also known as activated vitamin D3 or 1,25-dihydroxy-vitamin D3, inhibited arsenic-mediated anchorage-independent growth with downregulations of cancer-related activation of several signaling pathways, including MEK, ERK1/2, and AKT, as well as activity of cell cycle,” Ichiro Yajima, from the Unit of Molecular and Cellular Toxicology in the Department of Bioscience and Engineering at SIT, said in a statement.

Investigators measured the arsenic levels in HaCaT cells that were treated with calcitriol using a plasma-mass spectrophotometer. They found that the arsenic levels in the HaCaT cells cultured with arsenic decreased when the cells were treated with increasing doses of calcitriol.

Additionally, the investigators looked to see whether calcitriol had an inhibitory effect on arsenic-induced tumorigenesis in cells other than skin keratinocytes. They performed anchorage-independent growth assays using a human normal lung epithelial cell line.

Investigators found that the arsenic-mediated, anchorage-independent growth of the cell line treated with calcitriol was suppressed by about 21.4% to 70%.

This suggests calcitriol has the potential to suppress arsenic-induced tumorigenesis not restricted to keratinocytes, investigators said.

“These results suggest that calcitriol suppresses arsenic-induced tumorigenesis not only in keratinocytes but also in other target cells including lung epithelial cells. Furthermore, the expression pattern of aquaporin genes involved in arsenic uptake, a critical step in arsenic-induced carcinogenesis, is significantly altered by calcitriol treatment,” Yajima said.

“We therefore believe that activated vitamin D3, or calcitriol, may contribute to the prevention and therapy for arsenic-mediated diseases including cancer,” he said.

The study results were published in the American Journal of Cancer Research.

It has been reported that environmental toxins, such as arsenic, can contribute to the development of life-threatening diseases, such as cancer, but it could take years, and in some cases, decades for cancer to develop from drinking arsenic-contaminated water.

Research shows that calcitriol could be used as a test compound for validating the efficacy and safety of activated vitamin D3 and/or in preventing or treating arsenic-triggered cancer, investigators said.

“Calcitriol significantly repressed arsenic uptake in HaCaT cells with the regulation of expressions of aquaporin genes (AQP7, 9, and 10), which were modified by arsenic exposure. Vitamin D receptor expression was significantly increased by arsenic exposure whereas calcitriol had no effect on the expression of the receptor,” Masashi Kato, professor at the Department of Occupational and Environmental Health at Nagoya University, said in the statement.

Reference

Activated vitamin D3 treatment may reduce the risk of arsenic-mediated skin cancer. EurekAlert. News release. December 15, 2022. Accessed December 20, 2022. https://www.eurekalert.org/news-releases/974563