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


  • Annamalai University, Department of Biochemistry and Biotechnology, Faculty of Science, Annamalainagar, Tamil Nadu, 608002, India


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.


Antioxidant, Apoptosis, β-caryophyllene, Detoxification Enzymes, DMBA, Oral Cancer

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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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Fidyt K, Fiedorowicz A, Strządała 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Carlberg I, Mannervik B. Glutathione reductase. Methods Enzymol. 1985; 113:484–90. 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

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

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

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

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

Sinha AK. Colorimetric assay of catalase. Anal Biochem. 1972; 47(2):389–94. https://doi.org/10.1016/0003-26 97(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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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, Barizão 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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