Tumor samples from xenograft mice treated with high-dose melatonin exhibited significant downregulation of mRNA gene expression of CA-XII and markedly reduced protein levels of both CA-IX and CA-XII when compared to untreated controls, whereas in vitro results from cultured MDA-MB-231 cancer cells treated with 1 mM melatonin only showed a significant reduction in CA-XII gene expression, with an insignificant difference in protein levels of CA-IX and CA-XII between the melatonin-treated and control groups [495]. Here, CA9 is linked to cancer.