Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Beta-Caryophyllene Suppresses Ovarian Cancer Proliferation by Inducing Cell Cycle Arrest and Apoptosis

Author(s): Santhosh Arul, Harinee Rajagopalan, Jivitesh Ravi and Haripriya Dayalan*

Volume 20, Issue 13, 2020

Page: [1530 - 1537] Pages: 8

DOI: 10.2174/1871520620666200227093216

Price: $65

Abstract

Background: Ovarian cancer is the fifth most common cause of cancer deaths among women with lesser prognostics. Current treatment options are chemotherapy with platinum and taxane based chemotherapy. β-Caryophyllene (BCP) an essential oil found in many plant species is known to possess an anti-proliferative effect.

Objective: We aimed to investigate the antiproliferative, cytotoxic, and apoptotic role of BCP against ovarian cancer cells PA-1 and OAW 42.

Methods: The antiproliferative effect of BCP was determined by MTT assay and cell viability by trypan blue exclusion assay. Cell cycle and live/dead cell analyses were performed by flow cytometry to determine cell cycle distribution and apoptosis, respectively.

Results: Results of MTT assay proved the anti-proliferative effect of BCP in a dose and time-dependent manner in ovarian cancer cells. Cell cycle analysis showed that BCP induced S Phase arrest in OAW 42 cells. Results of apoptosis assay confirmed the apoptosis inducing potential of BCP in ovarian cancer cells. The apoptosis is mediated by caspase-3 activation and PARP cleavage.

Conclusion: The results of our present study prove that BCP exerts its action partly by inducing cell cycle arrest and apoptosis in ovarian cancer. We conclude that BCP is a potential anti-cancer agent.

Keywords: Beta-caryophyllene, ovarian cancer, cell cycle arrest, apoptosis, PA-1, OAW 42.

Graphical Abstract
[1]
Banks, E. The epidemiology of ovarian cancer. Ovarian Cancer, 2001, 39, 3-11.
[http://dx.doi.org/10.1385/1-59259-071-3:3]
[2]
Bast, R.C., Jr; Hennessy, B.; Mills, G.B. The biology of ovarian cancer: New opportunities for translation. Nat. Rev. Cancer, 2009, 9(6), 415-428.
[http://dx.doi.org/10.1038/nrc2644] [PMID: 19461667]
[3]
Feeley, K.M.; Wells, M. Precursor lesions of ovarian epithelial malignancy. Histopathology, 2001, 38(2), 87-95.
[http://dx.doi.org/10.1046/j.1365-2559.2001.01042.x] [PMID: 11207821]
[4]
Menon, U.; Ryan, A.; Kalsi, J.; Gentry-Maharaj, A.; Dawnay, A.; Habib, M.; Apostolidou, S.; Singh, N.; Benjamin, E.; Burnell, M.; Davies, S.; Sharma, A.; Gunu, R.; Godfrey, K.; Lopes, A.; Oram, D.; Herod, J.; Williamson, K.; Seif, M.W.; Jenkins, H.; Mould, T.; Woolas, R.; Murdoch, J.B.; Dobbs, S.; Amso, N.N.; Leeson, S.; Cruickshank, D.; Scott, I.; Fallowfield, L.; Widschwendter, M.; Reynolds, K.; McGuire, A.; Campbell, S.; Parmar, M.; Skates, S.J.; Jacobs, I. Risk algorithm using serial biomarker measurements doubles the number of screen-detected cancers compared with a single-threshold rule in the United Kingdom collaborative trial of ovarian cancer screening. J. Clin. Oncol., 2015, 33(18), 2062-2071.
[http://dx.doi.org/10.1200/JCO.2014.59.4945] [PMID: 25964255]
[5]
Jacobs, I.J.; Menon, U.; Ryan, A.; Gentry-Maharaj, A.; Burnell, M.; Kalsi, J.K.; Amso, N.N.; Apostolidou, S.; Benjamin, E.; Cruickshank, D.; Crump, D.N.; Davies, S.K.; Dawnay, A.; Dobbs, S.; Fletcher, G.; Ford, J.; Godfrey, K.; Gunu, R.; Habib, M.; Hallett, R.; Herod, J.; Jenkins, H.; Karpinskyj, C.; Leeson, S.; Lewis, S.J.; Liston, W.R.; Lopes, A.; Mould, T.; Murdoch, J.; Oram, D.; Rabideau, D.J.; Reynolds, K.; Scott, I.; Seif, M.W.; Sharma, A.; Singh, N.; Taylor, J.; Warburton, F.; Widschwendter, M.; Williamson, K.; Woolas, R.; Fallowfield, L.; McGuire, A.J.; Campbell, S.; Parmar, M.; Skates, S.J. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): A randomised controlled trial. Lancet, 2016, 387(10022), 945-956.
[http://dx.doi.org/10.1016/S0140-6736(15)01224-6] [PMID: 26707054]
[6]
Ozols, R.F.; Bundy, B.N.; Greer, B.E.; Fowler, J.M.; Clarke-Pearson, D.; Burger, R.A.; Mannel, R.S.; DeGeest, K.; Hartenbach, E.M.; Baergen, R. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: A Gynecologic Oncology Group study. J. Clin. Oncol., 2003, 21(17), 3194-3200.
[http://dx.doi.org/10.1200/JCO.2003.02.153] [PMID: 12860964]
[7]
Vasey, P.A.; Jayson, G.C.; Gordon, A.; Gabra, H.; Coleman, R.; Atkinson, R.; Parkin, D.; Paul, J.; Hay, A.; Kaye, S.B. Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J. Natl. Cancer Inst., 2004, 96(22), 1682-1691.
[http://dx.doi.org/10.1093/jnci/djh323] [PMID: 15547181]
[8]
du Bois, A.; Lück, H-J.; Meier, W.; Adams, H-P.; Möbus, V.; Costa, S.; Bauknecht, T.; Richter, B.; Warm, M.; Schröder, W.; Olbricht, S.; Nitz, U.; Jackisch, C.; Emons, G.; Wagner, U.; Kuhn, W.; Pfisterer, J. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J. Natl. Cancer Inst., 2003, 95(17), 1320-1329.
[http://dx.doi.org/10.1093/jnci/djg036] [PMID: 12953086]
[9]
Matulonis, U.A.; Sood, A.K.; Fallowfield, L.; Howitt, B.E.; Sehouli, J.; Karlan, B.Y. Ovarian cancer. Nat. Rev. Dis. Primers, 2016, 2, 16061.
[http://dx.doi.org/10.1038/nrdp.2016.61] [PMID: 27558151]
[10]
Klauke, A-L.; Racz, I.; Pradier, B.; Markert, A.; Zimmer, A.M.; Gertsch, J.; Zimmer, A. The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain. Eur. Neuropsychopharmacol., 2014, 24(4), 608-620.
[http://dx.doi.org/10.1016/j.euroneuro.2013.10.008] [PMID: 24210682]
[11]
Singh, G.; Marimuthu, P.; de Heluani, C.S.; Catalan, C.A.N. Antioxidant and biocidal activities of Carum nigrum (seed) essential oil, oleoresin, and their selected components. J. Agric. Food Chem., 2006, 54(1), 174-181.
[http://dx.doi.org/10.1021/jf0518610] [PMID: 16390196]
[12]
Loizzo, M.R.; Tundis, R.; Menichini, F.; Saab, A.M.; Statti, G.A.; Menichini, F. Antiproliferative effects of essential oils and their major constituents in human renal adenocarcinoma and amelanotic melanoma cells. Cell Prolif., 2008, 41(6), 1002-1012.
[http://dx.doi.org/10.1111/j.1365-2184.2008.00561.x] [PMID: 19040575]
[13]
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), 3007-3017.
[http://dx.doi.org/10.1002/cam4.816] [PMID: 27696789]
[14]
Jun, N.J.; Mosaddik, A.; Moon, J.Y.; Jang, K-C.; Lee, D-S.; Ahn, K.S.; Cho, S.K. Cytotoxic activity of β-Caryophyllene oxide isolated from Jeju Guava (Psidium cattleianum sabine). Leaf., 2011, 53, 242-246.
[15]
Dahham, S.S.; Tabana, Y.M.; Iqbal, M.A.; Ahamed, M.B.; Ezzat, M.O.; Majid, A.S.; Majid, A.M. The anticancer, antioxidant and antimicrobial properties of the sesquiterpene β-Caryophyllene from the essential oil of Aquilaria crassna. Molecules, 2015, 20(7), 11808-11829.
[http://dx.doi.org/10.3390/molecules200711808] [PMID: 26132906]
[16]
Pan, Z.; Wang, S-K.; Cheng, X-L.; Tian, X-W.; Wang, J. Caryophyllene oxide exhibits anti-cancer effects in MG-63 human osteosarcoma cells via the inhibition of cell migration, generation of reactive oxygen species and induction of apoptosis. Bangladesh J. Pharmacol., 2016, 11, 817.
[http://dx.doi.org/10.3329/bjp.v11i4.27517]
[17]
Park, K-R.; Nam, D.; Yun, H-M.; Lee, S-G.; Jang, H-J.; Sethi, G.; Cho, S.K.; Ahn, K.S.; Lowe, S.W.; Raymond, E.; Wu, C.T.; Chang, C. β-Caryophyllene oxide inhibits growth and induces apoptosis through the suppression of PI3K/AKT/mTOR/S6K1 pathways and ROS-mediated MAPKs activation. Cancer Lett., 2011, 312(2), 178-188.
[http://dx.doi.org/10.1016/j.canlet.2011.08.001] [PMID: 21924548]
[18]
Cipriano, M.; Neta, S.; Vittorazzi, C.; Guimarães, A.C.; Damasceno, J.; Martins, L.; Fronza, M.; Coutinho Endringer, D.; Scherer, R.; Guimar, A.C.; Damasceno, J. Effects of β-Caryophyllene and Murraya paniculata essential oil in the murine hepatoma cells and in the bacteria and fungi 24-h time-kill curve studies. Pharm. Biol., 2017, 55(1), 190-197.
[19]
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
[http://dx.doi.org/10.1155/2012/872394] [PMID: 22567036]
[20]
Sinibaldi, D.; Wharton, W.; Turkson, J.; Bowman, T.; Pledger, W.J.; Jove, R. Induction of p21WAF1/CIP1 and cyclin D1 expression by the Src oncoprotein in mouse fibroblasts: Role of activated STAT3 signaling. Oncogene, 2000, 19(48), 5419-5427.
[http://dx.doi.org/10.1038/sj.onc.1203947] [PMID: 11114718]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy