Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

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

Research Article

Crude Methanol Extract of Rosin Gum Exhibits Specific Cytotoxicity against Human Breast Cancer Cells via Apoptosis Induction

Author(s): Salwa M. El-Hallouty, Ahmed A.F. Soliman, Amr Nassrallah*, Ahmad Salamatullah, Mohammed S. Alkaltham, Khaled Y. Kamal, Eman A. Hanafy, Hanan S. Gaballa and Mourad A.M. Aboul-Soud

Volume 20, Issue 8, 2020

Page: [1028 - 1036] Pages: 9

DOI: 10.2174/1871520620666200423074826

Price: $65

Abstract

Background: Rosin (Colophony) is a natural resin derived from species of the pine family Pinaceae. It has wide industrial applications including printing inks, photocopying paper, adhesives and varnishes, soap and soda. Rosin and its derivatives are employed as ingredients in various pharmaceutical products such as ointments and plasters. Rosin-based products contain allergens that may exert some occupational health problems such as asthma and contact dermatitis.

Objective: Our knowledge of the pharmaceutical and medicinal properties of rosin is limited. The current study aims at investigating the cytotoxic potential of Rosin-Derived Crude Methanolic Extract (RD-CME) and elucidation of its mode-of-action against breast cancer cells (MCF-7 and MDA-MB231).

Methods: Crude methanol extract was prepared from rosin. Its phenolic contents were analyzed by Reversed- Phase High-Performance Liquid Chromatography (RP-HPLC). Antioxidant activity was evaluated by DPPH radical-scavenging assay. Antiproliferation activity against MCF-7 and MDA-MB231 cancerous cells was investigated by MTT assay; its potency compared with doxorubicin as positive control and specificity were assessed compared to two non-cancerous cell lines (BJ-1 and MCF-12F). Selected apoptosis protein markers were assayed by western blotting. Cell cycle analysis was performed by Annexin V-FITC/PI FACS assay.

Results: RD-CME exhibited significant and selective cytotoxicity against the two tested breast cancer cells (MCF-7 and MDA-MB231) compared to normal cells as revealed by MTT assay. ELISA and western blotting indicated that the observed antiproliferative activity of RD-CME is mediated via the engagement of an intrinsic apoptosis signaling pathway, as judged by enhanced expression of key pro-apoptotic protein markers (p53, Bax and Casp 3) relative to vehicle solvent-treated MCF-7 control cells.

Conclusion: To our knowledge, this is the first report to investigate the medicinal anticancer and antioxidant potential of crude methanolic extract derived from colophony rosin. We provided evidence that RD-CME exhibits strong antioxidant and anticancer effects. The observed cytotoxic activity against MCF-7 is proposed to take place via G2/M cell cycle arrest and apoptosis. Colophony resin has a great potential to join the arsenal of plantderived natural anticancer drugs. Further thorough investigation of the potential cytotoxicity of RD-CME against various cancerous cell lines is required to assess the spectrum and potency of its novel activity.

Keywords: Breast cancer, colophony rosin, cell cycle arrest, antiproliferation, apoptosis, methanol extract.

Graphical Abstract
[1]
Report on the Latest Estimates on the Global Burden of Cancer 2018.https://www.iarc.fr/wp-content/uploads/2018/09/pr263_E.pdf
[2]
Ibrahim, A.S.; Khaled, H.M.; Mikhail, N.N.H.; Baraka, H.; Kamel, H. Cancer incidence in egypt: results of the national population-based cancer registry program. J. Cancer Epidemiol., 2014, 2014437971
[http://dx.doi.org/10.1155/2014/437971] [PMID: 25328522]
[3]
Aboul-Soud, M.A.M.; El-Shemy, H.A.; Aboul-Enein, K.M.; Mahmoud, A.M.; Al-Abd, A.M.; Lightfoot, D.A. Effects of plant-derived anti-leukemic drugs on individualized leukemic cell population profiles in Egyptian patients. Oncol. Lett., 2016, 11(1), 642-648.
[http://dx.doi.org/10.3892/ol.2015.3916] [PMID: 26870259]
[4]
Krause, J.; Tobin, G. Discovery, development and regulation of natural products. In Using old solutions to new problems-natural drug discovery in the 21st century. Intech, 2013, p 3-35.
[5]
Çoban, E.A.; Tecimel, D.; Şahin, F.; Deniz, A.A.H. Targeting cancer metabolism and Cell cycle by plant-derived compounds. Adv. Exp. Med. Biol.,, 2019. [Ahead of publication].
[http://dx.doi.org/10.1007/5584_2019_449] [PMID: 31749136]
[6]
El-Shemy, H.A.; Aboul-Soud, M.A.M.; Nassr-Allah, A.A.; Aboul-Enein, K.M.; Kabash, A.; Yagi, A. Antitumor properties and modulation of antioxidant enzymes’ activity by Aloe vera leaf active principles isolated via supercritical carbon dioxide extraction. Curr. Med. Chem., 2010, 17(2), 129-138.
[http://dx.doi.org/10.2174/092986710790112620] [PMID: 19941474]
[7]
Understanding Chemotherapy: A Guide for People with Cancer, Their Families and Friends; Cancer Council Australia: Woolloomooloo, Australia, 2016. ISBN 978 1 925136 18 0.
[8]
Perret, L. [Benedictus Olai: A useful book of medicine, 1578. A quadricentennial. Some aspects of sixteenth-century healing arts]. Nord. Medicinhist. Arsb., 1980(Suppl. 6), 118-121.
[PMID: 11628472]
[9]
Kar, A. Pharmacognosy and Pharmacobiotechnology; New Age International: India, 2003.
[10]
Sadhra, S.; Foulds, I.S.; Gray, C.N.; Koh, D.; Gardiner, K. Colophony--uses, health effects, airborne measurement and analysis. Ann. Occup. Hyg., 1994, 38(4), 385-396.
[PMID: 7978961]
[11]
Kumar, S.; Gupta, S.K. Rosin: a naturally derived excipient in drug delivery systems. Polim. Med., 2013, 43(1), 45-48.
[PMID: 23808195]
[12]
Färm, G. Contact allergy to colophony. Clinical and experimental studies with emphasis on clinical relevance. Acta Derm. Venereol. Suppl. (Stockh.), 1998, 201, 1-42.
[PMID: 9833065]
[13]
Tsuruta, D.; Sowa, J.; Tsuruta, K.; Ishii, M.; Kobayashi, H. Allergic contact dermatitis caused by gum rosin and wood rosin in Tako-no-Suidashi ointment. J. Dermatol., 2011, 38(10), 993-995.
[http://dx.doi.org/10.1111/j.1346-8138.2011.01242.x] [PMID: 21592201]
[14]
Karlberg, A-T.; Gäfvert, E. Isolated colophony allergens as screening substances for contact allergy. Contact Dermat., 1996, 35(4), 201-207.
[http://dx.doi.org/10.1111/j.1600-0536.1996.tb02358.x] [PMID: 8957638]
[15]
Ijeh, I.; Omodamiro, O.; Nwanna, I. Antimicrobial effects of aqueous and ethanolic fractions of two spices, Ocimum gratissimum and Xylopia aethiopica. Afr. J. Biotechnol., 2005, 4(9), 953-956.
[16]
Kedare, S.B.; Singh, R.P. Genesis and development of DPPH method of antioxidant assay. J. Food Sci. Technol., 2011, 48(4), 412-422.
[http://dx.doi.org/10.1007/s13197-011-0251-1] [PMID: 23572765]
[17]
Patel Rajesh, M.; Patel Natvar, J. In vitro antioxidant activity of coumarin compounds by DPPH, Super oxide and nitric oxide free radical scavenging methods. J. Adv. Pharm. Educ. Res., 2011, 1, 52-68.
[18]
Aboul-Soud, M.A.M.; Al-Amri, M.Z.; Kumar, A.; Al-Sheikh, Y.A.; Ashour, A.E.; El-Kersh, T.A. Specific cytotoxic effects of parasporal crystal proteins isolated from native Saudi Arabian Bacillus thuringiensis strains against cervical cancer cells. Molecules, 2019, 24(3), 506.
[http://dx.doi.org/10.3390/molecules24030506] [PMID: 30708936]
[19]
Kirkin, V.; Joos, S.; Zörnig, M. The role of Bcl-2 family members in tumorigenesis. Biochim. Biophys. Acta Mol. Cell Res., 2004, 1644(2-3), 229-249.
[20]
Hirao, A.; Kong, Y.Y.; Matsuoka, S.; Wakeham, A.; Ruland, J.; Yoshida, H.; Liu, D.; Elledge, S.J.; Mak, T.W. DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Science, 2000, 287(5459), 1824-1827.
[http://dx.doi.org/10.1126/science.287.5459.1824] [PMID: 10710310]
[21]
Chen, C-J.; Makino, S. Murine coronavirus replication induces cell cycle arrest in G0/G1 phase. J. Virol., 2004, 78(11), 5658-5669.
[http://dx.doi.org/10.1128/JVI.78.11.5658-5669.2004] [PMID: 15140963]
[22]
Kuribayashi, K.; Mayes, P.A.; El-Deiry, W.S. What are caspases 3 and 7 doing upstream of the mitochondria? Cancer Biol. Ther., 2006, 5(7), 763-765.
[http://dx.doi.org/10.4161/cbt.5.7.3228] [PMID: 16921264]
[23]
Greenwell, M.; Rahman, P.K.S.M. Medicinal plants: Their use in anticancer treatment. Int. J. Pharm. Sci. Res., 2015, 6(10), 4103-4112.
[PMID: 26594645]
[24]
Moon, D.; McCormack, D.; McDonald, D.; McFadden, D. Pterostilbene induces mitochondrially derived apoptosis in breast cancer cells in vitro. J. Surg. Res., 2013, 180(2), 208-215.
[http://dx.doi.org/10.1016/j.jss.2012.04.027] [PMID: 22572619]
[25]
Ozaki, T.; Nakagawara, A. Role of p53 in cell death and human cancers. Cancers (Basel), 2011, 3(1), 994-1013.
[http://dx.doi.org/10.3390/cancers3010994] [PMID: 24212651]
[26]
Patil, J.B.; Kim, J.; Jayaprakasha, G.K. Berberine induces apoptosis in breast cancer cells (MCF-7) through mitochondrial-dependent pathway. Eur. J. Pharmacol., 2010, 645(1-3), 70-78.
[http://dx.doi.org/10.1016/j.ejphar.2010.07.037] [PMID: 20691179]
[27]
Foo, J.B.; Yazan, L.S.; Tor, Y.S.; Armania, N.; Ismail, N.; Imam, M.U.; Yeap, S.K.; Cheah, Y.K.; Abdullah, R.; Ismail, M. Induction of cell cycle arrest and apoptosis in caspase-3 deficient MCF-7 cells by Dillenia suffruticosa root extract via multiple signalling pathways. BMC Complement. Altern. Med., 2014, 14(1), 197.
[http://dx.doi.org/10.1186/1472-6882-14-197] [PMID: 24947113]
[28]
Esmaeili-Mahani, S.; Falahi, F.; Yaghoobi, M.M. Proapoptotic and antiproliferative effects of Thymus caramanicus on human breast cancer cell line (MCF-7) and its interaction with anticancer drug vincristine. Evid.-Based Complem. Altern. Med.: eCAM, 2014, 893247-893247.
[29]
Kamal, K.Y.; Herranz, R.; van Loon, J.J.W.A.; Medina, F.J. Cell cycle acceleration and changes in essential nuclear functions induced by simulated microgravity in a synchronized Arabidopsis cell culture. Plant Cell Environ., 2019, 42(2), 480-494.
[http://dx.doi.org/10.1111/pce.13422] [PMID: 30105864]
[30]
Kamal, K.Y.; Herranz, R.; van Loon, J.J.W.A.; Medina, F.J. Simulated microgravity, Mars gravity, and 2g hypergravity affect cell cycle regulation, ribosome biogenesis, and epigenetics in Arabidopsis cell cultures. Sci. Rep., 2018, 8(1), 6424.
[http://dx.doi.org/10.1038/s41598-018-24942-7] [PMID: 29686401]
[31]
Kamal, K.Y.; van Loon, J.J.W.A.; Medina, F.J.; Herranz, R. Differential transcriptional profile through cell cycle progression in Arabidopsis cultures under simulated microgravity. Genomics, 2019, 111(6), 1956-1965.
[http://dx.doi.org/10.1016/j.ygeno.2019.01.007] [PMID: 30641127]
[32]
Herranz, R. Mechanisms of disruption of meristematic competence by microgravity in Arabidopsis seedlings. Plant Signal. Behav., 2014, 9 e28289
[http://dx.doi.org/10.4161/psb.28289]
[33]
Hamouchene, H.; Arlt, V.M.; Giddings, I.; Phillips, D.H. Influence of cell cycle on responses of MCF-7 cells to benzo[a]pyrene. BMC Genomics, 2011, 12(1), 333.
[http://dx.doi.org/10.1186/1471-2164-12-333] [PMID: 21714911]

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