Chemopreventive and anticancer activities of indomethacin and vitamin D combination on colorectal cancer induced by 1,2‑dimethylhydrazine in rats

Okda,Tarek M.; Abd‑Εlghaffar,Sary K.; Katary,Mohamed A.; Abd‑Αlhaseeb,Mohammad M.

doi:10.3892/br.2020.1403

February-2021 Volume 14 Issue 2

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February-2021 Volume 14 Issue 2

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Article Open Access

Chemopreventive and anticancer activities of indomethacin and vitamin D combination on colorectal cancer induced by 1,2‑dimethylhydrazine in rats

Authors:
- Tarek M. Okda
- Sary K. Abd‑Εlghaffar
- Mohamed A. Katary
- Mohammad M. Abd‑Αlhaseeb
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Affiliations: Department of Biochemistry, Faculty of Pharmacy, Damanhour University, Damanhour, Behira 2251, Egypt, Department of Pathology and Clinical Pathology, Faculty of Veterinary Medicine, Assiut University, Assiut 71515, Egypt, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Damanhour University, Damanhour, Behira 2251, Egypt

Copyright: © Okda et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 27
|
Published online on: December 18, 2020

https://doi.org/10.3892/br.2020.1403
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Abstract

Several studies have revealed that the combination of indomethacin, a nonsteroidal anti‑inflammatory drug (NSAID), and vitamin D reduces the risk of common types of cancers. Nonetheless, research on the deal concentrations used to test the impact of vitamin D on colon cancer is deficient. Along these lines, the aim of the present study was to evaluate the possible role of indomethacin and vitamin D as a preventative as well as a therapeutic operator for colon cancer growth induced by dimethylhydrazine (DMH) in male Albino rats. Fifty male albino rats were utilized in this examination; five groups were assigned from the animals (10 animals each): i) control group considered healthy animals; ii) carcinogen group that received DMH only; iii) prophylactic group; iv) vitamin D and indomethacin‑treated group; and v) 5‑flurouracil (5‑FU) group. Western blot technique was used to determine the expression of carcinoembryonic antigen (CEA) and platelet‑derived growth factor (PDGF). Overexpression of CEA and PDGF was noted in the carcinogenic group, while expression of CEA and PDGF in the prophylactic, vitamin D and indomethacin and 5‑FU groups were markedly reduced. There was a likewise decline in tissue caspase‑3 activity and antioxidant parameters in the carcinogenic group, while, there was an increase in these markers in the 5‑FU group as well as the prophylactic and vitamin D and indomethacin groups. The combination of vitamin D and indomethacin markedly reduced the incidence and severity of colon cancer. The molecular, biochemical and histopathological analysis related with the oral administration of vitamin D and indomethacin display its capacity to limit the frequency of colorectal cancer.

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1	Sung JJY, Chiu HM, Jung KW, Jun JK, Sekiguchi M, Matsuda T and Kyaw MH: Increasing trend in young-onset colorectal cancer in Asia: more cancers in men and more rectal cancers. Am J Gastroenterol. 114:322–329. 2019.PubMed/NCBI View Article : Google Scholar
2	Lofano K, Principi M, Scavo MP, Pricci M, Ierardi E and Di Leo A: Dietary lifestyle and colorectal cancer onset, recurrence, and survival: Myth or reality? J Gastrointest Cancer. 44:1–11. 2013.PubMed/NCBI View Article : Google Scholar
3	Wolpin BM and Mayer RJ: Systemic treatment of colorectal cancer. Gastroenterology. 134:1296–1310. 2008.PubMed/NCBI View Article : Google Scholar
4	Meeker S, Seamons A, Paik J, Treuting PM, Brabb T, Grady WM and Maggio-Price L: Increased dietary vitamin D suppresses MAPK signaling, colitis, and colon cancer. Cancer Res. 74:4398–4408. 2014.PubMed/NCBI View Article : Google Scholar
5	Garland CF and Garland FC: Do sunlight and vitamin D reduce the likelihood of colon cancer? Int J Epidemiol. 9:227–231. 1980.PubMed/NCBI View Article : Google Scholar
6	Deeb KK, Trump DL and Johnson CS: Vitamin D signalling pathways in cancer: Potential for anticancer therapeutics. Nat Rev Cancer. 7:684–700. 2007.PubMed/NCBI View Article : Google Scholar
7	Ng K, Meyerhardt JA, Wu K, Feskanich D, Hollis BW, Giovannucci EL and Fuchs CS: Circulating 25-hydroxyvitamin D levels and survival in patients with colorectal cancer. J Clin Oncol. 26:2984–2991. 2008.PubMed/NCBI View Article : Google Scholar
8	Ananthakrishnan AN, Khalili H, Higuchi LM, Bao Y, Korzenik JR, Giovannucci EL, Richter JM, Fuchs CS and Chan AT: Higher predicted vitamin D status is associated with reduced risk of Crohn's disease. Gastroenterology. 142:482–489. 2012.PubMed/NCBI View Article : Google Scholar
9	Fichera A, Little N, Dougherty U, Mustafi R, Cerda S, Li YC, Delgado J, Arora A, Campbell LK, Joseph L, et al: A vitamin D analogue inhibits colonic carcinogenesis in the AOM/DSS model. J Surg Res. 142:239–245. 2007.PubMed/NCBI View Article : Google Scholar
10	Gorham ED, Garland CF, Garland FC, Grant WB, Mohr SB, Lipkin M, Newmark HL, Giovannucci E, Wei M and Holick MF: Optimal vitamin D status for colorectal cancer prevention: A quantitative meta analysis. Am J Prev Med. 32:210–216. 2007.PubMed/NCBI View Article : Google Scholar
11	Rayyan Y, Williams J and Rigas B: The role of NSAIDs in the prevention of colon cancer. Cancer Invest. 20:1002–1011. 2002.PubMed/NCBI View Article : Google Scholar
12	Rao P and Knaus EE: Evolution of nonsteroidal anti-inflammatory drugs (NSAIDs): Cyclooxygenase (COX) inhibition and beyond. J Pharm Pharm Sci. 11:81s–110s. 2008.PubMed/NCBI View Article : Google Scholar
13	Woo JK, Kang JH, Jang YS, Ro S, Cho JM, Kim HM, Lee SJ and Oh SH: Evaluation of preventive and therapeutic activity of novel non-steroidal anti-inflammatory drug, CG100649, in colon cancer: Increased expression of TNF-related apoptosis-inducing ligand receptors enhance the apoptotic response to combination treatment with TRAIL. Oncol Rep. 33:1947–1955. 2015.PubMed/NCBI View Article : Google Scholar
14	Vane JR and Botting RM: Mechanism of action of anti-inflammatory drugs. Adv Exp Med Biol. 433:131–138. 1997.PubMed/NCBI View Article : Google Scholar
15	Lai SW and Liao KF: Aspirin use after diagnosis improves survival in older adults with colon cancer. J Am Geriatr Soc. 61:843–844. 2013.PubMed/NCBI View Article : Google Scholar
16	Peyre M, Salaud C, Clermont-Taranchon E, Niwa-Kawakita M, Goutagny S, Mawrin C, Giovannini M and Kalamarides M: PDGF activation in PGDS-positive arachnoid cells induces meningioma formation in mice promoting tumor progression in combination with Nf2 and Cdkn2ab loss. Oncotarget. 6:32713–32722. 2015.PubMed/NCBI View Article : Google Scholar
17	Zhou J, Tang ZY, Fan J, Wu ZQ, Li XM, Liu YK, Liu F, Sun HC and Ye SL: Expression of platelet-derived endothelial cell growth factor and vascular endothelial growth factor in hepatocellular carcinoma and portal vein tumor thrombus. J Cancer Res Clin Oncol. 126:57–61. 2000.PubMed/NCBI View Article : Google Scholar
18	Sumiyoshi H and Wargovich MJ: Chemoprevention of 1,2-dimethylhydrazine-induced colon cancer in mice by naturally occurring organosulfur compounds. Cancer Res. 50:5084–5087. 1990.PubMed/NCBI
19	Lappe JM, Travers-Gustafson D, Davies KM, Recker RR and Heaney RP: Vitamin D and calcium supplementation reduces cancer risk: Results of a randomized trial. Am J Clin Nutr. 85:1586–1591. 2007.PubMed/NCBI View Article : Google Scholar
20	Quidville V, Segond N, Pidoux E, Cohen R, Jullienne A and Lausson S: Tumor growth inhibition by indomethacin in a mouse model of human medullary thyroid cancer: Implication of cyclooxygenases and 15-hydroxyprostaglandin dehydrogenase. Endocrinology. 145:2561–2571. 2004.PubMed/NCBI View Article : Google Scholar
21	Gupta S, Khan H, Barik S and Negi MP: Clinical benefits of concurrent capecitabine and cisplatin versus concurrent cisplatin and 5-flurouracil in locally advanced squamous cell head and neck cancer. Drug Discov Ther. 7:36–42. 2013.PubMed/NCBI View Article : Google Scholar
22	Miranda EG, Nascimento VP, Waisberg DR, Sousa MW, Lima MF, Silva DS and Waisberg J: Inhalation anesthesia equipment for rats with provision of simultaneous anesthetic and oxygen. Acta Cir Bras. 26:140–143. 2011.PubMed/NCBI View Article : Google Scholar
23	Buege JA and Aust SD: Microsomal lipid peroxidation. Methods Enzymol. 52:302–310. 1978.PubMed/NCBI View Article : Google Scholar
24	van Bezooijen RL, Que I, Ederveen AG, Kloosterboer HJ, Papapoulos SE and Löwik CW: Plasma nitrate+nitrite levels are regulated by ovarian steroids but do not correlate with trabecular bone mineral density in rats. J Endocrinol. 159:27–34. 1998.PubMed/NCBI View Article : Google Scholar
25	Martin P and Nunan R: Cellular and molecular mechanisms of repair in acute and chronic wound healing. Br J Dermatol. 173:370–378. 2015.PubMed/NCBI View Article : Google Scholar
26	Hull MA, Gardner SH and Hawcroft G: Activity of the non-steroidal anti-inflammatory drug indomethacin against colorectal cancer. Cancer Treat Rev. 29:309–320. 2003.PubMed/NCBI View Article : Google Scholar
27	Feldman D, Krishnan AV, Swami S, Giovannucci E and Feldman BJ: The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer. 14:342–357. 2014.PubMed/NCBI View Article : Google Scholar
28	Welsh J: Cellular and molecular effects of vitamin D on carcinogenesis. Arch Biochem Biophys. 523:107–114. 2012.PubMed/NCBI View Article : Google Scholar
29	Ojima T, Iwahashi M, Nakamura M, Matsuda K, Nakamori M, Ueda K, Naka T, Ishida K, Primus FJ and Yamaue H: Successful cancer vaccine therapy for carcinoembryonic antigen (CEA)-expressing colon cancer using genetically modified dendritic cells that express CEA and T helper-type 1 cytokines in CEA transgenic mice. Int J Cancer. 120:585–593. 2007.PubMed/NCBI View Article : Google Scholar
30	Pan HD, Peng YF, Xiao G and Gu J: High levels of serum platelet-derived growth factor-AA and human epidermal growth factor receptor-2 are predictors of colorectal cancer liver metastasis. World J Gastroenterol. 23:1233–1240. 2017.PubMed/NCBI View Article : Google Scholar
31	Jung MY, Kang HJ and Moon A: Capsaicin-induced apoptosis in SK-Hep-1 hepatocarcinoma cells involves Bcl-2 downregulation and caspase-3 activation. Cancer Lett. 165:139–145. 2001.PubMed/NCBI View Article : Google Scholar
32	Okda TM, Abd-Alhaseeb MM, Barka K and Ragab NM: Ginger potentiates the effects of silymarin on liver fibrosis induced by CCL4: The role of galectin-8. Eur Rev Med Pharmacol Sci. 23:885–891. 2019.PubMed/NCBI View Article : Google Scholar
33	Katary MA, Abdelsayed R, Alhashim A, Abdelhasib M and Elmarakby AA: Salvianolic acid B slows the progression of breast cancer cell growth via enhancement of apoptosis and reduction of oxidative stress, inflammation, and angiogenesis. Int J Mol Sci. 20(5653)2019.PubMed/NCBI View Article : Google Scholar