Studies show that activated vitamin D3 inhibits arsenic-induced carcinogenesis in certain skin cells

According to recent estimates, more than 140 million people in 50 countries are regularly exposed to arsenic through drinking water. The exposure level is well above the guideline value set by the World Health Organization (10 μg/L). Chronic exposure to arsenic from drinking water has been shown to cause various forms of cancer, including skin cancer. Unfortunately, there is a general lack of data on the underlying biological mechanisms governing arsenic-induced carcinogenesis. In addition, methods for the prevention and treatment of arsenic-induced carcinogenesis have so far been elusive.

Scientists from the Shibaura Institute of Technology (SIT) and Nagoya University were recently able to identify the biological mechanisms underlying the inhibition of carcinogenesis. Using in vitro In their research, the research team was able to show how calcitriol, or activated vitamin D3, inhibits arsenic-induced carcinogenesis in a type of skin cell called “keratinocytes.” These cells are mainly found in the epidermis, the outermost layer of the skin. It has been scientifically proven that certain signaling molecules, protein kinases (such as MEK or “AKT”), which control the fate of various biological processes, are strongly associated with tumor development.

Professor Ichiro Yajima from the Division of Molecular and Cellular Toxicology, Department of Biosciences and Engineering, SIT, who led the research team, says: “Our in vitro study with dirty human HaCaT skin keratinocytes showed that calcitriol, also known as activated vitamin D3 or 1,25-dihydroxy-vitamin D3, inhibited anchorage-independent growth induced by arsenic and reduced cancer-related activation.” of several signaling pathways, including MEK, ERK1/2, and AKT, as well as cell cycle activity. »

To clarify the relationship between arsenic uptake and calcitriol treatment, the researchers measured the amount of arsenic in HaCaT cells; long-lived spontaneously immortalized human epidermal keratinocytes; treated with calcitriol using an inductively coupled plasma mass spectrophotometer. Interestingly, arsenic content in HaCaT cells cultured with arsenic was significantly reduced when these cells were treated with increasing doses of calcitriol. The results of their study have been published American Journal of Cancer Research.

Dr. Masashi Kato, professor and co-author of the study at the Department of Occupational and Environmental Health at Nagoya University, Japan, adds: “Calcitriol significantly inhibited arsenic uptake in HaCaT cells by regulating the expression of aquaporin genes (AQP7, 9 and 10) that were modified by arsenic exposure. Vitamin D receptor expression was significantly increased by arsenic exposure, whereas calcitriol had no effect on receptor expression. »

The researchers then sought to understand whether calcitriol inhibited arsenic-induced tumorigenesis in cells other than skin keratinocytes. To this end, they performed anchorage-independent growth assays using a normal human lung epithelial cell line called Beas-2b. The results of these studies were equally striking: arsenic-induced anchorage-independent growth of Beas-2b cells treated with calcitriol was inhibited by 21.4–70.0%, indicating that the potential of calcitriol to inhibit arsenic-induced tumorigenesis is not limited to keratinocytes.

Professor Yajima ponders, “These results show that calcitriol inhibits arsenic-induced tumorigenesis not only in keratinocytes but also in other target cells, including lung epithelial cells.” significantly altered by treatment with calcitriol. Therefore, we believe that activated vitamin D3 or calcitriol may help prevent and treat arsenic-induced diseases, including cancer.

Environmental toxins such as arsenic are major contributors to the development of life-threatening diseases such as cancer. However, it can take years or even decades for cancer to develop from drinking arsenic-contaminated water. Current studies clearly indicate that calcitriol can be used as a test compound to confirm the safety and efficacy of activated vitamin D3 and/or its analogs for the prevention or treatment of arsenic-induced cancer. Early use of vitamin D3 in arsenic-contaminated areas can reduce cancer risk 5 to 10 years later and help people stay healthy long-term. This is really good news for the millions of people forced to survive because of contaminated water around the world.

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