There is increasing evidence that Vitamin D (Vit D) and its metabolites, besides their well-known calcium-related functions, may also exert antiproliferative, pro-differentiating, and immune modulatory effects on tumor cells in vitro and may also delay tumor growth in vivo. The aim of this review is to provide fresh insight into the most recent advances on the role of Vit D and its analogues as chemopreventive drugs in cancer therapy. A systematic review of experimental and clinical studies on Vit D and cancer was undertaken by using the major electronic health database including ISI Web of Science, Medline, PubMed, Scopus and Google Scholar. Experimental and clinical observations suggest that Vit D and its analogues may be effective in preventing the malignant transformation and/or the progression of various types of human tumors including breast cancer, prostate cancer, colorectal cancer, and some hematological malignances. These findings suggest the possibility of the clinical use of these molecules as novel potential chemopreventive and anticancer agents.

The serum levels of lysosomal cathepsin B and L and Stefin A, an intracellular inhibitor of these proteolytic enzymes, were determined in patients with hepatocellular carcinoma (HCC) and/or liver cirrhosis (LC) and correlated with some clinical and biochemical parameters of these diseases. Cathepsin B serum levels were increased in HCC and in LC patients as compared to normal subjects (p < 0.001). However no difference was observed between HCC and LC groups. Interestingly, a significant relationship was evidenced between cathepsin B serum content and the grade of severity of cirrhosis (r = 0.41; p < 0.001). Cathepsin L was significantly elevated only in sera of cancer patients as compared to normal subjects or LC patients (p < 0.001) and significantly correlated with the number of malignant lesions (r = 0.49; p = 0.001). Stefin A serum levels were increased in HCC and LC patients as compared to healthy subjects (p < 0.02). However, these levels were significantly higher in the LC group as compared to the HCC group (p < 0.05). In cancer patients, a significant relationship was observed between Stefin A serum content and tumor size (r = 0.35; p < 0.05), number of neoplastic lesions (r = 0.556; p < 0.001) and serum a-fetoprotein (r = 0.38; p < 0.01). These data suggest that cathepsin B and L and Stefin A may be potentially useful as additional biochemical parameters to monitor the therapeutic response of these diseases to clinical treatments and to identify patients with cirrhosis developing precancerous lesions.