Revealing the Potency of Cinnamon as an Anti-cancer and Chemopreventive Agent

Yonika Arum Larasati, Edy Meiyanto

Abstract


Cinnamon (Cinnamomum spp.), an ancient spice, has been explored as a potential for medicinal purposes. Despite numerous studies about its potency in overcoming of numerous diseases, the potency as anti-cancer would be a challenge. This current article provides a review of the anti-cancer and chemoprevention potency of cinnamon and its major constituents: cinnamaldehyde, cinnamic acid, 2-hydroxycinnamaldehyde, 2-methoxycinnamaldehyde, and eugenol. Comprehensively, cinnamon and its constituents exhibit the anti-cancer and cancer prevention activities through various mechanisms: (1) anti-proliferation, (2) induction of cell death, (3) anti-angiogenesis, (4) anti-metastasis, (5) suppression of tumor-promoted inflammation, (6) immunomodulation, and (7) modulation of redox homeostasis; both in vitro and in vivo. Moreover, cinnamon also shows the synergistic anti-cancer effect with well-known anti-cancer drugs, such as doxorubicin, which support its potency to be used as a combination chemotherapeutic (co-chemotherapeutic) agent. However, further study should be established to determine the exact target molecule(s) of cinnamon in the cancer cells.

Keywords: cinnamon, spice, cancer, anti-cancer, chemopreventive


Full Text:

PDF

References


Alqasoumi, S., 2012, Anti-Secretagogue and Antiulcer Effects of Cinnamon Cinnamomum Zeylanicum in Rats, J. Pharmacognosy Phytother., 4(4), 53-61. CrossRef

Al-Sharif, I., Remmal, A. and Aboussekhra, A., 2013, Eugenol Triggers Apoptosis in Breast Cancer Cells through E2F1/Survivin Down-Regulation, BMC cancer, 13(1), 600. CrossRef

Anjarsari, E.Y., Kristina, N., Larasati, Y.A., Putri, D.D.P. and Meiyanto, E., 2013, Synergistic Effect of Cinnamon Essential Oil (Cinnamomum burmannii) and Doxorubicin on T47D Cells Correlated with Apoptosis Induction, Indones. J. Cancer Chemoprevent., 4(1), 450-456. CrossRef

Bansode, R.R., Leung, T., Randolph, P., Williams, L.L. and Ahmedna, M., 2013, Cinnamon Extract Inhibits Angiogenesis in Zebrafish and Human Endothelial Cells by Suppressing VEGFR1, VEGFR2, and PKC‐mediated MAP Kinase, Food Sci. Nutr., 1(1), 74-82. CrossRef

Barceloux, D.G., 2009, Cinnamon (cinnamomum species), Dis. Mon., 55(6), 327-335. CrossRef

Cabello, C.M., Bair, W.B., Lamore, S.D., Ley, S., Bause, A.S., Azimian, S., et al., 2009, The Cinnamon-Derived Michael Acceptor Cinnamic Aldehyde Impairs Melanoma Cell Proliferation, Invasiveness, and Tumor Growth, Free Radic. Biol. Med., 46(2), 220-231. CrossRef

Chew, E.H., Nagle, A.A., Zhang, Y., Scarmagnani, S., Palaniappan, P., Bradshaw, T.D., et al., 2010, Cinnamaldehydes Inhibit Thioredoxin Reductase and Induce Nrf2: Potential Candidates for Cancer Therapy and Chemoprevention, Free Radic. Biol. Med., 48(1), 98-111. CrossRef

Chuang, L.Y., Guh, J.Y., Chao, L.K., Lu, Y.C., Hwang, J.Y., Yang, Y.L., et al., 2012, Anti-proliferative Effects of Cinnamaldehyde on Human Hepatoma Cell Lines, Food Chem., 133(4), 1603-1610. CrossRef

Daker, M., Lin, V.Y., Akowuah, G.A., Yam, M.F. and Ahmad, M., 2013, Inhibitory Effects of Cinnamomum Burmannii Blume Stem Bark Extract and Trans-Cinnamaldehyde on Nasopharyngeal Carcinoma Cells; Synergism With Cisplatin. Exp. Ther. Med., 5(6), 1701-1709. CrossRef

de Oliveira Niero, E.L. and Machado-Santelli, G.M., 2013, Cinnamic Acid Induces Apoptotic Cell Death and Cytoskeleton Disruption in Human Melanoma Cells, J. Exp. Clin. Cancer Res., 32(1), 31. CrossRef

Deryugina, E.I. and Quigley, J.P., 2006, Matrix Metalloproteinases and Tumor Metastasis, Cancer Metastasis Rev., 25(1), 9-34. CrossRef

Ding, Y., Wu, E.Q., Liang, C., Chen, J., Tran, M.N., Hong, C.H., et al., 2011, Discrimination of Cinnamon Bark and Cinnamon Twig Samples Sourced from Various Countries Using HPLC-based Fingerprint Analysis, Food Chem., 127(2), 755-760. CrossRef

Duke, J.A., 1992, Handbook of Phytochemical Constituents of GRAS Herbs and Other Economic Plants, Boca Raton: CRC Press.

Fang, S.H., Rao, Y.K. and Tzeng, Y.M., 2004, Cytotoxic Effect of Trans-Cinnamaldehyde from Cinnamomum Osmophloeum Leaves on Human Cancer Cell Lines, Int. J. Appl. Sci. Eng., 2(2), 136-147. Link

Finn, O.J., 2012, Immuno-oncology: Understanding the Function and Dysfunction of the Immune System in Cancer, Ann. Oncol., 23(Suppl 8), viii6-9. CrossRef

Hanahan, D. and Weinberg, R.A., 2011, Hallmarks of Cancer: the Next Generation, Cell, 144(5), 646-674. CrossRef

Homma, S., Ishii, Y., Morishima, Y., Yamadori, T., Matsuno, Y., Haraguchi, N., et al., 2009, Nrf2 Enhances Cell Proliferation and Resistance to Anti-Cancer Drugs in Human Lung Cancer, Clin. Cancer Res., 15(10), 3423-3432. CrossRef

Hong, S.H., Kim, J., Kim, J.M., Lee, S.Y., Shin, D.S., Son, K.H., et al., 2007, Apoptosis Induction of 2′-Hydroxycinnamaldehyde as A Proteasome Inhibitor is Associated with ER Stress and Mitochondrial Perturbation in Cancer Cells, Biochem. Pharmacol., 74(4), 557-565. CrossRef

Huang, Y., Zeng, F., Xu, L., Zhou, J., Liu, X. and Le, H., 2012, Anti-Cancer Effects of Cinnamic Acid in Lung Adenocarcinoma Cell Line H1299-Derived Stem-Like Cells, Oncol. Res., 20(11), 499-507. CrossRef

Hussain, A., Brahmbhatt, K., Priyani, A., Ahmed, M., Rizvi, T.A. and Sharma, C., 2011, Eugenol Enhances the Chemotherapeutic Potential of Gemcitabine and Induces Anticarcinogenic and Anti-Inflammatory Activity in Human Cervical Cancer Cells, Cancer Biother. Radiopharm., 26(5), 519-527. CrossRef

Ismail, I.A., Kang, H.S., Lee, H.J., Chang, H., Yun, J., Lee, C.W., et al., 2013, 2-Hydroxycinnamaldehyde Inhibits the Epithelial-Mesenchymal Transition in Breast Cancer Cells, Breast Cancer Res. Treat., 137(3), 697-708. CrossRef

Jaganathan, S.K., Mazumdar, A., Mondhe, D. and Mandal, M., 2011, Apoptotic Effect of Eugenol in Human Colon Cancer Cell Lines, Cell Biol. Int., 35(6), 607-615. CrossRef

Ka, H., Park, H.J., Jung, H.J., Choi, J.W., Cho, K.S., Ha, J., et al., 2003, Cinnamaldehyde Induces Apoptosis by ROS-Mediated Mitochondrial Permeability Transition in Human Promyelocytic Leukemia HL-60 Cells, Cancer Lett., 196(2), 143-152. Link

Kamaliroosta, L., Gharachorloo, M., Kamaliroosta, Z. and KH, A.Z., 2012, Extraction of Cinnamon Essential Oil and Identification of Its Chemical Compounds, J. Med. Plants Res., 6(4), 609-614. CrossRef

Kansanen, E., Kuosmanen, S.M., Leinonen, H. and Levonen, A.L., 2013, The Keap1-Nrf2 Pathway: Mechanisms of Activation and Dysregulation in Cancer, Redox Biol., 1(1), 45-49. CrossRef

Kim, D.H., Kim, C.H., Kim, M.S., Kim, J.Y., Jung, K.J., Chung, J.H., et al., 2007, Suppression of Age-related Inflammatory NF-κB Activation by Cinnamaldehyde, Biogerontology, 8(5),545-554. CrossRef

Kim, S.A., Sung, Y.K., Kwon, B.M., Yoon, J.H., Lee, H., Ahn, S.G., et al., 2010, 2′-Hydroxycinnamaldehyde Shows Antitumor Activity Against Oral Cancer in Vitro and in Vivo in A Rat Tumor Model, Anticancer Res., 30(2), 489-494. Link

Koppikar, S.J., Choudhari, A.S., Suryavanshi, S.A., Kumari, S., Chattopadhyay, S. and Kaul-Ghanekar, R., 2010, Aqueous Cinnamon Extract (ACE-c) from the Bark of Cinnamomum Cassia Causes Apoptosis in Human Cervical Cancer Cell Line (SiHa) through Loss of Mitochondrial Membrane Potential, BMC cancer, 10(1), 210. CrossRef

Kwon, H.K., Jeon, W.K., Hwang, J.S., Lee, C.G., So, J.S., Park, J.A., et al., 2009, Cinnamon Extract Suppresses Tumor Progression by Modulating Angiogenesis and the Effector Function of CD8+ T cells, Cancer Lett., 278(2), 174-182. CrossRef

Kwon, H.K., Hwang, J.S., So, J.S., Lee, C.G., Sahoo, A., Ryu, J.H., et al., 2010, Cinnamon Extract Induces Tumor Cell Death through Inhibition of NFκB and AP1, BMC cancer, 10(1), 392. CrossRef

Larasati, Y.A., Putri, D.D.P., Utomo, R.Y., Hermawan, A. and Meiyanto, E., 2014, Combination of Cisplatin and Cinnamon Essential Oil Inhibits HeLa Cells Proliferation through Cell Cycle Arrest, J. Appl. Pharm. Sci., 4(12), 14-19. CrossRef

Lee, S.Y., Kim, H.S., Kim, J.O., Hwang, S.W. and Hwang, S.Y., 2006, Effect of Ethanol Extracts of Cinnamon on The Proliferation and COX-2 Pathway in HT-29 Human Colon Cancer Cell Line, J. Korean Soc. Food. Sci. Nutr., 35(9), 1115-1120. Link

Lee, C.W., Lee, S.H., Lee, J.W., Ban, J.O., Lee, S.Y., Yoo, H.S., et al., 2007, 2-Hydroxycinnamaldehyde Inhibits SW620 Colon Cancer Cell Growth through AP-1 Inactivation, J. Pharmacol. Sci., 104(1), 19-28. Link

Lee, M.A., Park, H.J., Chung, H.J., Kim, W.K. and Lee, S.K., 2013, Antitumor Activity of 2-Hydroxycinnamaldehyde for Human Colon Cancer Cells Through Suppression of Β-Catenin Signalling, J. Nat. Prod., 76(7), 1278-1284. CrossRef

Ma, Y.Y., Huo, H.R., Li, C.H., Zhao, B.S., Li, L.F., Sui, F., et al., 2008, Effects of Cinnamaldehyde on PGE2 Release and TRPV4 Expression in Mouse Cerebral Microvascular Endothelial Cells Induced by Interleukin-1β, Biol. Pharm. Bull., 31(3), 426-430. Link

Manikandan, P., Vinothini, G., Priyadarsini, R.V., Prathiba, D. and Nagini, S., 2011, Eugenol Inhibits Cell Proliferation via NF-κB Suppression in a Rat Model of Gastric Carcinogenesis Induced by MNNG, Invest. New Drugs., 29(1), 110-117. CrossRef

Mao, J.T., Roth, M.D., Fishbein, M.C., Aberle, D.R., Zhang, Z.F., Rao, J.Y., et al., 2011, Lung Cancer Chemoprevention with Celecoxib in Former Smokers, Cancer Prev. Res., 4(7), 984-993. CrossRef

Nagle, A.A., Gan, F.F., Jones, G., So, C.L., Wells, G. and Chew, E.H., 2012, Induction of Tumor Cell Death through Targeting Tubulin and Evoking Dysregulation of Cell Cycle Regulatory Proteins by Multifunctional Cinnamaldehydes, PloS One, 7(11), e50125. CrossRef

Patra, K., Bose, S., Sarkar, S., Rakshit, J., Jana, S., Mukherjee, A., et al., 2012, Amelioration of Cyclophosphamide Induced Myelosuppression and Oxidative Stress by Cinnamic Acid, Chem.-Biol. Interact., 195(3), 231-239. CrossRef

Ranasinghe, P., Jayawardana, R., Galappaththy, P., Constantine, G.R., de Vas Gunawardana, N. and Katulanda, P., 2012, Efficacy and Safety of ‘True’cinnamon (Cinnamomum zeylanicum) as a Pharmaceutical Agent in Diabetes: a Systematic Review and Meta‐analysis, Diabet. Med., 29(12), 1480-1492. CrossRef

Ranasinghe, P., Pigera, S., Premakumara, G.S., Galappaththy, P., Constantine, G.R. and Katulanda, P., 2013, Medicinal Properties of ‘True’cinnamon (Cinnamomum zeylanicum): A Systematic Review, BMC Complement. Altern. Med., 13(1), 275. CrossRef

Schoene, N.W., Kelly, M.A., Polansky, M.M. and Anderson, R.A., 2005, Water-soluble Polymeric Polyphenols from Cinnamon Inhibit Proliferation and Alter Cell Cycle Distribution Patterns of Hematologic Tumor Cell Lines, Cancer Lett., 230(1), 134-140. CrossRef

Shibata, T., Kokubu, A., Gotoh, M., Ojima, H., Ohta, T., Yamamoto, M., et al., 2008, Genetic Alteration of Keap1 Confers Constitutive Nrf2 Activation and Resistance to Chemotherapy in Gallbladder Cancer, Gastroenterology, 135(4), 1358-1368. CrossRef

Singh, R., Koppikar, S.J., Paul, P., Gilda, S., Paradkar, A.R. and Kaul-Ghanekar, R., 2009, Comparative Analysis of Cytotoxic Effect of Aqueous Cinnamon Extract from Cinnamomum zeylanicum Bark With Commercial Cinnamaldehyde on Various Cell Lines, Pharm. Biol., 47(12), 1174-1179. CrossRef

Sosa, V., Moliné, T., Somoza, R., Paciucci, R., Kondoh, H. and LLeonart, M.E., 2013, Oxidative Stress and Cancer: An Overview, Ageing Res. Rev,. 12(1), 376-390. CrossRef

Tsai, C.M., Sun, F.M., Chen, Y.L., Hsu, C.L., Yen, G.C. and Weng, C.J., 2013, Molecular Mechanism Depressing PMA-induced Invasive Behaviors in Human Lung Adenocarcinoma Cells by Cis-And Trans-Cinnamic Acid, Eur. J. Pharm. Sci., 48(3), 494-501. CrossRef

Wondrak, G.T., 2009, Redox-directed Cancer Therapeutics: Molecular Mechanisms and Opportunities, Antioxid. Redox Signal., 11(12), 3013-3069. CrossRef

Wondrak, G.T., Villeneuve, N.F., Lamore, S.D., Bause, A.S., Jiang, T. and Zhang, D.D., 2010, The Cinnamon-Derived Dietary Factor Cinnamic Aldehyde Activates the Nrf2-Dependent Antioxidant Response in Human Epithelial Colon Cells, Molecules, 15(5), 3338-3355. CrossRef

Yamakawa, D., Kidoya, H., Sakimoto, S., Jia, W. and Takakura, N., 2011, 2-Methoxycinnamaldehyde Inhibits Tumor Angiogenesis by Suppressing Tie2 Activation, Biochem. Biophys. Res. Commun., 415(1), 174-180. CrossRef

Yen, G.C., Chen, Y.L., Sun, F.M., Chiang, Y.L., Lu, S.H. and Weng, C.J., 2011, A Comparative Study on The Effectiveness of Cis-and Trans-form of Cinnamic Acid Treatments for Inhibiting Invasive Activity of Human Lung Adenocarcinoma Cells, Eur. J. Pharm. Sci., 44(3), 281-287. CrossRef

Yu, T., Lee, S., Yang, W.S., Jang, H.J., Lee, Y.J., Kim, T.W., et al., 2012, The Ability of an Ethanol Extract of Cinnamomum cassia to Inhibit Src and Spleen Tyrosine Kinase Activity Contributes to Its Anti-inflammatory Action, J. Ethnopharmacol., 139(2), 566-573. CrossRef

Zhang, J.H., Liu, L.Q., He, Y.L., Kong, W.J. and Huang, S.A., 2010, Cytotoxic Effect of Trans-Cinnamaldehyde on Human Leukemia K562 Cells, Acta Pharmacol. Sin., 31(7), 861-866. CrossRef

Zhang, C., Li, C., Sui, F., Lu, Y., Li, L., Guo, S., et al., 2012, Cinnamaldehyde Decreases Interleukin-1beta Induced PGE2 Production by Down-regulation of mPGES-1 and COX-2 Expression in Mouse Macrophage RAW264. 7 cells, Zhongguo Zhong Yao Za Zhi., 37(9), 1274-1278. Link




DOI: http://dx.doi.org/10.14499/indonesianjcanchemoprev9iss1pp47-62

Copyright (c) 2018 Yonika Arum Larasati, Edy Meiyanto

Indexed by:

                  

               

 

Indonesian Society for Cancer Chemoprevention