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Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

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

General Research Article

Prunus Armeniaca L. Seed Extract and Its Amygdalin Containing Fraction Induced Mitochondrial-Mediated Apoptosis and Autophagy in Liver Carcinogenesis

Author(s): Samar Hosny, Heba Sahyon, Magdy Youssef and Amr Negm*

Volume 21, Issue 5, 2021

Published on: 08 June, 2020

Page: [621 - 629] Pages: 9

DOI: 10.2174/1871520620666200608124003

Price: $65

Abstract

Background: Despite significant advances in therapeutic interventions, liver cancer is the leading cause of cancer mortality in the world. Potential phytochemicals have shown to be promising agents against many life-threatening diseases because of their low toxicity and potential effectiveness.

Objective: The current study aims to conduct an in vitro investigation of the anticancer activity of Apricot Extract (AE) and Amygdalin Containing Fraction (ACF), additionally studying their therapeutic effects on DMBAinduced liver carcinogenesis mice model to highlight their related biochemical and molecular mechanisms.

Methods and Results: Amygdalin was isolated from the seeds of P. armeniaca L. Male mice received AE or ACF, DMBA, DMBA+AE, DMBA+ACF, and vehicles. The oxidative stress and antioxidant markers, cell proliferation by flow cytometric analysis of Proliferating Cell Nuclear Antigen (PCNA) expression, angiogenesis marker (VEGF), inflammatory marker (TNF-α), apoptotic, anti-apoptotic and autophagy genes expression (caspase-3, Bcl-2, and Beclin-1) were investigated. AE and ACF were found to stimulate the apoptotic process by up-regulating caspase-3 expression and down-regulating Bcl-2 expression. They also reduced VEGF and PCNA levels and increased the antioxidant defense system. Moreover, AE and ACF treatments also inhibited HepG2 and EAC cell proliferation and up-regulated Beclin-1 expression.

Conclusion: This study provides evidence that, in DMBA-induced hepatocarcinogenesis, the key proteins involved in the proliferation, angiogenesis, autophagy, and apoptosis are feasible molecular targets for hepatotherapeutic potential using AE and ACF.

Keywords: Amygdalin, Bcl-2, Beclin-1, caspase-3, hepatocarcinogenesis, autophagy.

Graphical Abstract
[1]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; 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.
[http://dx.doi.org/10.3322/caac.21492]
[2]
El-Shaheed, S.; Sahyon, H.; Youssef, M.; Negm, A. Protocatechuic acid decreased telomerase reverse transcriptase (Tert) expression in dmba-induced liver carcinogenesis mice model. Ann. Cancer Res. Ther., 2020, 28(1), 25-31.
[http://dx.doi.org/10.4993/acrt.28.25]
[3]
Hosny, S.; Sahyon, H.; Youssef, M.; Negm, A. Oleanolic acid suppressed DMBA-induced liver carcinogenesis through induction of mitochondrial-mediated apoptosis and autophagy. Nutr. Cancer, 2020, 1-15.
[http://dx.doi.org/10.1080/01635581.2020.1776887]
[4]
Khan, H.; Saeedi, M.; Nabavi, S.M.; Mubarak, M.S.; Bishayee, A. Glycosides from medicinal plants as potential anticancer agents: Emerging trends towards future drugs. Curr. Med. Chem., 2018, 26(13), 2389-2406.
[http://dx.doi.org/10.2174/0929867325666180403145137]
[5]
Erdogan-Orhan, I.; Kartal, M. Insights into research on phytochemistry and biological activities of Prunus armeniaca L. (Apricot). Food Res. Int., 2011, 44(5), 1238-1243.
[http://dx.doi.org/10.1016/j.foodres.2010.11.014]
[6]
Roussos, P.A.; Denaxa, N.K.; Tsafouros, A.; Efstathios, N.; Intidhar, B. Apricot (Prunus armeniaca L.). InNutritional Composition of Fruit Cultivars; Academic Press: USA, 2015, pp. 19-48.
[http://dx.doi.org/10.1016/B978-0-12-408117-8.00002-7]
[7]
Saleem, M.; Asif, J.; Asif, M.; Saleem, U. Amygdalin, from Apricot kernels, induces apoptosis and causes cell cycle arrest in cancer cells : An updated review. Anticancer. Agents Med. Chem., 2018, 18(12), 1650-1655.
[http://dx.doi.org/10.2174/1871520618666180105161136]
[8]
Bolarinwa, I.F.; Orfila, C.; Morgan, M.R.A. Amygdalin content of seeds, kernels and food products commercially available in the UK. Food Chem., 2014, 152, 133-139.
[http://dx.doi.org/10.1016/j.foodchem.2013.11.002]
[9]
Hashim, Y.Z-Y.; Phirdaous, A.; Azura, A. Screening of anticancer activity from agarwood essential oil. Pharmacognosy Res., 2014, 6(3), 191.
[http://dx.doi.org/10.4103/0974-8490.132593]
[10]
Machana, S.; Weerapreeyakul, N.; Barusrux, S.; Nonpunya, A.; Sripanidkulchai, B.; Thitimetharoch, T. Cytotoxic and apoptotic effects of six herbal plants against the human hepatocarcinoma (HepG2) cell line. Chin. Med., 2011, 6, Article No. 39.
[http://dx.doi.org/10.1186/1749-8546-6-39]
[11]
Mansour, A.; Daba, A.; Baddour, N.; El-Saadani, M.; Aleem, E. Schizophyllan inhibits the development of mammary and hepatic carcinomas induced by 7,12 dimethylbenz(α)anthracene and decreases cell proliferation: Comparison with tamoxifen. J. Cancer Res. Clin. Oncol., 2012, 138(9), 1579-1596.
[http://dx.doi.org/doi.org/10.1007/s00432-012-1224-0]
[13]
Minaiyan, M.; Ghannadi, A.; Asadi, M.; Etemad, M.; Mahzouni, P. Anti-inflammatory effect of Prunus armeniaca L. (Apricot) extracts ameliorates TNBS-induced ulcerative colitis in rats. Res. Pharm. Sci., 2014, 9(4), 225-231.
[14]
Karabulut, A.B.; Önal, Y.; Gül, M. Physiology & pathology mediterranean diet : Bitter apricot kernel and amygdalin treatment effects on a battery of oxidative stress. J. Plant Physiol. Pathol., 2014, 2(3), 2-7.
[15]
Beutler, E.; Duron, O.; Kelly, B.M. Improved method for the determination of blood glutathione. J. Lab. Clin. Med., 1963, 61, 882-888.
[http://dx.doi.org/doi.org/10.1021/acs.biomac.6b00278]
[16]
Draper, H.H.; Hadley, M. Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol., 1990, 186(C), 421-431.
[http://dx.doi.org/doi.org/10.1016/0076-6879(90)86135-I]
[17]
Landberg, G.; Roos, G. Antibodies to proliferating cell nuclear antigen as S-Phase probes in flow cytometric cell cycle analysis. Cancer Res., 1991, 51(17), 4570-4574.
[18]
Livak, K.J.; Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods, 2001, 25(4), 402-408.
[http://dx.doi.org/doi.org/10.1006/meth.2001.1262]
[19]
Nandakumar, N.; Haribabu, L.; Perumal, S.; Balasubramanian, M.P. Therapeutic effect of hesperidin with reference to biotransformation, lysosomal and mitochondrial TCA cycle enzymes against 7,12-dimethylbenz(a) anthracene-induced experimental mammary cellular carcinoma. Biomed. Aging Pathol., 2011, 1(3), 158-168.
[http://dx.doi.org/doi.org/10.1016/j.biomag.2011.09.001]
[20]
Juan, C. Amaya-Salcedo, O. E. C.-G. and J. A. G.-C. Solid-to-Liquid Extraction and HPLC/UV Determination of amygdalin of seeds of apple (Malus pumila Mill): Comparison between traditional-solvent and microwave methodologies. Acta Agron., 2018, 67, 381-388.
[21]
Turczan, J.W.; Medwick, T. Qualitative and quantitative analysis of amygdalin using NMR spectroscopy. Anal. Lett., 1977, 10, 37-41.
[http://dx.doi.org/doi.org/10.1080/00032717708059224]
[22]
Khammas, S.S.; Abbas, S.M.; Khammas, Z.A-A. Extraction and determination of amygdaline in Iraqi plant seeds using the combined simple extraction procedure and high-performance liquid chromatography. Baghdad Sci. J., 2013, 10(2), 350-361.
[23]
Savic, I.M.; Nikolic, V.D.; Savic-Gajic, I.M.; Nikolic, L.B. Optimization of technological procedure for amygdalin isolation from plum seeds (Pruni domesticae Semen). Front. Plant Sci., 2015, 6, 276.
[http://dx.doi.org/doi.org/10.3389/fpls.2015.00276]
[24]
Chang, J.; Zhang, Y. Catalytic degradation of amygdalin by extracellular enzymes from Aspergillus niger. Process Biochem., 2012, 47(2), 195-200.
[http://dx.doi.org/doi.org/10.1016/j.procbio.2011.10.030]
[25]
Abboud, M.M.; Al Awaida, W.; Alkhateeb, H.H.; Abu-Ayyad, A.N. Antitumor action of amygdalin on human breast cancer cells by selective sensitization to oxidative stress. Nutr. Cancer, 2019, 71(3), 1-8.
[http://dx.doi.org/doi.org/10.1080/01635581.2018.1508731]
[26]
Gomaa, E.Z. In vitro antioxidant, antimicrobial, and antitumor activities of bitter almond and sweet apricot (Prunus armeniaca L.) kernels. Food Sci. Biotechnol., 2013, 22(2), 455-463.
[http://dx.doi.org/doi.org/10.1007/s10068-013-0101-1]
[27]
Fernández-Iglesias, A.; Hide, D.; Gracia-Sancho, J. Oxidative Stress in Liver Diseases.Gastrointestinal Tissue: Oxidative Stress and Dietary Antioxidants; Elsevier: Amsterdam, 2017, pp. 125-140.
[http://dx.doi.org/doi.org/10.1016/B978-0-12-805377-5.00009-6]
[28]
Traverso, N.; Ricciarelli, R.; Nitti, M.; Marengo, B.; Furfaro, A.L.; Pronzato, M.A.; Marinari, U.M.; Domenicotti, C. Role of glutathione in cancer progression and chemoresistance. Oxid. Med. Cellular. Longev., 2013, 2013Article ID 972913
[http://dx.doi.org/10.1155/2013/972913]
[29]
Jasna, M.Č.; Vuli, J.J.; Gordana, S.Ć.; Djilas, S.M. Bioactive compounds and antioxidant properties of dried apricot. Acta Period. Technol., 2013, 321, 193-205.
[http://dx.doi.org/doi.org/10.2298/APT1344193C]
[30]
Halenár, M.; Medveďová, M.; Maruniaková, N.; Kolesárová, A. Amygdalin and its effects on animal cells. J. Microbiol. Biotechnol. Food Sci., 2013, 2(1), 2217-2226.
[31]
Makarević, J.; Tsaur, I.; Juengel, E.; Borgmann, H.; Nelson, K.; Thomas, C.; Bartsch, G.; Haferkamp, A.; Blaheta, R.A. Amygdalin delays cell cycle progression and blocks growth of prostate cancer cells in vitro. Life Sci., 2016, 147, 137-142.
[http://dx.doi.org/doi.org/10.1016/j.lfs.2016.01.039]
[32]
Sharma, S.; Satpathy, G.; Gupta, R.K. Nutritional, phytochemical, antioxidant and antimicrobial activity of Prunus armenicus. J. Pharmacogn. Phytochem., 2014, 3(3), 23-28.
[33]
Reuter, S.; Gupta, S.C.; Chaturvedi, M.M.; Aggarwal, B.B. Oxidative stress, inflammation, and cancer: How are they linked? Free Radic. Biol. Med., 2010, 49(11), 1603-1616.
[http://dx.doi.org/doi.org/10.1016/j.freeradbiomed.2010.09.006]
[34]
Meei, L.S.; Kuo, F.C.; Yen, J.S.; Wan, W.L.; Shoei, Y.L.S.; Shing, H.L. Activation of phosphoinositide 3-kinase in response to inflammation and nitric oxide leads to the up-regulation of cyclooxygenase-2 expression and subsequent cell proliferation in mesangial cells. Cell. Signal., 2005, 17(8), 975-984.
[http://dx.doi.org/doi.org/10.1016/j.cellsig.2004.11.015]
[35]
Karabulut, A.B.; Karadag, N.; Gurocak, S.; Kiran, T.; Tuzcu, M.; Sahin, K. Apricot attenuates oxidative stress and modulates of Bax, Bcl-2, caspases, NFκ-B, AP-1, CREB expression of rats bearing DMBA-induced liver damage and treated with a combination of radiotherapy. Food Chem. Toxicol., 2014, 70, 128-133.
[http://dx.doi.org/doi.org/10.1016/j.fct.2014.04.036]
[36]
Hwang, H.J.; Kim, P.; Kim, C.J.; Lee, H.J.; Shim, I.; Yin, C.S.; Yang, Y.; Hahm, D.H. Antinociceptive effect of amygdalin isolated from Prunus armeniaca on formalin-induced pain in rats. Biol. Pharm. Bull., 2008, 31(8), 1559-1564.
[http://dx.doi.org/doi.org/10.1248/bpb.31.1559]
[37]
Belloni, D.; Scabini, S.; Foglieni, C.; Veschini, L.; Giazzon, A.; Colombo, B.; Fulgenzi, A.; Helle, K.B.; Ferrero, M.E.; Corti, A. The Vasostatin-I fragment of chromogranin A inhibits VEGF-induced endothelial cell proliferation and migration. FASEB J., 2007, 21(12), 3052-3062.
[http://dx.doi.org/doi.org/10.1096/fj.06-6829com]
[38]
Wang, Y-L.; Song, T.; Hu, Y-N.; Lu, X-L.; Zhang, Y-X.; Liu, E-Q.; He, S-X. Effects of saikosaponins-D on Ang-2 and VEGF expressions in experimental hepatocarcinoma in rats. J. Xi’an Jiaotong Univ. Med. Sci., 2013, 34(5)
[http://dx.doi.org/doi.org/10.7652/jdyxb201305024]
[39]
Ali, M.M.; Borai, H.I.; Ghanem, H.M.; Abdel-Halim, A.H.; Mousa, F.M. The prophylactic and therapeutic effects of momordica charantia methanol extract through controlling different hallmarks of the hepatocarcinogenesis. Biomed. Pharmacother., 2018, 98, 491-498.
[http://dx.doi.org/10.1016/j.biopha.2017.12.096]
[40]
Ali, A.D.; Ismail, M.F.; Badr, H.A. Hepatoprotective effect of ginger extract against the toxicity of 7,12- Dimethylbenz(a)Anthracene (DMBA) in albino rats. World J. Pharm. Sci., 2013, 1(3).
[41]
Tolomeo, M.; Simoni, D. Drug resistance and apoptosis in Cancer treatment: Development of new apoptosis-inducing agents active in drug resistant malignancies. Curr. Med. Chem. AntiCancer Agents, 2002, 2(3), 387-401.
[42]
Juengel, E.; Afschar, M.; Makarevi, J.; Rutz, J.; Tsaur, I.; Mani, J.; Nelson, K.; Haferkamp, A.; Blaheta, R.A. Amygdalin blocks the in vitro adhesion and invasion of renal cell carcinoma cells by an integrin-dependent mechanism. Int. J. Mol. Med., 2016, 37(3), 843-850.
[http://dx.doi.org/10.3892/ijmm.2016.2454]
[43]
Berardi, D.E.; Campodónico, P.B.; Díaz Bessone, M.I.; Urtreger, A.J.; Todaro, L.B. Autophagy: Friend or foe in breast cancer development, progression, and treatment. Int. J. Breast Cancer, 2011, 2011, 1-7.
[http://dx.doi.org/10.4061/2011/595092]
[44]
Mori, S.; Sawada, T.; Okada, T.; Ohsawa, T.; Adachi, M.; Keiichi, K. New anti-proliferative agent, MK615, from Japanese apricot “Prunus Mume” induces striking autophagy in colon cancer cells in vitro. World J. Gastroenterol., 2007, 13(48), 6512-6517.
[http://dx.doi.org/10.3748/wjg.13.6512]
[45]
Wang, Q.; Guo, W.; Hao, B.; Shi, X.; Lu, Y.; Wong, C.W.M.; Ma, V.W.S.; Yip, T.T.C.; Au, J.S.K.; Hao, Q. Mechanistic study of TRPM2-Ca2+-CAMK2-BECN1 signaling in oxidative stress-induced autophagy inhibition. Autophagy, 2016, 12(8), 1340-1354.
[http://dx.doi.org/10.1080/15548627.2016.1187365]
[46]
Marquez, R.T.; Xu, L. Bcl-2: Beclin 1 Complex: Multiple, mechanisms regulating autophagy/apoptosis toggle switch. Am. J. Cancer Res., 2012, 2(2), 214-221.
[47]
Pattingre, S.; Tassa, A.; Qu, X.; Garuti, R.; Xiao, H.L.; Mizushima, N.; Packer, M.; Schneider, M.D.; Levine, B. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell, 2005, 122(6), 927-939.
[http://dx.doi.org/10.1016/j.cell.2005.07.002]

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