title: Effects of 1,25(OH)₂D₃ on Cancer Cells and Potential Applications in Combination with Established and Putative Anti-Cancer Agents.
abstract: The diverse effects of 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), the bio-active form of vitamin D, on cancer cell metabolism and proliferation has made it an interesting candidate as a supporting therapeutic option in cancer treatment. An important strategy in cancer therapy is the use of combination chemotherapy to overcome drug resistance associated with numerous anti-cancer agents and to provide better means of avoiding undesirable side effects. This complex strategy is widely adopted by oncologists and several established "cocktails" of chemotherapeutics are routinely administered to cancer patients. Among the principles followed in designing such treatment regimens is the use of drugs with different mechanisms of action to overcome the issue of tumor heterogeneity and to evade resistance. In light of the profound and diverse effects of 1,25(OH)₂D₃ reported by in vitro and in vivo studies, we discuss how these effects could support the use of this molecule in combination with "classical" cytotoxic drugs, such as platins and anti-metabolites, for the treatment of solid and hematological tumors. We also examine recent evidence supporting synergistic activities with other promising anti-cancer drug candidates, and postulate mechanisms through which 1,25(OH)₂D₃ may help evade chemoresistance.
authors.affiliation: Institut für Pharmazie und Molekulare Biotechnologie (IPMB), Universität Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany. abu.el.maaty@gmail.com.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Abu El Maaty
authors.affiliation: Institut für Pharmazie und Molekulare Biotechnologie (IPMB), Universität Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany. wolfl@uni-hd.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wölfl
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002117:Calcitriol / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D017671:Platinum Compounds / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000494:pharmacology; D043823:Taxoids / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D017671:Platinum Compounds; D043823:Taxoids; D011505:Protein-Tyrosine Kinases; D002117:Calcitriol
keywords: 1,25-dihydroxyvitamin D3; anti-cancer effects; combination chemotherapy