RETRACTED ARTICLE: Growth inhibition and apoptosis in colorectal cancer cells induced by Vitamin D-Nanoemulsion (NVD): involvement of Wnt/β-catenin and other signal transduction pathways

Abstract

BackgroundMore than the two decades, the question of whether vitamin D has a role in cancer frequency, development, and death has been premeditated in detail. Colorectal, breast, and prostate cancers have been a scrupulous spot of center, altogether, these three malignancies report for approximately 35% of cancer cases and 20% of cancer demises in the United States, and as such are a chief public health apprehension. The aim was to evaluate antitumor activity of Vitamin D-Nanoemulsion (NVD) in colorectal cancer cell lines and HCT116 xenograft model in a comprehensive approach.MethodsTwo human colorectal cancer cell lines HCT116 and HT29 (gained from College of Pharmacy, King Saud University, KSA were grown. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazoliumbromide protocol were performed to show the impact of NVD and β-catenin inhibitor (FH535) on the viability of HCT116 and HT29 cell lines. Apoptosis/cell cycle assay was performed. Analysis was done with a FACScan (Becton–Dickinson, NJ). About 10,000 cells per sample were harvested and Histograms of DNA were analyzed with ModiFitLT software (verity Software House, ME, USA). Western blotting and RT-PCR were performed for protein and gene expression respectively in in vitro and in vivo.ResultsWe found that NVD induced cytotoxicity in colorectal cells in a dose-dependent manner and time dependent approach. Further, our data validated that NVD administration of human colorectal cancer HCT116 and HT29 cells resulted in cell growth arrest, alteration in molecules regulating cell cycle operative in the G2 phase of the cell cycle and apoptosis in a dose dependent approach. Further our results concluded that NVD administration decreases expression of β-catenin gene, AKT gene and Survivin gene and protein expression in in vitro and in vivo.ConclusionOur findings suggest that targeting β-catenin gene may encourage the alterations of cell cycle and cell cycle regulators. Wnt/β-catenin signaling pathway possibly takes part in the genesis and progression of colorectal cancer cells through regulating cell cycle and the expression of cell cycle regulators.Electronic supplementary materialThe online version of this article (10.1186/s13578-019-0277-z) contains supplementary material, which is available to authorized users.

Effects of vitamin D in the nervous system: Special focus on interaction with steroid hormone signalling and a possible role in the treatment of brain cancer

“…A number of findings indicate that 1,25‐dihydroxyvitamin D 3 can stimulate differentiation and suppress proliferation in several cell types . In addition to the suppression of proliferation, 1,25‐dihydroxyvitamin D 3 can also affect viability . The effects may vary in different cells and under different conditions.…”

“…The effects may vary in different cells and under different conditions. Studies examining vitamin D‐dependent responses have, in some cases, indicated a protective role and, in others, a stimulation of apoptosis . However, the reported suppression on proliferation and survival in many cell types has led to an interest in vitamin D administration as a possible treatment to counteract tumour growth or reduce cancer risk …”

“…Vitamin D analogues have been shown to inhibit both cellular growth and viability in various types of cancer cells . So far, relatively few studies have been conducted on tumours of the nervous system .…”

Vitamin D-Induced Molecular Mechanisms to Potentiate Cancer Therapy and to Reverse Drug-Resistance in Cancer Cells

“…Anticancer activity of vitamin D has been largely studied in different types of tumors, elucidating its pivotal role in cancer progression and invasion [ 134 ]. It has been reported that vitamin D inhibits colorectal, prostate and breast cancer cells growth by controlling cell proliferation [ 11 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 ] through cell cycle arrest [ 144 , 147 , 148 , 149 , 150 ], by regulating cell death through apoptosis [ 54 , 144 , 147 , 151 , 152 , 153 ] and autophagic processes [ 154 , 155 ], and by modulating inflammatory processes implicated in immune infiltration and tumor invasiveness [ 134 , 137 , 150 ].…”

Concomitant using of topical carrageenan-kappa and oral vitamin D against 7, 12-dimethylbenz[a]anthracene induced-oral cancer in rats: A synergism or an antagonism effects

“…Vitamin D is a prohormone acts on the nuclear receptor and has pleiotropic effects beyond its nutriceutical actions. Experimental studies carried on the cancer cell lines showed that vitamin D is cytotoxic against cancer cells by inducing apoptosis [17,18]. In human, the vitamin D reduces the risk of cancers and maintains high serum levels of vitamin D in cancer-patients which improve the survival rate [19].…”