Vitamin D signaling regulates oral keratinocyte proliferation in vitro and in vivo

Yuan, Feng-ning Frank; Valiyaparambil, Jayasanker; Woods, Michael C.; Tran, Huy; Pant, Rima; Adams, John S.; Mallya, Sanjay M.

doi:10.3892/ijo.2014.2338

Cited by 23 publications

(13 citation statements)

References 27 publications

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“…In our study, we observed increased VDR staining in carcinogen-exposed tongues compared to naïve tongue tissue. This observation is consistent with a recent report by Yuan et al , in which increased VDR immunoreactivity was seen in human OSCC compared to normal oral mucosa (31). In the same study, increased VDR immunostaining was also observed in murine OSCC lesions compared to normal oral mucosa in mice treated with 4NQO.…”

Section: Discussionsupporting

confidence: 94%

Impact of Short-term 1,25-Dihydroxyvitamin D3 on the Chemopreventive Efficacy of Erlotinib against Oral Cancer

Bothwell

Shaurova

Merzianu³

et al. 2015

Cancer Prevention Research

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Activation of the epidermal growth factor receptor (EGFR) pathway is an early event in head and neck carcinogenesis. As a result, targeting EGFR for chemoprevention of head and neck squamous cell carcinomas (HNSCC) has received considerable attention. In the present study, we examined the impact of 1,25(OH)2D3, the active metabolite of the nutritional supplement vitamin D on the chemopreventive efficacy of the EGFR inhibitor, erlotinib, against HNSCC. Experimental studies were conducted in patient derived xenografts (PDX) and the 4-nitroquinoline-1-oxide (4NQO) carcinogen-induced model of HNSCC. Short-term treatment (4 weeks) of PDX-bearing mice with 1,25(OH)2D3 and erlotinib resulted in significant inhibition of tumor growth. Non-invasive magnetic resonance imaging (MRI) enabled longitudinal monitoring of disease progression in the 4NQO model with 100% of control animals showing evidence of neoplastic lesions by 24 weeks. Among the experimental groups, animals treated with the combination regimen showed the greatest reduction in tumor incidence and volume (p<0.05). Combination treatment was well tolerated and was not associated with any significant change in body weight. Histopathologic assessment revealed a significant reduction in the degree of dysplasia with combination treatment. Immunoblot analysis of whole tongue extracts showed down regulation of phospho-EGFR and phospho-Akt with the combination regimen. These results highlight the potential of 1,25(OH)2D3 to augment the efficacy of erlotinib against HNSCC. Further optimization of schedule and sequence of this combination regimen along with investigation into the activity of less calcemic analogues or dietary vitamin D is essential to fully realize the potential of this approach.

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Section: Discussionsupporting

confidence: 94%

Impact of Short-term 1,25-Dihydroxyvitamin D3 on the Chemopreventive Efficacy of Erlotinib against Oral Cancer

Bothwell

Shaurova

Merzianu³

et al. 2015

Cancer Prevention Research

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“…However, a previous published study by Yuan et al . ( 55 ) strongly supports a crucial role for vitamin D signaling in oral keratinocyte pathophysiology in-vitro and in-vivo but vitamin D deficiency alone seems to be insufficient to alter oral epithelial homeostasis and provoke carcinogenesis. Afzal et al .…”

Section: Discussionmentioning

confidence: 82%

Serum vitamin D levels of patients with oral squamous cell carcinoma (OSCC) and expression of vitamin D receptor in oral precancerous lesions and OSCC

Grimm¹,

Cetindis²,

Biegner³

et al. 2015

Med Oral

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Background: Resistance to programmed cell death (apoptosis) is a crucial factor for the carcinogenesis of oral squamous cell carcinoma (OSCC). Vitamin D (calcitriol) may overcome apoptosis resistance in tumor cells of OSCC. Vitamin D receptor (VDR) expression in oral precancerous lesions of OSCC has not been analyzed and serum vitamin D level seems to be a predictor of cancer development. Material and Methods: Expression of VDR was analyzed in normal oral mucosa (n=5), oral precursor lesions (simple hyperplasia, n=11; squamous intraepithelial neoplasia, SIN I-III, n=35), and OSCC specimen (n=42) by immunohistochemistry (IHC). Moreover, serum vitamin D levels were measured by 25(OH)D3 (calcidiol) in patients with OSCC (n=42) and correlated with IHC results. Results: Expression of VDR was significantly increased in precancerous and OSCC compared with normal tissue. Compared with SIN I-III lesions VDR expression significantly decreased in OSCC. Severe vitamin D deficiency was detected in our OSCC patient cohort but there was no significant correlation analyzed between serum vitamin D levels and corresponding immunohistochemically detected VDR expression in OSCC. Conclusions: Our survey provides the first evidence of VDR expression in precancerous lesions of OSCC. Apoptosis induction of VDR+ cells in oral precancerous lesions and OSCC by natural vitamin D or synthetic vitamin D compounds could be useful for chemoprevention. Moreover, systemically and/or locally applied, these compounds may act as sensitizers for apoptosis mediated by radio-, and chemotherapy treatment in OSCC. Key words:Oral cancer, oral precancer, lichen planus, leukoplakia, apoptosis, serum 25(OH)D3, vitamin D receptor, chemoprevention, multistep carcinogenesis.

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“…Large-scale population studies have revealed the high prevalence of vitamin D deficiency even in sunshine-rich countries such as India [ 21 – 23 ]. Epidemiologic and case-controlled studies have demonstrated that low vitamin D levels are associated with head and neck cancer risk [ 24 , 25 ]. In the present work a large proportion of study subjects across both groups (76.3% of cases and 68.4% of healthy controls) were found to be deficient in vitamin D, with significantly lower mean levels in cases compared to healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Expression of vitamin D receptor and vitamin D status in patients with oral neoplasms and effect of vitamin D supplementation on quality of life in advanced cancer treatment

Anand¹,

Singh²,

Sonkar³

et al. 2017

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Aim of the studyVitamin D receptor (VDR) expression and serum vitamin D scores in oral premalignant lesions and oral cancer have not been widely analyzed. The role of vitamin D supplementation in advanced oral cancer for improving quality of life (QOL) is also a matter of research.Material and methodsVitamin D receptor expression and vitamin D scores were analyzed in normal oral mucosa (n = 95), leukoplakia (n = 23) and oral cancer (n = 87). 45 patients with advanced oral cancer subjected to chemoradiation were evaluated for the effect of vitamin D supplementation on most observable QOL parameters such as oral mucositis, swallowing performance and overall QOL.ResultsVitamin D receptor expression was increased in oral neoplastic lesions. Vitamin D scores were significantly lower in cases compared to healthy controls (p = 0.002). Vitamin D supplementation significantly reduced the therapy-related toxicities in advanced cancer, thus reducing morbidity and improving QOL.ConclusionsVitamin D receptor expression is increased in premalignant lesions and oral cancer. Vitamin D insufficiency and deficiency are prevalent in patients with oral neoplastic lesions. Vitamin D supplementation has a role in reducing treatment-related toxicities, especially in advanced cancer.

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Vitamin D signaling regulates oral keratinocyte proliferation in vitro and in vivo

Cited by 23 publications

References 27 publications

Impact of Short-term 1,25-Dihydroxyvitamin D3 on the Chemopreventive Efficacy of Erlotinib against Oral Cancer

Impact of Short-term 1,25-Dihydroxyvitamin D3 on the Chemopreventive Efficacy of Erlotinib against Oral Cancer

Serum vitamin D levels of patients with oral squamous cell carcinoma (OSCC) and expression of vitamin D receptor in oral precancerous lesions and OSCC

Expression of vitamin D receptor and vitamin D status in patients with oral neoplasms and effect of vitamin D supplementation on quality of life in advanced cancer treatment

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