Anticancer, C. verum J. Presl, Cinnamaldehyde, Cinnamic acid, Eugenol, Oral squamous cell carcinoma
Citation Information :
Varadarajan S, Narasimhan M, Balaji TM, Chamundeeswari DP, Sakthisekaran D. In Vitro Anticancer Effects of Cinnamomum verum J. Presl, Cinnamaldehyde, 4 Hydroxycinnamic Acid and Eugenol on an Oral Squamous Cell Carcinoma Cell Line. J Contemp Dent Pract 2020; 21 (9):1027-1033.
Aim and objective: The present study was conducted to assess the in vitro anticancer effects of Cinnamomum verum J. Presl extract and its active constituents, such as cinnamaldehyde, 4 hydroxycinnamic acid, and eugenol on oral squamous cell carcinoma cell line. Materials and methods: Aqueous, ethanolic, and hydroalcoholic extracts of C. verum J. Presl (bark) were prepared using standardized protocols. Cinnamaldehyde, 4 hydroxycinnamic acid, and eugenol were quantified in the extracts. Total saponins, tannins, and polyphenols were quantified in the selected extracts. A commercially available SCC25 cell line was cultured according to standard protocol. The anticancer effects of the extract, active compounds, and standard cisplatin were assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cytotoxicity, acridine orange/ethidium bromide staining, DNA, fragmentation assay, cell cycle analysis by flow cytometry, and JC-1 staining (5,5′,6,6′-tetrachloro1,1′,3,3′tetraethylbenzimidazolylcarbocyanine iodide). Results: The hydroalcoholic extracts demonstrated a higher quantity of the active ingredients cinnamaldehyde, 4 hydroxycinnamic acid, and eugenol. The selected extract and active compounds demonstrated anticancer effects via apoptosis induction and S-phase arrest. Apoptosis induction was exerted by the extract via alteration in mitochondrial membrane potential. Conclusion:Cinnamomum verum J. Presl and its active compounds exhibited in vitro anticancer effects on oral squamous cell carcinoma. Further studies in animal models have to be carried out to assess toxicity and in vivo effects. Clinical significance: The anticancer properties of Cinnamomum verum J. Presl could be explored further for prevention and management of oral squamous cell carcinoma.
Prasad LK. Burden of oral cancer: an Indian scenario. J Orofac Sci 2014;6(2):77. DOI: 10.4103/0975-8844.143043.
Shukla S, Shukla S. Oral cancer-curse, cure and challenge. Indian J Surg 2012;74(6):437–439. DOI: 10.1007/s12262-012-0769-0.
Mohd Bakri M, Mohd Hussaini H, Rachel Holmes A, et al. Revisiting the association between candidal infection and carcinoma, particularly oral squamous cell carcinoma. J Oral Microbiol 2010;2(1). DOI: 10.3402/jom.v2i0.5780.
Valko M, Rhodes CJ, Moncol J, et al. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 2006;160(1):1–40. DOI: 10.1016/j.cbi.2005.12.009.
Schwartz J, Pavlova S, Kolokythas A, et al. Streptococci-human papilloma virus interaction with ethanol exposure leads to keratinocyte damage. J Oral Maxillofac Surg 2012;70(8):1867–1879. DOI: 10.1016/j.joms.2011.08.005.
Chulasiri M, Picha P, Rienkijkan M, et al. The cytotoxic effect of petroleum ether and chloroform extracts from Ceylon cinnamon (Cinnamomum zeylanicum Nees) barks on tumor cells in vitro. Int J Crude Drug Res 1984;22(4):177–180. DOI: 10.3109/13880208409070672.
Varalakshmi B, Vijaya Anand A, Karpagam T, et al. In-vitro antimicrobial and anticancer activity of Cinnamomum zeylanicum Linn bark extracts. Int J Pharm Pharmaceut Sci 2014;6(1):12–18.
Manal A, Hanan F, Sanaa A, et al. In vitro and in vivo assessment of some functional foods against initiation of hepatocellular carcinoma. J Basic Appl Sci Res 2012;2(1):471–483.
Scott T, Bladt S, Zgainski E. Plant drug analysis: A thin layer chromatography Atlas. Berlin Heidelberg: Springer; 2013.
Charde M, Chakolkar M, Welankiwar A, et al. Development of validated HPTLC method for the estimation of eugenol in marketed herbal formulation of muscle and joint HRX pain relieving oil. Int J Phytopharm 2014;4(1):28–32.
Gopu C, Aher S, Mehta H, et al. Simultaneous determination of cinnamaldehyde, eugenol and piperine by HPTLC densitometric method. Phytochem Anal 2008;19(2):116–121. DOI: 10.1002/pca.1022.
Ainsworth E, Gillespie K. Estimation of total phenolic content and other oxidation substrates in plant tissues using Folin–Ciocalteu reagent. Nat Protoc 2007;2(4):875–877. DOI: 10.1038/nprot.2007.102.
Ceyhun Sezgin A, Art PkN. Determination of saponin content in turkish tahini Halvah by using HPLC. Adv J Food Sci Technol 2010;2(2):109–115.
Carmichael J, Mitchell J, DeGraff W, et al. Chemosensitivity testing of human lung cancer cell lines using the MTT assay. Br J Cancer 1988;57(6):540–547. DOI: 10.1038/bjc.1988.125.
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. DOI: 10.1016/0022-1759(83)90303-4.
Kotamraju S, Konorev E, Joseph J, et al. Doxorubicin-induced apoptosis in endothelial cells and cardiomyocytes is ameliorated by nitrone spin traps and ebselen: Role of reactive oxygen and nitrogen species. J Biolog Chemis 2006;275(43):33585–33592. DOI: 10.1074/jbc.M003890200.
Axel HS. Checkpoint controls and cancer. Totowa, NJ: Humana Press Inc.; 2004. 301–311p.
Salido M, Gonzalez J, Vilches J. Loss of mitochondrial membrane potential is inhibited by bombesin in etoposide-induced apoptosis in PC-3 prostate carcinoma cells. Mol Cancer Ther 2007;6(4):1292–1299. DOI: 10.1158/1535-7163.MCT-06-0681.
WHO monographs on selected medicinal plants, vol. 1, Geneva: World Health Organization; 1999. pp. 95–105.
Shih-Hua F, Yerra K, Yew-Min T. Cytotoxic effect of trans-cinnamaldehyde from Cinnamomum osmophloeum leaves on human cancer cell lines. Int J Appl Sci Engineer 2004;2(2):36–147.
Kim SA, Sung YK, Kwon BM, et al. 2’-Hydroxycinnamaldehyde shows antitumor activity against oral cancer in vitro and in vivo in a rat tumor model. Anticancer Res 2010;30(2):489–494.
Niero E, Machado-Santelli G. Cinnamic acid induces apoptotic cell death and cytoskeleton disruption in human melanoma cells. J Exp Clin Cancer Res 2013;32(1):31. DOI: 10.1186/1756-9966-32-31.
Jian Z, Aiju X, Tuanjie W, et al. Effect and mechanism of action of cinnamic acid on the proliferation and apoptosis of leukaemia cells. Biomed Res 2014;25(3):405–408.
Kim DJ, Koh JM, Lee O, et al. Caspases-dependent apoptosis in human melanoma cell by eugenol. Korean J Anat 2006;39(3):245–253. DOI: 10.1016/j.bone.2006.03.004.
Ghosh R, Nadiminty N, Fitzpatrick J, et al. Eugenol causes melanoma growth suppression through inhibition of E2F1 transcriptional activity. J Biolog Chem 2005;280(7):5812–5819. DOI: 10.1074/jbc.M411429200.
Rothschild A. Mechanisms of histamine release by compound 48/80. Br J Pharmacol 1970;38(1):253–262. DOI: 10.1111/j.1476-5381.1970.tb10354.x.
Shin S, Park J, Kim G. The mechanism of apoptosis induced by eugenol in human osteosarcoma cells. J Korean Oral Maxillofac Surg 2007;3:20–27.
Man S, Gao W, Zhang Y, et al. Chemical study and medical application of saponins as anti-cancer agents. Fitoterapia 2010;81(7):703–714. DOI: 10.1016/j.fitote.2010.06.004.
Huang W, Cai Y, Zhang Y. Natural phenolic compounds from medicinal herbs and dietary plants: potential use for cancer prevention. Nutr Cancer 2009;62(1):1–20. DOI: 10.1080/01635580903191585.