β-caryophyllene Modulate the Inflammatory and Apoptotic Signally Cascades to Alter the Cellular Response during DMBA Induced Experimental Oral Carcinogenesis; A Histological and In-silico Study
Authors
-
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Chidambaram, Annamalainagar – 608002, Tamil Nadu ,IN
Ramachandhiran Duraisamy -
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Chidambaram, Annamalainagar – 608002, Tamil Nadu ,INBabukumar Sukumar
-
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Chidambaram, Annamalainagar – 608002, Tamil Nadu ,INSankaranarayanan Chandrasekaran
-
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Chidambaram, Annamalainagar – 608002, Tamil Nadu ,INVinothkumar Veerasamy
DOI:
https://doi.org/10.18311/ti/2021/v28i2/27154Keywords:
Antioxidant, Apoptosis, β-caryophyllene, Detoxification Enzymes, DMBA, Oral CancerAbstract
β-caryophyllene (BCP) is a more efficient pro-oxidant and anti-cancer property in our previous in-vitro studies. The motivation behind the present examination was to research the anticancer properties of BCP and its molecular mechanism on 7,12-dimethylbenz(a)anthracene (DMBA) treated hamsters. Hamsters were painted with 0.5% DMBA 3 times a week for 10 weeks to developed oral tumor and showed well progressed hyperplasia, dysplasia and differentiated Oral Squamous Cell Carcinoma (OSCC). DMBA alone treated hamster observed 100% tumor formation, elevated tumor incidence, volume and burden, lipid oxidation by-products, diminish antioxidant levels, body weight and imbalance of detoxification enzymes, along with up-regulation of inflammatory (NFҡB, TNF-α, COX-2, iNOS, IL-6), mutant p53, anti-apoptotic (Bcl2) and down regulation of pro-apoptotic (Bax and caspase-9) markers expressions were observed. Oral pre-administration of BCP at different concentration (100, 200 and 400 mg/kg bw) to DMBA-treated hamsters for 14 weeks, completely prevent the OSCC and restored the above biochemical parameters to near normal level, while histological and western blotting investigation were positive support to the biochemical discoveries. These results indicated that BCP potentially inhibit the inflammatory, anti-apoptotic markers and up-regulate the pro-apoptotic markers. Based on our present finding BCP inhibit cancer cell progression and enhances the apoptosis in DMBA induced oral carcinogenesis. In-silico docking investigation was done to supplement the exploratory outcomes.
Downloads
Published
How to Cite
Issue
Section
Accepted 2021-04-17
Published 2021-05-31
References
World Health Organization. 2020. Oral cancer facts. 2020. www.oralcancerfoundation.org
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries CA Cancer J Clin. 2018; 68(6):394–424. PMid: 30207593. https://doi.org/10.3322/caac.21492 DOI: https://doi.org/10.3322/caac.21492
Speicher DJ, Ramirez-Amador V, Dittmer DP, Webster-Cyriaque J, Goodman MT, Moscicki AB. Viral infections associated with oral cancers and diseases in the context of HIV: A workshop report. Oral Dis. 2016; 22 181–92. PMid: 27109286 PMCid: PMC5590239. https://doi.org/10.1111/odi.12418 DOI: https://doi.org/10.1111/odi.12418
Yusuf N, Nasti TH, Ahmad I, et al. In vivo suppression of Heat Shock Protein (HSP)27 and HSP70 accelerates DMBA-induced skin carcinogenesis by inducing antigenic unresponsiveness to the initiating carcinogenic chemical. J Immunol. 2015; 194(10):4796– 803. PMid: 25840912 PMCid: PMC4648556. https://doi.org/10.4049/jimmunol.1402804 DOI: https://doi.org/10.4049/jimmunol.1402804
Irigaray P, Belpomme D. Basic properties and molecular mechanisms of exogenous chemical carcinogens. Carcinogenesis. 2010; 31(2):135–48. PMid:19858070. https://doi.org/10.1093/carcin/bgp252 DOI: https://doi.org/10.1093/carcin/bgp252
Babukumar S, Vinothkumar V, Velu P, Ramachandhiran D, Ramados Nirmal M. Molecular effects of hesperetin, a citrus flavanone on 7,12-dimethylbenz(a)anthracene induced buccal pouch squamous cell carcinoma in golden Syrian hamsters. Arch Physiol Biochem. 2017; 123(4):265–78. PMid: 28457144. https://doi.org/10.1080/13813455.2017.1317815
Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, Squadrito F, Altavilla D, Bitto A. Oxidative stress: Harms and benefits for human health. Oxid Med Cell Longev. 2017; 2017:8416763. PMid: 28819546 PMCid: PMC5551541. https://doi.org/10.1155/2017/8416763 DOI: https://doi.org/10.1155/2017/8416763
Liou GY, Storz P. Reactive oxygen species in cancer. Free Radic Res. 2010; 44(5):479–96. PMid: 20370557 PMCid: PMC3880197. https://doi.org/10.3109/10715761003667554 DOI: https://doi.org/10.3109/10715761003667554
Aravilli RK, Vikram SL, Kohila V. Phytochemicals as potential antidotes for targeting NF-κB in rheumatoid arthritis. 3 Biotech. 2017; 7(4):253. PMid: 28721679 PMCid: PMC5515733. https://doi.org/10.1007/s1320 5-017-0888-1 DOI: https://doi.org/10.1007/s13205-017-0888-1
Hseu YC, Wu FY, Wu JJ, et al. Anti-inflammatory potential of Antrodia Camphorata through inhibition of iNOS, COX-2 and cytokines via the NF-kappa B pathway. Int Immunopharmacol. 2005; 5(13-14):1914–25. PMid: 16275626. https://doi.org/10.1016/j.intimp. 2005.06.013 DOI: https://doi.org/10.1016/j.intimp.2005.06.013
Hajhashemi V, Vaseghi G, Pourfarzam M, Abdollahi A. Are antioxidants helpful for disease prevention? Res Pharm Sci. 2010; 5(1):1-8. PMCID: PMC3093095.
Sheweita SA, Tilmisany AK. Cancer and phase II drug-metabolizing enzymes. Curr Drug Metab. 2003; 4(1):45-58. PMid: 12570745. https://doi.org/10.2174/1389200033336919 DOI: https://doi.org/10.2174/1389200033336919
Iqbal AJ, Fisher EA, Greaves DR. Inflammation-a critical appreciation of the role of myeloid cells. Microbiol Spectr. 2016; 4(5). https://doi.org/10.1128/microbiolspec.MCHD-0027-2016 DOI: https://doi.org/10.1128/microbiolspec.MCHD-0027-2016
Oluwatobi TS, Adeyinka HA, Idowu KA, Muslimot AT, Mulikat OO. Diallyl disulfide, a garlic-rich compound ameliorates trichloromethane-induced renal oxidative stress, NFkB activation and apoptosis in rats. Clin Nutr Exp. 2019; 23: 44–59. https://doi.org/10.1016/j.yclnex.2018.10.007 DOI: https://doi.org/10.1016/j.yclnex.2018.10.007
Ji H, Cao R, Yang Y, Zhang Y, Iwamoto H, Lim S, Nakamura M, Andersson P, Wang J, Sun Y, Dissing S, He X, Yang X, Cao Y. TNFR1 mediates TNF-α- induced tumour lymphangiogenesis and metastasis by modulating VEGF-C-VEGFR3 signalling. Nat Commun. 2014; 5:4944. PMid: 25229256. https://doi.org/10.1038/ncomms5944 DOI: https://doi.org/10.1038/ncomms5944
Fernandes ES, Passos GF, Medeiros R, da Cunha FM, Ferreira J, Campos MM, Pianowski, LF, Calixto JB. Anti-inflammatory effects of compounds alphahumulene and (-)-trans-caryophyllene isolated from the essential oil of Cordia verbenacea. Eur J Pharmacol. 2007; 569(3):228–36. PMid: 17559833. https://doi.org/10.1016/j.ejphar.2007.04.059 DOI: https://doi.org/10.1016/j.ejphar.2007.04.059
Liu M, Wu W, Li H, Li S, Huang LT, Yang YQ, Sun Q, Wang CX, Yu Z, & Hang CH. Necroptosis, a novel type of programmed cell death, contributes to early neural cells damage after spinal cord injury in adult mice. J Spinal Cord Med. 2015; 38(6):745–53. PMid: 24970278 PMCid: PMC4725808. https://doi.org/10.1179/2045772314Y.0000000224 DOI: https://doi.org/10.1179/2045772314Y.0000000224
Vinothkumar V, Manoharan S, Sindhu G, Nirmal MR, Vetrichelvi V. Geraniol modulates cell proliferation, apoptosis, inflammation and angiogenesis during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. Mol Cell Biochem. 2012; 369(1-2):17–25. PMid: 22729742. https://doi.org/10.1007/s11010-012-1364-1 DOI: https://doi.org/10.1007/s11010-012-1364-1
Perveen S. Introductory chapter: Terpenes and Terpenoids, Terpenes and Terpenoids, Shagufta Perveen and Areej Al-Taweel, IntechOpen, 2018. https://doi.org/10.5772/intechopen.79683 DOI: https://doi.org/10.5772/intechopen.79683
Kuo YH, Kuo YJ, Yu AS, Wu MD, Ong CW, Yang Kuo LM, Huang JT, Chen CF, Li SY. Two novel sesquiterpene lactones, cytotoxic vernolide-A and -B, from Vernonia cinerea. Chem Pharm Bull (Tokyo). 2003; 51(4):425–6. PMid: 12672998. https://doi.org/10.1248/cpb.51.425 DOI: https://doi.org/10.1248/cpb.51.425
Zhang S, Won YK, Ong CN, Shen HM. Anti-cancer potential of sesquiterpene lactones: Bioactivity and molecular mechanisms. Curr Med Chem Anticancer Agents. 2005; 5(3):239-–49. PMid: 15992352. https://doi.org/10.2174/1568011053765976 DOI: https://doi.org/10.2174/1568011053765976
Yang M, Lv Y, Tian X, Lou J, An R, Zhang Q, Li M, Xu L, Dong Z. Neuroprotective effect of β-Caryophyllene on cerebral ischemia-reperfusion injury via regulation of necroptotic neuronal death and inflammation: in vivo and in vitro. Front Neurosci. 2017; 11:583. PMid: 29123466 PMCid: PMC5662640. https://doi. org/10.3389/fnins.2017.00583 DOI: https://doi.org/10.3389/fnins.2017.00583
Fidyt K, Fiedorowicz A, Strzć…daÅ‚a L, Szumny A. β-caryophyllene and β-caryophyllene oxide-natural compounds of anticancer and analgesic properties. Cancer Med. 2016; 5(10):3007–17. PMid: 27696789 PMCid: PMC5083753. https://doi.org/10.1002/cam4.816 DOI: https://doi.org/10.1002/cam4.816
Yang CH, Huang YC, Tsai ML, et al. Inhibition of melanogenesis by β-caryophyllene from lime mint essential oil in mouse B16 melanoma cells. Int J Cosmet Sci. 2015; 37(5):550–4. PMid: 25819153. https://doi.org/10.1111/ics.12224 DOI: https://doi.org/10.1111/ics.12224
Bahi A, Al Mansouri S, Al Memari E, Al Ameri M, Nurulain SM, Ojha S. β-Caryophyllene, a CB2 receptor agonist produces multiple behavioral changes relevant to anxiety and depression in mice. Physiol Behav. 2014; 135:119–24. PMid: 24930711. https://doi.org/10.1016/j.physbeh.2014.06.003 DOI: https://doi.org/10.1016/j.physbeh.2014.06.003
Basha RH, Sankaranarayanan C. β-Caryophyllene, a natural sesquiterpene lactone attenuates hyperglycemia mediated oxidative and inflammatory stress in experimental diabetic rats. Chem Biol Interact. 2016; 245:50–8. PMid: 26748309. https://doi.org/10.1016/j.cbi.2015.12.019 DOI: https://doi.org/10.1016/j.cbi.2015.12.019
Baldissera MD, Souza CF, Grando TH, Stefani LM, Monteiro SG. β-caryophyllene reduces atherogenic index and coronary risk index in hypercholesterolemic rats: The involvement of cardiac oxidative damage. Chem Biol Interact. 2017; 270:9–14. PMid: 28411027. https://doi.org/10.1016/j.cbi.2017.04.008 DOI: https://doi.org/10.1016/j.cbi.2017.04.008
Skold M, Karlberg AT, Matura M, Borje A. The fragrance chemical beta-caryophyllene-air oxidation and skin sensitization. Food Chem Toxicol. 2006; 44(4):538–45. PMid: 16226832. https://doi.org/10.1016/j.fct.2005.08.028 DOI: https://doi.org/10.1016/j.fct.2005.08.028
Kim BH, Yi EH, Ye SK. Signal transducer and activator of transcription 3 as a therapeutic target for cancer and the tumor microenvironment. Arch Pharm Res. 2016; 39(8):1085–99. PMid: 27515050. https://doi.org/10.1007/s12272-016-0795-8 DOI: https://doi.org/10.1007/s12272-016-0795-8
Bento AF, Marcon R, Dutra RC, Claudino RF, Cola M, Leite DF, Calixto JB. β-Caryophyllene inhibits dextran sulfate sodium-induced colitis in mice through CB2 receptor activation and PPARγ pathway. Am J Pathol. 2011; 178(3):1153–66. PMid: 21356367 PMCid: PMC3070571. https://doi.org/10.1016/j.ajpath.2010.11.052 DOI: https://doi.org/10.1016/j.ajpath.2010.11.052
Annese V, Rogai F, Settesoldi A, Bagnoli S. PPARγ in Inflammatory Bowel Disease. PPAR Res. 2012; 2012:620839. PMid: 22997506 PMCid: PMC3444923. https://doi.org/10.1155/2012/620839 DOI: https://doi.org/10.1155/2012/620839
Jung JI, Kim EJ, Kwon GT, Jung YJ, Park T, Kim Y, Yu R, Choi MS, Chun HS, Kwon SH, Her S, Lee KW, Park JH. β-Caryophyllene potently inhibits solid tumor growth and lymph node metastasis of B16F10 melanoma cells in high-fat diet-induced obese C57BL/6N mice. Carcinogenesis. 2015; 36(9):1028–39. PMid: 26025912. https://doi.org/10.1093/carcin/bgv076 DOI: https://doi.org/10.1093/carcin/bgv076
Meng XY, Zhang HX, Mezei M, Cui M. Molecular docking: A powerful approach for structure-based drug discovery. Curr Comput Aided Drug Des. 2011; 7(2):146–57. PMid: 21534921 PMCid: PMC3151162. https://doi.org/10.2174/157340911795677602 DOI: https://doi.org/10.2174/157340911795677602
Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001; 46(1-3):3–26. https://doi.org/10.1016/S0169-409X(00)00129-0 DOI: https://doi.org/10.1016/S0169-409X(96)00423-1
Schwartz JL, Shklar G. Glutathione inhibits experimental oral carcinogenesis, p53 expression and angiogenesis. Nutr Cancer. 1996; 26(2):229–36. PMid: 8875560. https://doi.org/10.1080/01635589609514479 DOI: https://doi.org/10.1080/01635589609514479
Babukumar S, Vinothkumar V, Velu P, Ramachandhiran D, Ramados Nirmal M. Molecular effects of hesperetin, a citrus flavanone on7,12 dimethylbenz(a)anthracene induced buccal pouch squamous cell carcinoma in golden Syrian hamsters. Arch Physiol Biochem. 2017: 123(4):265–78. PMid: 28457144. https://doi.org/10.1080/13813455.2017.1317815 DOI: https://doi.org/10.1080/13813455.2017.1317815
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193(1):265–75. https://pubmed. ncbi.nlm.nih.gov/14907713/ https://doi.org/10.1016/S0021-9258(19)52451-6 DOI: https://doi.org/10.1016/S0021-9258(19)52451-6
Omura T, Sato R. The carbon monoxide-binding pigment of liver microsomes. II. solubilization, purification and properties. J Biol Chem. 1964; 239:2379–85. https://pubmed.ncbi.nlm.nih.gov/14209972/ https://doi.org/ 10.1016/S0021-9258(20)82245-5 DOI: https://doi.org/10.1016/S0021-9258(20)82245-5
Lind C, Cadenas E, Hochstein P, Ernster L. DT-diaphorase: purification, properties and function. Methods Enzymol. 1990; 186:287–301. https://doi.org/10.1016/0076-6879(90)86122-C DOI: https://doi.org/10.1016/0076-6879(90)86122-C
Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem. 1974; 249(22):7130–9. https://pubmed.ncbi.nlm.nih.gov/4436300/ https://doi.org/10.1016/S0021-9258(19)42083-8 DOI: https://doi.org/10.1016/S0021-9258(19)42083-8
Carlberg I, Mannervik B. Glutathione reductase. Methods Enzymol. 1985; 113:484–90. https://doi.org/10.1016/S0076-6879(85)13062-4 DOI: https://doi.org/10.1016/S0076-6879(85)13062-4
Anderson ME. Determination of glutathione and glutathione disulfide in biological samples. Methods Enzymol. 1985; 113:548–55. https://doi.org/10.1016/S0076-6879(85)13073-9 DOI: https://doi.org/10.1016/S0076-6879(85)13073-9
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979; 95(2):351–8. https://doi.org/10.1016/0003-2697(79)90738-3 DOI: https://doi.org/10.1016/0003-2697(79)90738-3
Jiang ZY, Hunt JV, Wolff SP. Ferrous ion oxidation in the presence of xylenol orange for detection of lipid hydroperoxide in low density lipoprotein. Anal Biochem. 1992; 202(2):384–9. https://doi.org/10.1016/0003-2697(92)90122-N DOI: https://doi.org/10.1016/0003-2697(92)90122-N
Rao KS, Recknagel RO. Early onset of lipoperoxidation in rat liver after carbon tetrachloride administration. Exp Mol Pathol. 1968; 9(2):271–8. https://doi.org/10.1016/0014-4800(68)90041-5 DOI: https://doi.org/10.1016/0014-4800(68)90041-5
Kakkar P, Das B, Viswanathan PN. A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys. 1984; 21(2):130–2. https://pubmed.ncbi.nlm.nih.gov/6490072/
Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: biochemical role as a component of glutathione peroxidase. Science. 1973; 179(4073):588–90. PMid: 4686466. https://doi.org/10.1126/science.179.4073.588 DOI: https://doi.org/10.1126/science.179.4073.588
Sinha AK. Colorimetric assay of catalase. Anal Biochem. 1972; 47(2):389–94. https://doi.org/10.1016/0003-26 97(72)90132-7 DOI: https://doi.org/10.1016/0003-2697(72)90132-7
Beutler E, Kelly BM. The effect of sodium nitrite on red cell GSH. Experientia. 1963; 19:96–7. PMid: 13967892. https://doi.org/10.1007/BF02148042 DOI: https://doi.org/10.1007/BF02148042
Desai ID. Vitamin E analysis methods for animal tissues. Methods Enzymol. 1984; 105:138–47. https://doi.org/10.1016/S0076-6879(84)05019-9 DOI: https://doi.org/10.1016/S0076-6879(84)05019-9
Palan PR, Mikhail MS, Basu J, Romney SL. Plasma levels of antioxidant beta-carotene and alphatocopherol in uterine cervix dysplasias and cancer. Nutr Cancer. 1991; 15(1):13–20. PMid: 2017395. https://doi.org/10.1080/01635589109514106 DOI: https://doi.org/10.1080/01635589109514106
Ribeiro FC, Silva JCP, Santos JL KCS. Pontes Diagnóstico da pneumonia enzoóticasuína pela técnica da immunoperoxidase. Arq. Bras. Med. Vet. Zootec. 2004; 56(6):709–14. https://doi.org/10.1590/S0102-09352004000600003 DOI: https://doi.org/10.1590/S0102-09352004000600003
Gillison ML. Current topics in the epidemiology of oral cavity and oropharyngeal cancers. Head Neck. 2007; 29(8):779–92. PMid: 17230556. https://doi.org/10.1002/hed.20573 DOI: https://doi.org/10.1002/hed.20573
Moorthy B, Chu C, Carlin DJ. Polycyclic aromatic hydrocarbons: From metabolism to lung cancer. Toxicol Sci. 2015; 145(1):5–15. PMid: 25911656 PMCid: PMC4408964. https://doi.org/10.1093/toxsci/kfv040 DOI: https://doi.org/10.1093/toxsci/kfv040
Ramachandhiran D, Vinothkumar V, Babukumar S. Paeonol exhibits anti-tumor effects by apoptotic and anti-inflammatory activities in 7,12-dimethylbenz(a) anthracene induced oral carcinogenesis. Biotech Histochem. 2019: 94(1):10–25. PMid: 30101628. https://doi.org/10.1080/10520295.2018.1493221 DOI: https://doi.org/10.1080/10520295.2018.1493221
Velu P, Vinothkumar V, Babukumar S, Ramachandhiran D. Chemopreventive effect of syringic acid on 7,12-dimethylbenz(a)anthracene induced hamster buccal pouch carcinogenesis. Toxicol Mech Methods. 2017; 27(8):631–40. PMid: 28671029. https://doi.org/10.1080/15376516.2017.1349227 DOI: https://doi.org/10.1080/15376516.2017.1349227
Casto BC, Knobloch TJ, Galioto RL, Yu Z, Accurso BT, Warner BM. Chemoprevention of oral cancer by lyophilized strawberries. Anticancer Res. 2013; 33(11):4757–66. https://pubmed.ncbi.nlm.nih.gov/24 222110/
Tanaka T. Chemoprevention of oral carcinogenesis. Eur J Cancer B Oral Oncol. 1995; 31B(1):3–15. https:// doi.org/10.1016/0964-1955(94)00026-Z DOI: https://doi.org/10.1016/0964-1955(94)00026-Z
Androutsopoulos VP, Tsatsakis AM, Spandidos DA. Cytochrome P450 CYP1A1: Wider roles in cancer progression and prevention. BMC Cancer. 2009; 9:187. PMid: 19531241 PMCid: PMC2703651. https://doi.org/10.1186/1471-2407-9-187 DOI: https://doi.org/10.1186/1471-2407-9-187
Zheng GQ, Kenney PM, Lam LK. Sesquiterpenes from clove (Eugenia caryophyllata) as potential anticarcinogenic agents. J Nat Prod. 1992; 55(7):999– 1003. PMid: 1402962. https://doi.org/10.1021/np50 085a029 DOI: https://doi.org/10.1021/np50085a029
Di Sotto A, Mazzanti G, Carbone F, Hrelia P, Maffei F. Inhibition by beta-caryophyllene of ethyl methanesulfonate-induced clastogenicity in cultured human lymphocytes. Mutat Res. 2010; 699(1- 2):23–8. PMid: 20398787. https://doi.org/10.1016/j.mrgentox.2010.04.008 DOI: https://doi.org/10.1016/j.mrgentox.2010.04.008
Bhattacharyya A, Chattopadhyay R, Mitra S, Crowe SE. Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol Rev. 2014; 94(2):329–54. PMid: 24692350 PMCid: PMC4044300. https://doi.org/10.1152/physrev.00040.2012 DOI: https://doi.org/10.1152/physrev.00040.2012
Ayala A, Munoz MF, Argüelles S. Lipid peroxidation: production, metabolism and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev. 2014; 2014:360438. PMid: 24999379 PMCid: PMC4066722. https://doi.org/10.1155/2014/360438 DOI: https://doi.org/10.1155/2014/360438
Racchi ML. Antioxidant defenses in plants with attention to prunus and citrus spp. Antioxidants (Basel). 2013; 2(4):340–69. PMid: 26784469 PMCid: PMC4665512. https://doi.org/10.3390/antiox2040340 DOI: https://doi.org/10.3390/antiox2040340
Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health. J Nutr. 2004; 134(3):489–92. PMid: 14988435. https://doi.org/10.1093/jn/134.3.489 DOI: https://doi.org/10.1093/jn/134.3.489
Singh U, Devaraj S, Jialal I. Vitamin E, oxidative stress and inflammation. Annu Rev Nutr. 2005; 25:151–74. PMid: 16011463. https://doi.org/10.1146/annurev.nut r.24.012003.132446 DOI: https://doi.org/10.1146/annurev.nutr.24.012003.132446
Kurutas EB. The importance of antioxidants which play the role in cellular response against oxidative/ nitrosative stress: Current state. Nutr J. 2016; 15(1):71. PMid: 27456681 PMCid: PMC4960740. https://doi.org/10.1186/s12937-016-0186-5 DOI: https://doi.org/10.1186/s12937-016-0186-5
Grigorescu R, Gruia MI, Nacea V, Nitu C, Negoita V, Glavan D. The evaluation of non-enzymatic antioxidants effects in limiting tumor-associated oxidative stress, in a tumor rat model. J Med Life. 2015; 8(4):513–6. https://pubmed.ncbi.nlm.nih.gov/26664481/
Ames-Sibin AP, Barizí£o C L, Castro-Ghizoni CV, Silva F, Sa-Nakanishi AB, Bracht L, Bersani- Amado CA, Marcal-Natali MR, Bracht A, Comar JF. β-Caryophyllene, the major constituent of copaiba oil, reduces systemic inflammation and oxidative stress in arthritic rats. J Cell Biochem. 2018; 119(12):10262–77. PMid: 30132972. https://doi.org/10.1002/jcb.27369 DOI: https://doi.org/10.1002/jcb.27369
Tan BL, Norhaizan ME, Liew WP, Sulaiman Rahman H. Antioxidant and oxidative stress: A mutual interplay in age-related diseases. Front Pharmacol. 2018; 9:1162. PMid: 30405405 PMCid: PMC6204759. https://doi.org/10.3389/fphar.2018.01162 DOI: https://doi.org/10.3389/fphar.2018.01162
Fuccelli R, Fabiani R, Rosignoli P. Hydroxytyrosol exerts anti-inflammatory and anti-oxidant activities in a mouse model of systemic inflammation. Molecules. 2018; 23(12):3212. PMid: 30563131 PMCid: PMC6321432. https://doi.org/10.3390/molec ules23123212 DOI: https://doi.org/10.3390/molecules23123212
Pant A, Mishra V, Saikia SK, Shukla V, Asthana J, Akhoon BA, Pandey R. Beta-caryophyllene modulates expression of stress response genes and mediates longevity in Caenorhabditis elegans. [Published correction appears in Exp Gerontol. 2016 Dec 1;85:128]. Exp Gerontol. 2014; 57:81–95. PMid: 24835194. https://doi.org/10.1016/j.exger.2014.05.007 DOI: https://doi.org/10.1016/j.exger.2014.05.007
Ojha S, Javed H, Azimullah S, Haque ME. β-Caryophyllene, a phytocannabinoid attenuates oxidative stress, neuroinflammation, glial activation and salvages dopaminergic neurons in a rat model of Parkinson disease. Mol Cell Biochem. 2016; 418(1- 2):59–70. PMid: 27316720. https://doi.org/10.1007/ s11010-016-2733-y DOI: https://doi.org/10.1007/s11010-016-2733-y
Yamaguchi M, Levy RM. The combination of β-caryophyllene, baicalin and catechin synergistically suppresses the proliferation and promotes the death of RAW267.4 macrophages in vitro. Int J Mol Med. 2016; 38(6):1940–6. PMid: 27840942. https://doi.org/10.3892/ijmm.2016.2801 DOI: https://doi.org/10.3892/ijmm.2016.2801
Sain S, Naoghare PK, Devi SS, Daiwile A, Krishnamurthi K, Arrigo P, Chakrabarti T. Beta caryophyllene and caryophyllene oxide, isolated from Aegle marmelos, as the potent anti-inflammatory agents against lymphoma and neuroblastoma cells. Antiinflamm Antiallergy Agents Med Chem. 2014; 13(1):45–55. PMid: 24484210. https://doi.org/10.2174/18715230113129990016 DOI: https://doi.org/10.2174/18715230113129990016
Kuwahata H, Katsuyama S, Komatsu T, Nakamura H, Corasaniti M, Bagetta G, Sakurada S, Sakurada T, Takahama, K. Local Peripheral Effects of β-Caryophyllene through CB2 Receptors in Neuropathic Pain in Mice. J Pharm Pharmacol. 2012; 3(4):397–403. https://doi.org/10.4236/pp.2012.34053 DOI: https://doi.org/10.4236/pp.2012.34053
Ramachandhiran D, Sankaranarayanan C, Murali R, Babukumar S, Vinothkumar V. β-Caryophyllene promotes oxidative stress and apoptosis in KB cells through activation of mitochondrial-mediated pathway - An in-vitro and in-silico study. Arch Physiol Biochem. 2019; 1–15. PMid: 31583906. https://doi.org/10.1080/13813455.2019.1669057 DOI: https://doi.org/10.1080/13813455.2019.1669057
Dahham SS, Tabana YM, Khadeer Ahamed MB, Abdul Majid AMS. In vivo anti-inflammatory activity of β-caryophyllene, evaluated by molecular imaging. Mol Med Chem. 2015: 2015 1: e1001. https://doi.org/10.14800/mmc.1001 DOI: https://doi.org/10.14800/mmc.1001
Ozaki T, Nakagawara A. Role of p53 in cell death and human cancers. Cancers (Basel). 2011; 3(1):994–1013. PMid: 24212651 PMCid: PMC3756401. https://doi.org/10.3390/cancers3010994 DOI: https://doi.org/10.3390/cancers3010994
Sionov RV, Haupt Y. The cellular response to p53: The decision between life and death. Oncogene. 1999; 18(45):6145–57. PMid: 10557106. https://doi.org/10.1038/sj.onc.1203130 DOI: https://doi.org/10.1038/sj.onc.1203130
Vousden KH, Lu X. Live or let die: The cell's response to p53. Nat Rev Cancer. 2002; 2(8):594–604. PMid: 12154352. https://doi.org/10.1038/nrc864 DOI: https://doi.org/10.1038/nrc864
Chang KW, Lin SC, Koos S, Pather K, Solt D. p53 and Ha-ras mutations in chemically induced hamster buccal pouch carcinomas. Carcinogenesis. 1996; 17(3):595–600. PMid: 8631150. https://doi.org/10.1093/carcin/17.3.595 DOI: https://doi.org/10.1093/carcin/17.3.595
Amiel E, Ofir R, Dudai N, Soloway E, Rabinsky T, Rachmilevitch S. β-Caryophyllene, a compound isolated from the biblical balm of gilead (Commiphora gileadensis), is a selective apoptosis inducer for tumor cell lines. Evid Based Complement Alternat Med. 2012; 2012:872394. PMid: 22567036 PMCid: PMC3332194. https://doi.org/10.1155/2012/872394 DOI: https://doi.org/10.1155/2012/872394
Moon SM, Kim SA, Yoon JH, Ahn SG. HOXC6 is deregulated in human head and neck squamous cell carcinoma and modulates Bcl-2 expression. J Biol Chem. 2012; 287(42):35678-35688. PMid: 22896703 PMCid: PMC3471680. https://doi.org/10.1074/jbc.M112.361675 DOI: https://doi.org/10.1074/jbc.M112.361675
Xu DC, Arthurton L, Baena-Lopez LA. Learning on the Fly: The interplay between caspases and cancer. Biomed Res Int. 2018; 2018:5473180. PMid: 29854765 PMCid: PMC5949197. https://doi.org/10.1155/2018/5473180 DOI: https://doi.org/10.1155/2018/5473180
Bratton SB, Salvesen GS. Regulation of the Apaf- 1-caspase-9 apoptosome. J Cell Sci. 2010; 123(Pt 19):3209–14. PMid: 20844150 PMCid: PMC2939798. https://doi.org/10.1242/jcs.073643 DOI: https://doi.org/10.1242/jcs.073643
Sander T, Liljefors T, Balle T. Prediction of the receptor conformation for iGluR2 agonist binding: QM/MM docking to an extensive conformational ensemble generated using normal mode analysis. J Mol Graph Model. 2008; 26(8):1259–68. PMid: 18203639. https://doi.org/10.1016/j.jmgm.2007.11.006 DOI: https://doi.org/10.1016/j.jmgm.2007.11.006
Fu Y, Zhao J, Chen Z. Insights into the molecular mechanisms of protein-ligand interactions by molecular docking and molecular dynamics simulation: A case of oligopeptide binding protein. Comput Math Methods Med. 2018; 2018:3502514. PMid: 30627209 PMCid: PMC6305025. https://doi.org/10.1155/2018/3502514 DOI: https://doi.org/10.1155/2018/3502514
Pillai LS, Nair BR. Molecular docking studies using Sinigrin and Tamoxifen. J Pharmacogn Phytochem. 2018; 7(2):3217–21. https://www.phytojournal.com/ archives/?year=2018&vol=7&issue=2&ArticleId=4021
