Can melatonin prevent onset breast cancer in mouse xenograft model – Prof Engelbrecht
Prof Anna-Mart Engelbrecht
Title of the project
Can melatonin prevent onset breast cancer in mouse xenograft model?
Breast cancer continues to be a major problem for women worldwide. There is a need to identify and take steps to alter modifiable breast cancer risks. Conditions such as obesity and overweight are risk factors that have reached epidemic proportions. Obesity has been suggested as a most convincing risk factor for the development of breast and colon cancer. Furthermore, adipocytes, which had been considered as an inert storage organ, are receiving attention as a center of metabolic integration. It is clear from existing evidence that adipocytes induce metabolic stress in coordination with immune cells which may explain accelerated cell growth and survival of cancer cells. Since limited progress have been made to change the lifestyle and diet behavior of obese and overweight persons, there is a great need for other preventative measures to combat breast cancer. Several decades of observational data have accumulated to implicate a potential role for melatonin in the prevention of cancer. It was shown in experimental studies that the antineoplastic action of melatonin arises through many different mechanisms, which include its antioxidant, antimitotic and antiangiogenic activity as well as its ability to modulate the immune system and alter fat metabolism. Evidence for the relationship between melatonin production and cancer risk is accumulating from several recent case-control studies and is further supported by indirect evidence from observational studies of night workers, in whom a higher breast and endometrial cancer risk has been described. Of relevance to breast cancer risk, is the fact that melatonin may also block the estrogen receptor, ERa, and have in impact on the enzyme aromatase, which produces estradiol. Aromatase overexpression is a critical factor and the use of aromatase inhibitors is clearly therapeutic in breast cancer. Although the antineoplastic activity of melatonin has been described in several in vitro and observational studies, no knowledge exists regarding the preventative effect of melatonin in a xenograft mouse model (with an uncompromised immune system) where breast cancer is induced. The xenograft mouse model which is established in our lab will also serve as an ideal model to detect early markers of cancer. Therefore, the aims of this study are two-fold: (1) to determine if melatonin has an anti-neoplastic effect in the xenograft mouse model; and (2) to detect early markers of cancer in our model.
To do a large study of this nature, it is very important to use relevant concentrations of melatonin in cell culture experiments, therefore it is essential to start such a study with proper concentration curves. Interestingly, 100 mM of melatonin significantly decreased cell viability in the cancer cell (MCF7 cells), while having an insignificant effect on normal breast epithelial cells (MCF12A cells).