1. Impact of dietary vitamin D on initiation and progression of oral cancer
- Author
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Aparajita Verma, Hendrik DeJong, Mukund Seshadri, Pamela A. Hershberger, and Vui King Vincent-Chong
- Subjects
0301 basic medicine ,Calcitriol ,Carcinogenesis ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Physiology ,medicine.disease_cause ,Biochemistry ,Calcitriol receptor ,Article ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,CYP24A1 ,Vitamin D and neurology ,Animals ,Humans ,Medicine ,Vitamin D ,Vitamin D3 24-Hydroxylase ,Molecular Biology ,Carcinogen ,business.industry ,Body Weight ,Cancer ,Cell Biology ,Vitamin D Deficiency ,medicine.disease ,4-Nitroquinoline-1-oxide ,Disease Models, Animal ,030104 developmental biology ,Dysplasia ,030220 oncology & carcinogenesis ,Dietary Supplements ,Carcinoma, Squamous Cell ,Disease Progression ,Receptors, Calcitriol ,Molecular Medicine ,Mouth Neoplasms ,business ,medicine.drug - Abstract
Calcitriol, the active metabolite of vitamin D, has been widely studied for its preventive and therapeutic activity against several cancers including oral squamous cell carcinoma (OSCC). However, the impact of dietary vitamin D supplementation on initiation and progression of OSCC is unclear. To address this gap in knowledge, we conducted preclinical trials using the 4-nitroquinoline-1-oxide (4NQO) carcinogen model of oral carcinogenesis. Female C57BL/6 mice were maintained on one of three vitamin D diets [ 25 IU, 100 IU, 10,000 IU] and exposed to 4NQO in drinking water for 16 weeks followed by regular water for 10 weeks. Body weight measurements obtained through the study duration did not reveal any differences between the three diets. Animals on 100 IU diet showed lower incidence of high-grade dysplasia/OSCC and higher CD3+ T cells compared to animals on 25 IU and 10000 IU diets. Serum 25(OH)D(3) levels were highest in animals on 10000 IU diet at week 0 (prior to carcinogen exposure) but showed ~50% reduction at week 26. Histologic evaluation revealed highest incidence of OSCC in animals maintained on 10000 IU diet. Animals on 100 IU and 10000 IU diets showed higher vitamin D receptor (VDR) and CYP24A1 immunostaining in high-grade dysplastic lesions and OSCC compared to normal tongue. Validation studies performed in a 4NQO-derived OSCC model showed that short-term treatment of animals on a 25 IU diet with calcitriol significantly inhibited tumor growth compared to controls but did not affect tumor growth in animals on reference diet (1000 IU). Collectively, our results highlight the complex dynamics between vitamin D status and oral carcinogenesis. Our observations also suggest that therapeutic benefits of short-term calcitriol treatment may be more pronounced in vitamin D deficient hosts.
- Published
- 2020
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