Combination of Oral Vitamin D3 with Photodynamic Therapy Enhances Tumor Cell Death in a Murine Model of Cutaneous Squamous Cell Carcinoma. (26th May 2014)

• Record Type: Journal Article
• Authors: Anand, Sanjay; Rollakanti, Kishore R.; Horst, Ronald L.; Hasan, Tayyaba; Maytin, Edward V.
• Is Part Of: Photochemistry and photobiology. Volume 90:Number 5(2014:Sep./Oct.)
• Page Start: 1126
• Page End: 1135
• Publication Date: 2014-05-26
• Subjects: Photochemistry -- Periodicals; Light -- Physiological effect -- Periodicals; 541.35
• DOI: 10.1111/php.12286
• Languages: English
• ISSNs: 0031-8655

Abstract

<abstract abstract-type="main" id="php12286-abs-0001"> <title>Abstract</title> <p>Photodynamic therapy (PDT), in which 5‐ALA (a precursor for protoporphyrin IX, PpIX) is administered prior to exposure to light, is a nonscarring treatment for skin cancers. However, for deep tumors, ALA‐PDT is not always effective due to inadequate production of PpIX. We previously developed and reported a combination approach in which the active form of vitamin D₃ (calcitriol) is given systemically prior to PDT to improve PpIX accumulation and to enhance PDT‐induced tumor cell death; calcitriol, however, poses a risk of hypercalcemia. Here, we tested a possible strategy to circumvent the problem of hypercalcemia by substituting natural dietary vitamin D₃ (cholecalciferol; D₃) for calcitriol. Oral D₃ supplementation (10 days of a 10‐fold elevated D₃ diet) enhanced PpIX levels 3‐ to 4‐fold, and PDT‐mediated cell death 20‐fold, in subcutaneous A431 tumors. PpIX levels and cell viability in normal tissues were not affected. Hydroxylated metabolic forms of D₃ were only modestly elevated in serum, indicating minimal hypercalcemic risk. These results show that brief oral administration of cholecalciferol can serve as a safe neoadjuvant to ALA‐PDT. We suggest a clinical study, using oral vitamin D₃ prior to PDT, should be considered to evaluate this promising new approach to treating human skin cancer.</p> </abstract>