Cell Proliferation and Tumor Induction by Ochratoxin A in Mouse Skin and Evaluation of Cyclin D1 and Cyclooxygenase-2 Expressions.

Sai Yang,Yajia Wen

doi:10.1155/2021/1723486

Abstract

Motivation. Skin tumor is one of the frequent occurring forms of cancer where 2-3 million instances are reported worldwide. The ultraviolet rays along with the environmental pollutants and other contaminants can be the potential factors of skin cancer. Cyclin D1 is a serious gene included in controlling the development through the G1 phase of the cell cycle. Ochratoxin A (OTA) is a naturally existing mycotoxin which majorly occurs in food like grains. It is responsible for producing the splitting of single-strand DNA and is identified to be cancer-causing. It is established as a critical risk factor towards reproductive health in both males and females. Methodology. A single dose of ochratoxin A was used for topical application for assessment of skin tumor promotion activity, hyperplasia, ornithine decarboxylase activity, and expression of cyclin D1 and COX-2 in mouse skin. Enhancement in the synthesis of DNA, activation of the epidermal growth factor receptor, and overexpression of cyclin D1 and COX-2 were noted. Primary murine keratinocyte cell culture was cultured with Waymouth's medium. Western blot analysis and real-time polymerase chain reaction (RT-PCR) were used to detect the expression of cyclin D1 and COX-2. Chromatin immunoprecipitation (ChIP) assays were used to the association between AP-1 transcription and nuclear factor-kappaB (NF-κB) with COX-2 and cyclin D1 promoters. Results. The results found that cyclin D1 and COX-2 were responsible for stimulating OTA-induced PMK proliferation and hyperplasia. Implications. EGFR-mediated pathways were also responsible for tumor promotion due to OTA.

Highlights

As per the World Health Organization (WHO) analysis, the cases of nonmelanoma skin carcinoma are expanding with approximately 2-3 million fresh diagnosed cases [1]
Ochratoxin A (OTA) is a mycotoxin which is originated from various Aspergillus and Penicillium families, which is a familiar contaminant found in wheat, coffee, spices, etc., and damages human health along with the livestock [3]
ochratoxin A (OTA), TPA (12-Otetradecanoylphorbol-13-acetate), 2-mercaptoethanol, DMBA (7,12-dimethylbenz[α]anthracene), and Tris buffer were obtained from Sigma Aldrich, USA; bovine serum albumin, ethylenediaminetetraacetic acid disodium salt, phenylmethylsulfonyl fluoride, and protease inhibitor cocktail set I were obtained from Thermo Fisher Scientific; anti-β-actin, anticyclin D1, anti-p-NF-κB, anti-c-fos, blotto, anti-cjun, and anti-p-IκBα were obtained from Bioz; anti-pERK1/2, anti-p-EGFR, anti-p-JNK, anti-COX-2, anti-p-Akt, and anti-p-p38 were obtained from Abcam. [3H]-thymidine and [14C]-ornithine were obtained from PerkinElmer

Summary

Introduction

As per the World Health Organization (WHO) analysis, the cases of nonmelanoma skin carcinoma are expanding with approximately 2-3 million fresh diagnosed cases [1]. The ultraviolet (UV) rays from the sun are examined as the primary reason for skin carcinoma; still, the revelation to more possible cancer-causing chemicals which comprise mycotoxins cannot be controlled, and their toxicity needs to be assessed [2]. Ochratoxin A (OTA) is a mycotoxin which is originated from various Aspergillus and Penicillium families, which is a familiar contaminant found in wheat, coffee, spices, etc., and damages human health along with the livestock [3]. Preliminary studies exhibited the kidney as the principal goal organ for ochratoxin A toxicity aside from the evolution of neurons, including the liver as well as the human resistance system [4]. Multiple varieties of fungi from Aspergillus, Penicillium, and Alternaria generate the mycotoxin ochratoxin A [5]

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Results

Conclusion