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Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Lauric Acid Modulates Cancer-Associated microRNA Expression and Inhibits the Growth of the Cancer Cell

Author(s): Poonam Verma, Amit Ghosh*, Manisha Ray and Saurav Sarkar

Volume 20, Issue 7, 2020

Page: [834 - 844] Pages: 11

DOI: 10.2174/1871520620666200310091719

Price: $65


Background: microRNAs are known to regulate various protein-coding gene expression posttranscriptionally. Fatty acids are cell membrane constituents and are also known to influence the biological activities of the cells like signal transduction, growth and differentiation of the cells, apoptosis induction, and other physiological functions. In our experiments, we used lauric acid to analyse its effects on human cancerous cell lines.

Objective: Our objective was to speculate the miRNA expression profile in lauric acid treated and untreated cancerous cell lines and further study the metabolic pathways of the targeted tumour suppressor and oncogenes.

Methods: The KB cells and HepG2 cells were treated with lauric acid and miRNA was isolated and the expression of tumour suppressor and oncogenic miRNA was measured by quantitative PCR. The untreated cells were used as control. The metabolic pathways of the target tumour suppressor and oncogenes were examined by GeneMANIA software.

Results: Interestingly, the lauric acid treatment suppresses the expression of oncogenic miRNA and significantly upregulated the expression of some tumour suppressor miRNAs. GeneMANIA metabolic pathway revealed that the upregulated tumour suppressor miRNAs regulate several cancer-associated pathways such as DNA damage, signal transduction p53 class mediator, stem cell differentiation, cell growth, cell cycle phase transition, apoptotic signalling pathway, cellular response to stress and radiation, etc. whereas oncogenic miRNAs regulate the cancer-associated pathway like cell cycle phase transition, apoptotic signalling pathway, cell growth, response to oxidative stress, immune response activating cell surface protein signalling pathway, cyclin-dependent protein kinase activity, epidermal growth factor receptor signalling pathways, etc.

Conclusion: In our study, we found that lauric acid works as an anticancer agent by altering the expression of miRNAs.

Keywords: miRNA, lauric acid, anticancer activity, metabolic pathways, tumour suppressor, oncogenes.

Graphical Abstract
Engelbrecht, A.M.; Toit-Kohn, J.L.; Ellis, B.; Thomas, M.; Nell, T.; Smith, R. Differential induction of apoptosis and inhibition of the PI3-kinase pathway by saturated, monounsaturated and polyunsaturated fatty acids in a colon cancer cell model. Apoptosis, 2008, 13(11), 1368-1377.
[] [PMID: 18785011]
Bocca, C.; Bozzo, F.; Gabriel, L.; Miglietta, A. Conjugated linoleic acid inhibits Caco-2 cell growth via ERK-MAPK signaling pathway. J. Nutr. Biochem., 2007, 18(5), 332-340.
[] [PMID: 16963252]
Jump, D.B.; Clarke, S.D. Regulation of gene expression by dietary fat. Annu. Rev. Nutr., 1999, 19, 63-90.
[] [PMID: 10448517]
Risérus, U. Fatty acids and insulin sensitivity. Curr. Opin. Clin. Nutr. Metab. Care, 2008, 11(2), 100-105.
[] [PMID: 18301083]
Calder, P.C. Functional roles of fatty acids and their effects on human health. JPEN J. Parenter. Enteral Nutr., 2015, 39(1)(Suppl.), 18S-32S.
[] [PMID: 26177664]
Dayrit, F.M. The properties of lauric acid and their significance in coconut oil. J. Am. Oil Chem. Soc., 2015, 92, 1-15.
Kappally, S.; Shirwaikar, A.; Shirwaikar, A. Coconut oil – a review of potential applications. Hygeia J. D. Med., 2015, 7, 34-41.
Eyres, L.; Eyres, M.F.; Chisholm, A.; Brown, R.C. Coconut oil consumption and cardiovascular risk factors in humans. Nutr. Rev., 2016, 74(4), 267-280.
[] [PMID: 26946252]
Kadochi, Y.; Mori, S.; Fujiwara-Tani, R.; Luo, Y.; Nishiguchi, Y.; Kishi, S.; Fujii, K.; Ohmori, H.; Kuniyasu, H. Remodeling of energy metabolism by a ketone body and medium-chain fatty acid suppressed the proliferation of CT26 mouse colon cancer cells. Oncol. Lett., 2017, 14(1), 673-680.
[] [PMID: 28693220]
Fauser, J.K.; Matthews, G.M.; Cummins, A.G.; Howarth, G.S. Induction of apoptosis by the medium-chain length fatty acid lauric acid in colon cancer cells due to induction of oxidative stress. Chemotherapy, 2013, 59(3), 214-224.
[] [PMID: 24356281]
Pritchard, C.C.; Cheng, H.H.; Tewari, M. MicroRNA profiling: approaches and considerations. Nat. Rev. Genet., 2012, 13(5), 358-369.
[] [PMID: 22510765]
Ameres, S.L.; Zamore, P.D. Diversifying microRNA sequence and function. Nat. Rev. Mol. Cell Biol., 2013, 14(8), 475-488.
[] [PMID: 23800994]
Ramachandran, R.; Fausett, B.V.; Goldman, D. Ascl1a regulates Müller glia dedifferentiation and retinal regeneration through a Lin-28-dependent, let-7 microRNA signalling pathway. Nat. Cell Biol., 2010, 12(11), 1101-1107.
[] [PMID: 20935637]
Esquela-Kerscher, A.; Slack, F.J. Oncomirs - microRNAs with a role in cancer. Nat. Rev. Cancer, 2006, 6(4), 259-269.
[] [PMID: 16557279]
Weng, W.H.; Leung, W.H.; Pang, Y.J.; Hsu, H.H. Lauric acid can improve the sensitization of Cetuximab in KRAS/BRAF mutated colorectal cancer cells by retrievable microRNA-378 expression. Oncol. Rep., 2016, 35(1), 107-116.
[] [PMID: 26496897]
Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods, 1983, 65(1-2), 55-63.
[] [PMID: 6606682]
Livak, K.J.; Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 2001, 25(4), 402-408.
[] [PMID: 11846609]
Ibarguren, M.; López, D.J.; Escribá, P.V. The effect of natural and synthetic fatty acids on membrane structure, microdomain organization, cellular functions and human health. Biochim. Biophys. Acta, 2014, 1838(6), 1518-1528.
[] [PMID: 24388951]
Li, G.; Wang, K.; Wang, J.; Qin, S.; Sun, X.; Ren, H. miR-497-5p inhibits tumor cell growth and invasion by targeting SOX5 in non-small-cell lung cancer. J. Cell. Biochem., 2019, 120(6), 10587-10595.
[] [PMID: 30816573]
Yang, Q.; Yu, W.; Han, X. Overexpression of microRNA‑101 causes anti‑tumor effects by targeting CREB1 in colon cancer. Mol. Med. Rep., 2019, 19(4), 3159-3167.
[] [PMID: 30816471]
Lappano, R.; Sebastiani, A.; Cirillo, F.; Rigiracciolo, D.C.; Galli, G.R.; Curcio, R.; Malaguarnera, R.; Belfiore, A.; Cappello, A.R.; Maggiolini, M. The lauric acid-activated signaling prompts apoptosis in cancer cells. Cell Death Discov., 2017, 3, 17063.
[] [PMID: 28924490]
De Matteis, V.; Cascione, M.; De Giorgi, M.L.; Leporatti, S.; Rinaldi, R. Encapsulation of thermo-sensitive lauric acid in silica shell: A green derivate for chemo-thermal therapy in breast cancer cell. Molecules, 2019, 24(11)E2034
[] [PMID: 31141939]
Famurewa, A.C.; Ufebe, O.G.; Egedigwe, C.A.; Nwankwo, O.E.; Obaje, G.S. Virgin coconut oil supplementation attenuates acute chemotherapy hepatotoxicity induced by anticancer drug methotrexate via inhibition of oxidative stress in rats. Biomed. Pharmacother., 2017, 87, 437-442.
[] [PMID: 28068634]
Famurewa, A.C.; Folawiyo, A.M.; Enohnyaket, E.B.; Azubuike-Osu, S.O.; Abi, I.; Obaje, S.G.; Famurewa, O.A. Beneficial role of virgin coconut oil supplementation against acute methotrexate chemotherapy-induced oxidative toxicity and inflammation in rats. Integr. Med. Res., 2018, 7(3), 257-263.
[] [PMID: 30271714]
Alex, A.; Nair, N.K.; Tomy, S.; Elango, K.; Achuthan, C.R. A study on the effect of virgin coconut oil on benzo(A) pyrene induced gastric neoplasia in mice. Int. J. Pharm. Sci. Res., 2016, 7(5), 1948-1955.
Farooqi, A.A.; Fuentes-Mattei, E.; Fayyaz, S.; Raj, P.; Goblirsch, M.; Poltronieri, P.; Calin, G.A. Interplay between epigenetic abnormalities and deregulated expression of microRNAs in cancer. Semin. Cancer Biol., 2019, 58, 47-55.
[] [PMID: 30742906]
Verma, P.; Naik, S.; Nanda, P.; Banerjee, S.; Naik, S.; Ghosh, A. In vitro anticancer activity of virgin coconut oil and its fractions in liver and oral cancer cells. Anticancer. Agents Med. Chem., 2019, 19(18), 2223-2230.
[] [PMID: 31736449]
Zhao, J.; Fang, Z.; Zha, Z.; Sun, Q.; Wang, H.; Sun, M.; Qiao, B. Quercetin inhibits cell viability, migration and invasion by regulating miR-16/HOXA10 axis in oral cancer. Eur. J. Pharmacol., 2019, 847, 11-18.
[] [PMID: 30639311]
Kolokythas, A.; Miloro, M.; Zhou, X. Review of MicroRNA deregulation in oral cancer. Part I. J. Oral Maxillofac. Res., 2011, 2(2), e1
[] [PMID: 24421988]
Takeshita, F.; Patrawala, L.; Osaki, M.; Takahashi, R.U.; Yamamoto, Y.; Kosaka, N.; Kawamata, M.; Kelnar, K.; Bader, A.G.; Brown, D.; Ochiya, T. Systemic delivery of synthetic microRNA-16 inhibits the growth of metastatic prostate tumors via downregulation of multiple cell-cycle genes. Mol. Ther., 2010, 18(1), 181-187.
[] [PMID: 19738602]
Calin, G.A.; Cimmino, A.; Fabbri, M.; Ferracin, M.; Wojcik, S.E.; Shimizu, M.; Taccioli, C.; Zanesi, N.; Garzon, R.; Aqeilan, R.I.; Alder, H.; Volinia, S.; Rassenti, L.; Liu, X.; Liu, C.G.; Kipps, T.J.; Negrini, M.; Croce, C.M. MiR-15a and miR-16-1 cluster functions in human leukemia. Proc. Natl. Acad. Sci. USA, 2008, 105(13), 5166-5171.
[] [PMID: 18362358]
Kulkarni, V.; Uttamani, J.R.; Naqvi, A.R.; Nares, S. microRNAs: Emerging players in oral cancers and inflammatory disorders. Tumour Biol., 2017, 39(5), 1010428317698379
[] [PMID: 28459366]
Yang, J.; Cao, Y.; Sun, J.; Zhang, Y. Curcumin reduces the expression of Bcl-2 by upregulating miR-15a and miR-16 in MCF-7 cells. Med. Oncol., 2010, 27(4), 1114-1118.
[] [PMID: 19908170]
Saini, S.; Arora, S.; Majid, S.; Shahryari, V.; Chen, Y.; Deng, G.; Yamamura, S.; Ueno, K.; Dahiya, R. Curcumin modulates microRNA-203-mediated regulation of the Src-Akt axis in bladder cancer. Cancer Prev. Res. (Phila.), 2011, 4(10), 1698-1709.
[] [PMID: 21836020]
Cimmino, A.; Calin, G.A.; Fabbri, M.; Iorio, M.V.; Ferracin, M.; Shimizu, M.; Wojcik, S.E.; Aqeilan, R.I.; Zupo, S.; Dono, M.; Rassenti, L.; Alder, H.; Volinia, S.; Liu, C.G.; Kipps, T.J.; Negrini, M.; Croce, C.M. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc. Natl. Acad. Sci. USA, 2005, 102(39), 13944-13949.
[] [PMID: 16166262]
Cheng, B.; Ding, F.; Huang, C.Y.; Xiao, H.; Fei, F.Y.; Li, J. Role of miR-16-5p in the proliferation and metastasis of hepatocellular carcinoma. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(1), 137-145.
[PMID: 30657555]
Lim, H.S.; Kim, C.S.; Kim, J.S.; Yu, S.K.; Go, D.S.; Lee, S.A.; Moon, S.M.; Chun, H.S.; Kim, S.G.; Kim, D.K. Suppression of oral carcinoma oncogenic activity by microRNA-203 via Down-regulation of SEMA6A. Anticancer Res., 2017, 37(10), 5425-5433.
[PMID: 28982852]
Mahati, S.; Xiao, L.; Yang, Y.; Mao, R.; Bao, Y. miR-29a suppresses growth and migration of hepatocellular carcinoma by regulating CLDN1. Biochem. Biophys. Res. Commun., 2017, 486(3), 732-737.
[] [PMID: 28342862]
Zhou, W.; Zou, B.; Liu, L.; Cui, K.; Gao, J.; Yuan, S.; Cong, N. MicroRNA-98 acts as a tumor suppressor in hepatocellular carcinoma via targeting SALL4. Oncotarget, 2016, 7(45), 74059-74073.
[] [PMID: 27677076]
Ting, H.J.; Messing, J.; Yasmin-Karim, S.; Lee, Y.F. Identification of microRNA-98 as a therapeutic target inhibiting prostate cancer growth and a biomarker induced by vitamin D. J. Biol. Chem., 2013, 288(1), 1-9.
[] [PMID: 23188821]
Koduru, S.V.; Leberfinger, A.N.; Kawasawa, Y.I.; Mahajan, M.; Gusani, N.J.; Sanyal, A.J.; Ravnic, D.J. Non-coding RNAs in Various Stages of Liver Disease Leading to Hepatocellular Carcinoma: Differential Expression of miRNAs, piRNAs, lncRNAs, circRNAs, and sno/mt-RNAs. Sci. Rep., 2018, 8(1), 7967.
[] [PMID: 29789629]
Li, L.M.; Hu, Z.B.; Zhou, Z.X.; Chen, X.; Liu, F.Y.; Zhang, J.F.; Shen, H.B.; Zhang, C.Y.; Zen, K. Serum microRNA profiles serve as novel biomarkers for HBV infection and diagnosis of HBV-positive hepatocarcinoma. Cancer Res., 2010, 70(23), 9798-9807.
[] [PMID: 21098710]
Zhao, X.; Yang, Z.; Li, G.; Li, D.; Zhao, Y.; Wu, Y.; Robson, S.C.; He, L.; Xu, Y.; Miao, R.; Zhao, H. The role and clinical implications of microRNAs in hepatocellular carcinoma. Sci. China Life Sci., 2012, 55(10), 906-919.
[] [PMID: 23108868]
Li, J.; Huang, H.; Sun, L.; Yang, M.; Pan, C.; Chen, W.; Wu, D.; Lin, Z.; Zeng, C.; Yao, Y.; Zhang, P.; Song, E. MiR-21 indicates poor prognosis in tongue squamous cell carcinomas as an apoptosis inhibitor. Clin. Cancer Res., 2009, 15(12), 3998-4008.
[] [PMID: 19509158]
Gombos, K.; Horváth, R.; Szele, E.; Juhász, K.; Gocze, K.; Somlai, K.; Pajkos, G.; Ember, I.; Olasz, L. miRNA expression profiles of oral squamous cell carcinomas. Anticancer Res., 2013, 33(4), 1511-1517.
[PMID: 23564792]
Roy, S.; Khanna, S.; Hussain, S.R.; Biswas, S.; Azad, A.; Rink, C.; Gnyawali, S.; Shilo, S.; Nuovo, G.J.; Sen, C.K. MicroRNA expression in response to murine myocardial infarction: miR-21 regulates fibroblast metalloprotease-2 via phosphatase and tensin homologue. Cardiovasc. Res., 2009, 82(1), 21-29.
[] [PMID: 19147652]
Chang, C.C.; Yang, Y.J.; Li, Y.J.; Chen, S.T.; Lin, B.R.; Wu, T.S.; Lin, S.K.; Kuo, M.Y.; Tan, C.T. MicroRNA-17/20a functions to inhibit cell migration and can be used a prognostic marker in oral squamous cell carcinoma. Oral Oncol., 2013, 49(9), 923-931.
[] [PMID: 23602254]
Wagenaar, T.R.; Zabludoff, S.; Ahn, S.M.; Allerson, C.; Arlt, H.; Baffa, R.; Cao, H.; Davis, S.; Garcia-Echeverria, C.; Gaur, R.; Huang, S.M.; Jiang, L.; Kim, D.; Metz-Weidmann, C.; Pavlicek, A.; Pollard, J.; Reeves, J.; Rocnik, J.L.; Scheidler, S.; Shi, C.; Sun, F.; Tolstykh, T.; Weber, W.; Winter, C.; Yu, E.; Yu, Q.; Zheng, G.; Wiederschain, D. Anti-miR-21 suppresses hepatocellular carcinoma growth via broad transcriptional network deregulation. Mol. Cancer Res., 2015, 13(6), 1009-1021.
[] [PMID: 25758165]
Tao, J.; Jiang, L.; Chen, X. Roles of microRNA in liver cancer. Liver Res., 2018, 2(2), 61-72.
Tomimaru, Y.; Eguchi, H.; Nagano, H.; Wada, H.; Tomokuni, A.; Kobayashi, S.; Marubashi, S.; Takeda, Y.; Tanemura, M.; Umeshita, K.; Doki, Y.; Mori, M. MicroRNA-21 induces resistance to the anti-tumour effect of interferon-α/5-fluorouracil in hepatocellular carcinoma cells. Br. J. Cancer, 2010, 103(10), 1617-1626.
[] [PMID: 20978511]
Pan, X.; Wang, Z.X.; Wang, R. MicroRNA-21: a novel therapeutic target in human cancer. Cancer Biol. Ther., 2010, 10(12), 1224-1232.
[] [PMID: 21139417]
Gong, J.; He, X.X.; Tian, A. Emerging role of microRNA in hepatocellular carcinoma (Review). Oncol. Lett., 2015, 9(3), 1027-1033.
[] [PMID: 25663852]
Su, X.; Wang, H.; Ge, W.; Yang, M.; Hou, J.; Chen, T.; Li, N.; Cao, X. An in vivo method to identify microRNA targets not predicted by computation algorithms: p21 targeting by miR-92a in cancer. Cancer Res., 2015, 75(14), 2875-2885.
[] [PMID: 26062558]
Drury, R.E.; O’Connor, D.; Pollard, A.J. The clinical application of MicroRNAs in infectious disease. Front. Immunol., 2017, 8, 1182.
[] [PMID: 28993774]

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