β-caryophyllene and β-caryophyllene oxide—natural compounds of anticancer and analgesic properties

Cancer Medicine

Volumn 5, Issue 10, 2016, Pages 3007-3017

  Fidyt, Klaudyna ^a,b   Fiedorowicz, Anna ^a   Strządała, Leon ^a   Szumny, Antoni ^b  

^a INSTITUTE OF IMMUNOLOGY AND EXPERIMENTAL THERAPY   (Poland)

^b WROC AW UNIVERSITY OF ENVIRONMENTAL AND LIFE SCIENCES   (Poland)

Author keywords

Analgesic; anticancer; antinociception; cannabinoid receptor type 2 (CB2); caryophyllene (BCP); caryophyllene oxide (BCPO)

Indexed keywords

CANNABINOID 1 RECEPTOR; CANNABINOID 2 RECEPTOR; CARYOPHYLLENE; CARYOPHYLLENE OXIDE; DOXORUBICIN; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE; PACLITAXEL; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; S6 KINASE; STAT3 PROTEIN; ANALGESIC AGENT; ANTINEOPLASTIC AGENT; CANNABINOID RECEPTOR; SESQUITERPENE;

ANALGESIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTINOCICEPTION; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; BINDING AFFINITY; CANCER CELL LINE; CANCER INHIBITION; CANCER MODEL; CANCER PAIN; CHRONIC PAIN; CONCENTRATION RESPONSE; DRUG CYTOTOXICITY; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENTIATION; DRUG PROTEIN BINDING; DRUG STRUCTURE; EVIDENCE BASED MEDICINE; GENE EXPRESSION; HUMAN; IC50; NEUROPATHIC PAIN; NONHUMAN; PAIN; PRIORITY JOURNAL; REVIEW; ANIMAL; CELL PROLIFERATION; CELL SURVIVAL; DRUG EFFECTS; DRUG SCREENING; METABOLISM; SIGNAL TRANSDUCTION;

ANALGESICS; ANIMALS; ANTINEOPLASTIC AGENTS, PHYTOGENIC; CELL PROLIFERATION; CELL SURVIVAL; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; RECEPTORS, CANNABINOID; SESQUITERPENES; SIGNAL TRANSDUCTION;

EID: 84990064132     PISSN: None     EISSN: 20457634     Source Type: Journal    
DOI: 10.1002/cam4.816     Document Type: Review

References (68)

1. Sarpietro, M. G., A. Di Sotto, M. L. Accolla, and F. Castelli. 2015. Interaction of β-caryophyllene and β-caryophyllene oxide with phospholipid bilayers: differential scanning calorimetry study. Thermochim. Acta 600:28–34. doi:10.1016/j.tca.2014.11.029.
2. Medeiros, R., G. F. Passos, C. E. Vitor, J. Koepp, T. L. Mazzuco, L. F. Pianowski, et al. 2007. Effect of two active compounds obtained from the essential oil of Cordia verbenacea on the acute inflammatory responses elicited by LPS in the rat paw. Br. J. Pharmacol. 151:618–627. doi:10.1038/sj.bjp.0707270.
3. Langhasova, L., V. Hanusova, J. Rezek, B. Stohanslova, M. Ambroz, V. Kralova, et al. 2014. Essential oil from Myrica rubra leaves inhibits cancer cell proliferation and induces apoptosis in several human intestinal lines. Ind. Crops Prod. 59:20–26. doi:10.1016/j.indcrop.2014.04.018.
4. Sabulal, B., M. Dan, R. Kurup, N. S. Pradeep, R. K. Valsamma, and V. George. 2006. Caryophyllene-rich rhizome oil of Zingiber nimmonii from South India: chemical characterization and antimicrobial activity. Phytochemistry 67:2469–2473. doi:10.1016/j.phytochem.2006.08.003.
5. Singh, G., P. Marimuthu, C. S. de Heluani, and C. A. Catalan. 2006. Antioxidant and biocidal activities of Carum nigrum (seed) essential oil, oleoresin, and their selected components. J. Agric. Food Chem. 54:174–181. doi:10.1021/jf0518610.
6. Klauke, A.-L., I. Racz, B. Pradier, A. Markert, A. Zimmer, J. Gertsch, et al. 2014. The cannabinoid CB 2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain. Eur. Neuropsychopharmacol. 24:608–620. doi:10.1016/j.euroneuro.2013.10.008.
7. Tung, Y.-T., M.-T. Chua, S.-Y. Wang, and S.-T. Chang. 2008. Anti-inflammation activities of essential oil and its constituents from indigenous cinnamon (Cinnamomum osmophloeum) twigs. Bioresour. Technol. 99:3908–3913. doi:10.1016/j.biortech.2007.07.050.
8. Hammami, S., H. Jmii, R. E. Mokni, A. Khmiri, K. Faidi, H. Dhaouadi, et al. 2015. Essential Oil Composition, Antioxidant, Cytotoxic and Antiviral Activities of Teucrium pseudochamaepitys Growing Spontaneously in Tunisia. Molecules 20:20426–20433. doi:10.3390/molecules201119707.
9. Zheng, G.-Q., P. M. Kenney, and L. K. Lam. 1992. Sesquiterpenes from clove (Eugenia caryophyllata) as potential anticarcinogenic agents. J. Nat. Prod. 55:999–1003. doi:10.1021/np50085a029.
10. Singh, T. P., R. K. Singh, and P. Malik. 2014. Analgesic and anti-inflammatory activities of Annona squamosa Linn bark. J. Scientific and Innov. Res. 3:60–64.
11. Asakawa, Y., T. Ishida, M. Toyota, and T. Takemoto. 1986. Terpenoid biotransformation in mammals IV Biotransformation of (+)-longifolene,(-)-caryophyllene,(-)-caryophyllene oxide,(-)-cyclocolorenone,(+)-nootkatone,(-)-elemol,(-)-abietic acid and (+)-dehydroabietic acid in rabbits. Xenobiotica 16:753–767.
12. Hart, E., and L. Wong. 1971. Acute oral toxicity studies in rats, acute dermal toxicity and primary skin irritation studies in rabbits of 17 fragrance materials. Bionetics Res. Lab. July 30:1971. Report submitted by EFFA to SCF.
13. Mediavilla, V., and S. Steinemann. 1997. Essential oil of Cannabis sativa L. strains. J. Int. Hemp Assoc. 4:80–82.
14. Gertsch, J., M. Leonti, S. Raduner, I. Racz, J.-Z. Chen, X.-Q. Xie, et al. 2008. Beta-caryophyllene is a dietary cannabinoid. Proc. Natl Acad. Sci. 105:9099–9104. doi:10.1073/pnas.0803601105.
15. Clayton, N., F. Marshall, C. Bountra, and C. O' shaughnessy. 2002. CB1 and CB2 cannabinoid receptors are implicated in inflammatory pain. Pain 96:253–260. doi:10.1016/S0304-3959(01)00454-7.
16. Guzmán, M., and C. Sánchez. 1999. Effects of cannabinoids on energy metabolism. Life Sci. 65:657–664. doi:10.1016/S0024-3205(99)00288-X.
17. Schlicker, E., and M. Kathmann. 2001. Modulation of transmitter release via presynaptic cannabinoid receptors. Trends Pharmacol. Sci. 22:565–572. doi:10.1016/S0165-6147(00)01805-8.
18. Núñez, E., C. Benito, M. R. Pazos, A. Barbachano, O. Fajardo, S. González, et al. 2004. Cannabinoid CB2 receptors are expressed by perivascular microglial cells in the human brain: an immunohistochemical study. Synapse 53:208–213. doi:10.1002/syn.20050.
19. Onaivi, E. S. 2006. Neuropsychobiological evidence for the functional presence and expression of cannabinoid CB2 receptors in the brain. Neuropsychobiology 54:231–246. doi:10.1159/000100778.
20. Pacher, P., and G. Kunos. 2013. Modulating the endocannabinoid system in human health and disease–successes and failures. FEBS J. 280:1918–1943. doi:10.1111/febs.12260.
21. Di Marzo, V. 2008. The endocannabinoid system in obesity and type 2 diabetes. Diabetologia 51:1356–1367. doi:10.1007/s00125-008-1048-2.
22. Galve-Roperh, I., T. Aguado, J. Palazuelos, and M. Guzmán. 2007. The endocannabinoid system and neurogenesis in health and disease. Neuroscientist 13:109–114. doi:10.1177/1073858406296407.
23. Demuth, D. G., and A. Molleman. 2006. Cannabinoid signalling. Life Sci. 78:549–563. doi:10.1016/j.lfs.2005.05.055.
24. Chicca, A., D. Caprioglio, A. Minassi, V. Petrucci, G. Appendino, O. Taglialatela-Scafati, et al. 2014. Functionalization of β-caryophyllene generates novel polypharmacology in the endocannabinoid system. ACS Chem. Biol. 9:1499–1507. doi:10.1021/cb500177c.
25. Carracedo, A., M. Gironella, M. Lorente, S. Garcia, M. Guzmán, G. Velasco, et al. 2006. Cannabinoids induce apoptosis of pancreatic tumor cells via endoplasmic reticulum stress-related genes. Cancer Res. 66:6748–6755. doi:10.1158/0008-5472.CAN-06-0169.
26. Alexander, A., P. F. Smith, and R. J. Rosengren. 2009. Cannabinoids in the treatment of cancer. Cancer Lett. 285:6–12. doi:10.1016/j.canlet.2009.04.005.
27. Casanova, M. L., C. Blázquez, J. Martínez-Palacio, C. Villanueva, M. J. Fernández-Aceñero, J. W. Huffman, et al. 2003. Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors. J. Clin. Invest. 111:43–50. doi:10.1172/JCI200316116.
28. Jun, N. J., A. Mosaddik, J. Y. Moon, K.-C. Jang, D.-S. Lee, K. S. Ahn, et al. 2011. Cytotoxic activity of β-caryophyllene oxide isolated from Jeju Guava (Psidium cattleianum Sabine) leaf. Rec. Nat. Prod. 5:242–246.
29. Shahwar, D., S. Ullah, M. A. Khan, N. Ahmad, A. Saeed, and S. Ullah. 2015. Anticancer activity of Cinnamon tamala leaf constituents towards human ovarian cancer cells. Pak. J.Pharm. Sci. 28:969–972.
30. Dahham, S. S., Y. M. Tabana, M. A. Iqbal, M. B. Ahamed, M. O. Ezzat, A. S. Majid, et al. 2015. The Anticancer, antioxidant and antimicrobial properties of the Sesquiterpene β-Caryophyllene from the essential Oil of Aquilaria crassna. Molecules 20:11808–11829. doi:10.3390/molecules200711808.
31. Ambrož, M., I. Boušová, A. Skarka, V. Hanušová, V. Králová, P. Matoušková, et al. 2015. The influence of sesquiterpenes from Myrica rubra on the antiproliferative and pro-oxidative effects of doxorubicin and Its accumulation in cancer cells. Molecules 20:15343–15358. doi:10.3390/molecules200815343.
32. Legault, J., and A. Pichette. 2007. Potentiating effect of β-caryophyllene on anticancer activity of α-humulene, isocaryophyllene and paclitaxel. J. Pharm. Pharmacol. 59:1643–1647. doi:10.1211/jpp.59.12.0005.
33. Amiel, E., R. Ofir, N. Dudai, E. Soloway, T. Rabinsky, and S. Rachmilevitch. 2012. ß-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. 2012:872394. doi: 10.1155/2012/872394.
34. Jung, J. I., E. J. Kim, G. T. Kwon, Y. J. Jung, T. Park, Y. Kim, et al. 2015. 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 36:1028–1039. doi:10.1093/carcin/bgv076.
35. Dahham, S. S., A. M. Shah, and A. Majid. 2014. β- caryophyllene, a natural sesquiterpene isolated from agar wood inhibits growth and metastasis of human colorectal cancer by modulation of multiple targets in vitro and in vivo. J. Cancer Sci. Ther. 7:10, doi: 10.4172/1948-5956.C1.061.
36. Campos, M. I., W. D. Vieira, C. N. Campos, F. M. Aarestrup, and B. J. Aarestrup. 2015. Atorvastatin and trans-caryophyllene for the prevention of leukopenia in an experimental chemotherapy model in Wistar rats. Mol. Clin. Oncol. 3:825–828.
37. Kim, C., S. K. Cho, K.-D. Kim, D. Nam, W.-S. Chung, H.-J. Jang, et al. 2014. β-Caryophyllene oxide potentiates TNFα-induced apoptosis and inhibits invasion through down-modulation of NF-κB-regulated gene products. Apoptosis 19:708–718. doi:10.1007/s10495-013-0957-9.
38. Zasadil, L. M., K. A. Andersen, D. Yeum, G. B. Rocque, L. G. Wilke, A. J. Tevaarwerk, et al. 2014. Cytotoxicity of paclitaxel in breast cancer is due to chromosome missegregation on multipolar spindles. Sci. Transl. Med. 6:229ra243. doi: 10.1126/scitranslmed.3007965.
39. Sikkema, J., J. De Bont, and B. Poolman. 1994. Interactions of cyclic hydrocarbons with biological membranes. J. Biol. Chem. 269:8022–8028.
40. Park, K.-R., D. Nam, H.-M. Yun, S.-G. Lee, H.-J. Jang, G. Sethi, et al. 2011. β-Caryophyllene oxide inhibits growth and induces apoptosis through the suppression of PI3K/AKT/mTOR/S6K1 pathways and ROS-mediated MAPKs activation. Cancer Lett. 312:178–188. doi:10.1016/j.canlet.2011.08.001.
41. LoPiccolo, J., G. M. Blumenthal, W. B. Bernstein, and P. A. Dennis. 2008. Targeting the PI3K/AKT/mTOR pathway: effective combinations and clinical considerations. Drug Resist. Updates 11:32–50. doi:10.1016/j.drup.2007.11.003.
42. Ryu, N. H., K.-R. Park, S.-M. Kim, H.-M. Yun, D. Nam, S.-G. Lee, et al. 2012. A hexane fraction of guava leaves (Psidium guajava L.) induces anticancer activity by suppressing AKT/mammalian target of rapamycin/ribosomal p70 S6 kinase in human prostate cancer cells. J. Med. Food 15:231–241. doi:10.1089/jmf.2011.1701.
43. Darnell, J. E. 1997. STATs and gene regulation. Science 277:1630–1635. doi:10.1126/science.277.5332.1630.
44. Kim, C., S. K. Cho, S. Kapoor, A. Kumar, S. Vali, T. Abbasi, et al. 2014. β-caryophyllene oxide inhibits constitutive and inducible STAT3 signaling pathway through induction of the SHP-1 protein tyrosine phosphatase. Mol. Carcinog. 53:793–806. doi:10.1002/mc.22035.
45. Naugler, W. E., and M. Karin. 2008. NF-κB and cancer—identifying targets and mechanisms. Curr. Opin. Genet. Dev. 18:19–26. doi:10.1016/j.gde.2008.01.020.
46. Sain, S., P. K. Naoghare, S. Saravana Devi, A. Daiwile, K. Krishnamurthi, P. Arrigo, et al. 2014. 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. 13:45–55, doi: 10.2174/18715230113129990016.
47. Phillips, C. J. 2009. The cost and burden of chronic pain. Rev. Pain 3:2–5. doi:10.1177/204946370900300102.
48. Goldberg, D. S., and S. J. McGee. 2011. Pain as a global public health priority. BMC Public Health 11:770. doi:10.1186/1471-2458-11-770.
49. Keefe, F. J., A. P. Abernethy, L. C Campbell. 2005. Psychological approaches to understanding and treating disease-related pain. Annu. Rev. Psychol. 56:601–630. doi:10.1038/nrrheum.2010.22.
50. Starowicz, K., N. Malek, and B. Przewlocka. 2013. Cannabinoid receptors and pain. Wiley Interdiscip. Rev. Membr Transp. Signal. 2:121–132. doi:10.1002/wmts.83.
51. Murnion, B. 2015. Medicinal cannabis. Aust. Prescr. 38:212–215, doi: 10.18773/austprescr.2015.072.
52. Kuwahata, H., S. Katsuyama, T. Komatsu, H. Nakamura, M. T. Corasaniti, G. Bagetta, et al. 2013. Local Peripheral Effects of β-Caryophyllene through CB 2 Receptors in Neuropathic Pain in Mice. Pharmacol. Pharm. 3:397–403. doi:10.4236/pp.2012.34053.
53. Paula-Freire, L., M. Andersen, V. Gama, G. Molska, and E. Carlini. 2014. The oral administration of trans-caryophyllene attenuates acute and chronic pain in mice. Phytomedicine 21:356–362. doi:10.1016/j.phymed.2013.08.006.
54. Chavan, M., P. Wakte, and D. Shinde. 2010. Analgesic and anti-inflammatory activity of Caryophyllene oxide from Annona squamosa L. bark. Phytomedicine 17:149–151. doi:10.1016/j.phymed.2009.05.016.
55. Golshani, S., F. Karamkhani, H. R. Monsef-Esfehani, and M. Abdollahi. 2004. Antinociceptive effects of the essential oil of Dracocephalum kotschyi in the mouse writhing test. J. Pharm. Pharm. Sci. 7:76–79.
56. Menezes, I. A., M. S. Marques, T. C. Santos, K. S. Dias, A. B. Silva, I. C. Mello, et al. 2007. Antinociceptive effect and acute toxicity of the essential oil of Hyptis fruticosa in mice. Fitoterapia 78:192–195. doi:10.1016/j.fitote.2006.11.020.
57. Shah, S. M. M., F. Ullah, S. M. H. Shah, M. Zahoor, and A. Sadiq. 2012. Analysis of chemical constituents and antinociceptive potential of essential oil of Teucrium Stocksianum bioss collected from the North West of Pakistan. BMC Complement. Altern. Med. 12:244. doi:10.1186/1472-6882-12-244.
58. Pinheiro, B., A. Silva, G. Souza, J. Figueiredo, F. Cunha, S. Lahlou, et al. 2011. Chemical composition, antinociceptive and anti-inflammatory effects in rodents of the essential oil of Peperomia serpens (Sw.) Loud. J. Ethnopharmacol. 138:479–486. doi:10.1016/j.jep.2011.09.037.
59. Khalilzadeh, E., G. Vafaei Saiah, H. Hasannejad, A. Ghaderi, S. Ghaderi, G. Hamidian, et al. 2015. Antinociceptive effects, acute toxicity and chemical composition of Vitex agnus-castus essential oil. Avicenna J. Phytomed. 5:218–230.
60. Pdos Menezes, P., A. A. Araujo, G. A. Doria, L. J. Quintans-Junior, M. G. de Oliveira, M. R. dos Santos, et al. 2015. Physicochemical Characterization and Analgesic Effect of Inclusion Complexes of Essential Oil from Hyptis pectinata L. Poit Leaves with β-Cyclodextrin. Curr. Pharm. Biotechnol. 16:440–450. doi:10.2174/1389201015666141202101909.
61. Fiorenzani, P., S. Lamponi, A. Magnani, I. Ceccarelli, and A. M. Aloisi. 2014. In Vitro and In Vivo characterization of the new analgesic combination Beta-caryophyllene and docosahexaenoic acid. Evid. Based Complement. Alternat. Med. 2014:596312, doi: 10.1155/2014/596312.
62. Chapkin, R. S., W. Kim, J. R. Lupton, and D. N. McMurray. 2009. Dietary docosahexaenoic and eicosapentaenoic acid: emerging mediators of inflammation. Prostaglandins Leukot. Essent. Fatty Acids 81:187–191. doi:10.1016/j.plefa.2009.05.010.
63. Anand, U., W. R. Otto, D. Sanchez-Herrera, P. Facer, Y. Yiangou, Y. Korchev, et al. 2008. Cannabinoid receptor CB2 localisation and agonist-mediated inhibition of capsaicin responses in human sensory neurons. Pain 138:667–680. doi:10.1016/j.pain.2008.06.007.
64. Manzanares, J., M. Julian, and A. Carrascosa. 2006. Role of the cannabinoid system in pain control and therapeutic implications for the management of acute and chronic pain episodes. Curr. Neuropharmacol. 4:239–257. doi:10.2174/157015906778019527.
65. Ibrahim, M. M., F. Porreca, J. Lai, P. J. Albrecht, F. L. Rice, A. Khodorova, et al. 2005. CB2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opioids. Proc. Natl Acad. Sci. USA 102:3093–3098. doi:10.1073/pnas.0409888102.
66. Malan, T. P., M. M. Ibrahim, J. Lai, T. W. Vanderah, A. Makriyannis, and F. Porreca. 2003. CB 2 cannabinoid receptor agonists: pain relief without psychoactive effects? Curr. Opin. Pharmacol. 3:62–67. doi:10.1016/S1471-4892(02)00004-8.
67. Fernandes, E. S., G. F. Passos, R. Medeiros, F. M. da Cunha, J. Ferreira, M. M. Campos, et al. 2007. Anti-inflammatory effects of compounds alpha-humulene and (−)-trans-caryophyllene isolated from the essential oil of Cordia verbenacea. Eur. J. Pharmacol. 569:228–236. doi:10.1016/j.ejphar.2007.04.059.
68. Katsuyama, S., H. Mizoguchi, H. Kuwahata, T. Komatsu, K. Nagaoka, H. Nakamura, et al. 2013. Involvement of peripheral cannabinoid and opioid receptors in β-caryophyllene-induced antinociception. Eur. J. Pain 17:664–675. doi:10.1002/j.1532-2149.2012.00242.x.