The role of Adipocytokines, Vitamin D, and C in Colorectal Cancer

Authors

DOI:

https://doi.org/10.21123/bsj.2022.7245

Keywords:

Adipocytokines, Adiponectin, Colorectal cancer, Leptin, Vitamin D, Vitamin C

Abstract

Colorectal cancer is the world's 3rd most frequent malignant neoplasm and the 4th most common cancer in Iraq. Leptin and Adiponectin are two major Adipocytokines produced by adipose cells that have opposite effects on the formation of colorectal tumors. Leptin induces tumor growth and metastasis, whereas Adiponectin inhibits it. 1,25-Dihydroxyvitamin D controls and limits cancer cell proliferation, differentiation, and survival. Vitamin C deficiency, on the other hand, has been regularly detected in cancer tissues and has potent anti-cancer properties. The purpose of this study was to look at the biochemical role of circulatory Adipocytokine levels (Adiponectin and Leptin) as well as the anti-cancer potentials of Vitamin D and C in CRC patients from Iraq. The research looked at confirmed cases of CRC who were seen at Nanakali Hospital for Blood diseases and Cancer in Erbil before their treatment sessions. A total of 35 patients with confirmed CRC cases and 36 healthy participants who were age, gender, and BMI matched were recruited. ELISA technique was used to quantify serum levels of Adiponectin, Leptin, Vitamin D, & C. The results showed a significant increase (P<0.0001) of serum Adiponectin levels (12.06±1.59) in CRC patients relative to the controls (2.05±0.96). On the contrary, the serum Leptin levels (24.09±2.92) were non-significantly lower (P=0.098) in CRC patients in comparison to controls (53.84±1.54). Furthermore, serum Vitamin D (13.14±1.21) and Vitamin C (1.03±0.10) levels in CRC patients were significantly lower (P<0.0001) when compared to controls (24.49±1.47, 5.78±2.16), respectively. The findings in the current study suggest an imperative biochemical role of Adipocytokines (Adiponectin and Leptin) and Adipose tissue dysfunction in the pathogenesis of CRC patients. Furthermore, decreased serum levels of Vitamin D and C reduce their effective anti-cancer effects, allowing Colorectal malignant neoplasms to survive and develop. Thus, the present study findings suggest Adiponectin and Leptin as potent prognostic and risk factors of CRCs. Also, Vitamin D and C deficiencies are the major risk factors among Iraqi CRC patients.

References

Mhaidat NM, Alzoubi KH, Kubas MA, Banihani MN, Hamdan N, Al‑jaberi TM. High levels of Leptin and non‑high molecular weight‑adiponectin in patients with colorectal cancer: Association with chemotherapy and common genetic polymorphisms. Biomed Rep. 2021; 14(1): 13.

Khalil KH, Al-Hassawi B, Abdo J. Correlation of Neuroendocrine Differentiation with Neuroendocrine Cell Hyperplasia and Vascular Endothelial Growth Factor in Colorectal Adenocarcinoma. Baghdad Sci J. 2021; 18(1): 18-27.

El Halabi I, Bejjany R, Nasr R, Mukherji D, Temraz S, Nassar FJ, et al. Ascorbic acid in colon cancer: from the basic to the clinical applications. Int J Mol Sci. 2018; 19(9): 2752.

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: Cancer J Clin. 2021; 71(3): 209-49.

Di Zazzo E, Polito R, Bartollino S, Nigro E, Porcile C, Bianco A, et al. Adiponectin as link factor between adipose tissue and cancer. Int J Mol Sci. 2019; 20(4): 839.

Tojek K, Anaszewicz M, Szukay B, Czerniak B, Socha E, Lis K, et al. Circulating Leptin, adiponectin, and tumor necrosis factor-alpha in patients undergoing surgery due to colorectal cancer. Digestion. 2021; 102(2): 246-55.

Cavagnari MAV, Vidigal VM, Silva TD, Barão K, Forones NM. Adiponectin, vitamin D and nutritional status in patients with advanced colorectal cancer or during follow-up. Arq Gastroenterol. 2019; 56: 172-77.

Al-Maghrabi JA, Qureshi IA, Khabaz MN. Expression of Leptin in colorectal adenocarcinoma showed significant different survival patterns associated with tumor size, lymphovascular invasion, distant metastasis, local recurrence, and relapse of disease in the western province of Saudi Arabia. Medicine. 2018; 97(34): e12052.

Ochs-Balcom HM, Cannioto R, Nie J, Millen AE, Freudenheim JL, Chen Z, et al. Adipokines do not mediate the association of obesity and colorectal adenoma. J Cancer Epidemiol. 2014; 2014: Article ID 371254.

Wei T, Ye P, Peng X, Wu L-L, Yu G-Y. Circulating adiponectin levels in various malignancies: an updated meta-analysis of 107 studies. Oncotarget. 2016; 7(30): 48671–91.

Riondino S, Roselli M, Palmirotta R, Della-Morte D, Ferroni P, Guadagni F. Obesity and colorectal cancer: role of adipokines in tumor initiation and progression. World J Gastroenterol. 2014; 20(18): 5177–90.

Joshi RK, Lee S-A. Obesity related adipokines and colorectal cancer: a review and meta-analysis. Asian Pac J Cancer Prev. 2014; 15(1): 397-405.

Wang Y, Li J, Fu X, Li J, Liu L, Alkohlani A, et al. Association of circulating leptin and adiponectin levels with colorectal cancer risk: A systematic review and meta-analysis of case-control studies. Cancer Epidemiol. 2021; 73: 101958.

Katira A, Tan PH. Evolving role of adiponectin in cancer-controversies and update. Cancer Biol Med. 2016; 13(1): 101–19.

Parida S, Siddharth S, Sharma D. Adiponectin, obesity, and cancer: clash of the bigwigs in health and disease. Int J Mol Sci. 2019; 20(10): 2519.

Lu W, Huang Z, Li N, Liu H. Low circulating total adiponectin, especially its non-high-molecular weight fraction, represents a promising risk factor for colorectal cancer: a meta-analysis. Onco Targets Ther. 2018; 11: 2519–31.

Ashktorab H, Soleimani A, Nichols A, Sodhi K, Laiyemo AO, Nunlee-Bland G, et al. Adiponectin, Leptin, IGF-1, and tumor necrosis factor alpha as potential serum biomarkers for non-invasive diagnosis of colorectal adenoma in African Americans. Front Endocrinol. 2018; 9: 77.

Otani K, Ishihara S, Yamaguchi H, Murono K, Yasuda K, Nishikawa T, et al. Adiponectin and colorectal cancer. Surg Today. 2017; 47(2): 151-58.

Samad N, Rao T. Role of Leptin in cancer-a systematic review. Biomed J Sci Tech Res. 2019; 18(1): 13226-35.

Jiménez-Cortegana C, López-Saavedra A, Sánchez-Jiménez F, Pérez-Pérez A, Castiñeiras J, Virizuela-Echaburu JA, et al. Leptin, both bad and Good actor in cancer. Biomolecules. 2021; 11(6): 913.

Uyar GO, Sanlier N. Association of adipokines and insulin, which have a role in obesity, with colorectal cancer. Eurasian J Med. 2019; 51(2): 191–95.

Bikle DD. Vitamin D Biochemistry and Physiology. In: Liao EP, editor. Extraskeletal Effects of Vitamin D: A Clinical Guide. Cham: Springer International Publishing; 2018. p. 1-40.

Boughanem H, Canudas S, Hernandez-Alonso P, Becerra-Tomás N, Babio N, Salas-Salvadó J, et al. Vitamin D intake and the risk of colorectal cancer: an updated meta-analysis and systematic review of case-control and prospective cohort studies. Cancers. 2021; 13(11): 2814.

Javed M, Althwanay A, Ahsan F, Oliveri F, Goud HK, Mehkari Z, et al. Role of Vitamin D in Colorectal Cancer: A Holistic Approach and Review of the Clinical Utility. Cureus. 2020; 12(9): e10734.

Vissers M, Das AB. Potential mechanisms of action for vitamin C in cancer: reviewing the evidence. Front Physiol. 2018: 809.

Roa FJ, Peña E, Gatica M, Escobar-Acuña K, Saavedra P, Maldonado M, et al. Therapeutic use of vitamin C in cancer: physiological considerations. Front Pharmacol. 2020; 11: 211.

Chen J, Qin F, Li Y, Mo S, Deng K, Huang Y, et al. High-dose vitamin C tends to kill colorectal cancer with high MALAT1 expression. J Oncol. 2020; 2020: Article ID 2621308.

Pires AS, Marques CR, Encarnação JC, Abrantes AM, Marques IA, Laranjo M, et al. Ascorbic acid chemosensitizes colorectal cancer cells and synergistically inhibits tumor growth. Front Physiol. 2018; 9: 911.

Zekri A-RN, Bakr YM, Ezzat MM, Zakaria MSE, Elbaz TM. Circulating levels of adipocytokines as potential biomarkers for early detection of colorectal carcinoma in Egyptian patients. Asian Pac J Cancer Prev. 2015; 16(16): 6923-28.

Chandler PD, Buring JE, Manson JE, Moorthy M, Zhang S, Lee I-M, et al. Association between plasma adiponectin levels and colorectal cancer risk in women. Cancer Causes Control. 2015; 26(7): 1047-52.

Polito R, Nigro E, Fei L, de Magistris L, Monaco ML, D'amico R, et al. Adiponectin is inversely associated with tumour grade in colorectal cancer patients. Anticancer Res. 2020; 40(7): 3751-57.

Yu L-X, Zhou N-N, Liu L-Y, Wang F, Ma Z-B, Li J, et al. Adiponectin receptor 1 (ADIPOR1) rs1342387 polymorphism and risk of cancer: a meta-analysis. Asian Pac J Cancer Prev. 2014; 15(18): 7515-20.

Li C, Quan J, Wei R, Zhao Z, Guan X, Liu Z, et al. Leptin overexpression as a poor prognostic factor for colorectal cancer. Biomed Res Int. 2020; 2020: Article ID 7532514.

Lin T-C, Hsiao M. Leptin and cancer: Updated functional roles in carcinogenesis, therapeutic niches, and developments. Int J Mol Sci. 2021; 22(6): 2870.

Bolukbas FF, Kilic H, Bolukbas C, Gumus M, Horoz M, Turhal NS, et al. Serum leptin concentration and advanced gastrointestinal cancers: a case controlled study. BMC cancer. 2004; 4(1): 1-4.

Sălăgeanu A. Serum levels of adipokines resistin and Leptin in patients with colon cancer. J Med Life. 2010; 3(4): 416–20.

Kumor A, Daniel P, Pietruczuk M, Małecka-Panas E. Serum leptin, adiponectin, and resistin concentration in colorectal adenoma and carcinoma (CC) patients. Int J Colorectal Dis. 2009; 24(3): 275-81.

Tessitore L, Vizio B, Jenkins O, De Stefano I, Ritossa C, Argiles J, et al. Leptin expression in colorectal and breast cancer patients. Int J Mol Med. 2000; 5(4): 421-27.

Woo H-Y, Park H, Ki C-S, Park YL, Bae WG. Relationships among serum leptin, leptin receptor gene polymorphisms, and breast cancer in Korea. Cancer Lett. 2006; 237(1): 137-42.

Wang D, Gao L, Gong K, Chai Q, Wang G. Increased serum leptin level in overweight patients with colon carcinoma: A cross‑sectional and prospective study. Mol Clin Oncol. 2017; 6(1): 75-78.

Cong J-c, Dai X-w, Shen M-y, Wang J-j, Chen C-s, Zhang H, et al. Expression of obesity hormone leptin in human colorectal cancer. Chin J Cancer Res. 2009; 21(2): 142-46.

Hellström L, Wahrenberg H, Hruska K, Reynisdottir S, Arner P. Mechanisms behind gender differences in circulating leptin levels. J Intern Med. 2000; 247(4): 457-62.

Migliaccio S, Di Nisio A, Magno S, Romano F, Barrea L, Colao AM, et al. Vitamin D deficiency: a potential risk factor for cancer in obesity? Int J Obes. 2022; 46: 707–17.

Jeon S-M, Shin E. Exploring vitamin D metabolism and function in cancer. Exp Mol Med. 2018; 50(4): 1-14.

Javed M, Althwanay A, Ahsan F, Oliveri F, Goud HK, Mehkari Z, et al. Role of Vitamin D in Colorectal Cancer: A Holistic Approach and Review of the Clinical Utility. Cureus. 2020; 12(9): e10734-e34.

Ferrer-Mayorga G, Larriba MJ, Crespo P, Muñoz A. Mechanisms of action of vitamin D in colon cancer. J Steroid Biochem Mol Biol. 2019; 185: 1-6.

Farivar S, Amirinejad R, Naghavi gargari B, Hassani SB, Shirvani farsani Z. In Silico Analysis of Regulatory Elements of the Vitamin D Receptor. Baghdad Sci J. 2020; 17(2): 463-70.

Savoie MB, Paciorek A, Zhang L, Van Blarigan EL, Sommovilla N, Abrams D, et al. Vitamin D Levels in Patients with Colorectal Cancer Before and After Treatment Initiation. J Gastrointest Cancer. 2019; 50(4):769-79.

Al-Ghafari AB, Balamash KS, Al Doghaither HA. Relationship between Serum Vitamin D and Calcium Levels and Vitamin D Receptor Gene Polymorphisms in Colorectal Cancer. Biomed Res Int. 2019; 2019: Article ID 8571541.

Bao Y, Li Y, Gong Y, Huang Q, Cai S, Peng J. Vitamin D Status and Survival in Stage II-III Colorectal Cancer. Front Oncol. 2020; 10: Article 581597.

Zhang L, Zou H, Zhao Y, Hu C, Atanda A, Qin X, et al. Association between blood circulating vitamin D and colorectal cancer risk in Asian countries: a systematic review and dose-response meta-analysis. BMJ open. 2019; 9(12): e030513.

McCullough ML, Zoltick ES, Weinstein SJ, Fedirko V, Wang M, Cook NR, et al. Circulating vitamin D and colorectal cancer risk: an international pooling project of 17 cohorts. J Natl Cancer Inst. 2019; 111(2): 158-69.

Fu J, Wu Z, Liu J, Wu T. Vitamin C: A stem cell promoter in cancer metastasis and immunotherapy. Biomed Pharmacother. 2020; 131: 110588.

Fu Y, Xu F, Jiang L, Miao Z, Liang X, Yang J, et al. Circulating vitamin C concentration and risk of cancers: a Mendelian randomization study. BMC Med. 2021; 19(1): 1-14.

Dachs GU, Gandhi J, Wohlrab C, Carr AC, Morrin HR, Pullar JM, et al. Vitamin C administration by intravenous infusion increases tumor ascorbate content in patients with colon cancer: A clinical intervention study. Front Oncol. 2021; 10: 600715.

Chang D, Wang F, Zhao Y-S, Pan H-Z. Evaluation of oxidative stress in colorectal cancer patients. Biomed Environ Sci. 2008; 21(4): 286-89.

Mahdavi R, Faramarzi E, Seyedrezazadeh E, Mohammad-Zadeh M, Pourmoghaddam M. Evaluation of oxidative stress, antioxidant status and serum vitamin C levels in cancer patients. Biol Trace Elem Res. 2009;130(1):1-6.

Saygili E, Konukoglu D, Papila C, Akcay T. Levels of plasma vitamin E, vitamin C, TBARS, and cholesterol in male patients with colorectal tumors. Biochem (Mosc). 2003; 68(3): 325-28.

Yun J, Mullarky E, Lu C, Bosch KN, Kavalier A, Rivera K, et al. Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science. 2015; 350(6266): 1391-96.

Kondo K, Sano R, Goto K, Hiramoto K, Ooi K. Administration of high-dose vitamin C and irinotecan ameliorates colorectal cancer induced by azoxymethane and dextran sodium sulfate in mice. Biol Pharm Bull. 2018; 41(12): 1797-803.

Dachs GU, Gandhi J, Wohlrab C, Carr AC, Morrin HR, Pullar JM, et al. Vitamin C administration by intravenous infusion increases tumor ascorbate content in patients with colon cancer: A clinical intervention study. Front Oncol. 2021; 10: 2984.

Downloads

Published

2023-06-01

Issue

Section

article

How to Cite

1.
The role of Adipocytokines, Vitamin D, and C in Colorectal Cancer. Baghdad Sci.J [Internet]. 2023 Jun. 1 [cited 2024 Apr. 27];20(3):0690. Available from: https://bsj.uobaghdad.edu.iq/index.php/BSJ/article/view/7245

Similar Articles

You may also start an advanced similarity search for this article.