Research Article | Volume: 8, Issue: 9, September, 2018

Ethyl acetate fraction of garlic (Allium sativum) inhibits the viability of MCF7 and HepG2 through induction of apoptosis and G2/M phase cell cycle arrest

Amira M. Shaban Ola Hammouda Laila Abou Ghazala Mai Raslan Mohammed A. El-Magd   

Open Access   

Published:  Sep 30, 2018

DOI: 10.7324/JAPS.2018.8920
Abstract

Background: Garlic (Allium sativum) with its main component organosulfur compounds (OSCs) has an anticancer effect against a large verity of cancer cells. This anticancer effect was studied on individual garlic components, rather than fractions. Methods: Herein, we investigated the anticancer effect of different garlic fractions on the MCF7 and HepG2 cells and studied the underlying mechanism. Results: Different garlic fractions, extracted by methylene chloride (MC), petroleum ether (PE), ethyl acetate (EtOAc) and butanol (B) solvents, each alone exhibited significant dose-dependent anti-proliferative activity on MCF7 and HepG2 cells with best results for EtOAc with IC50 values 21.32 and 26.22 μg/ml, respectively, as compared to vehicle-treated cells. HPLC analysis revealed the presence of 14 components in EtOAc fraction with highest concentrations for linoleic acid (LA) and S-allylthiocysteine (SAC). EtOAc fraction inhibited cancer cells proliferation through induction of apoptosis (revealed by a significant increase in mRNA levels of apoptotic markers, Caspase 3 and Bax and a significant decrease in mRNA levels of the anti-apoptotic marker, Bcl2) and cell cycle arrest in G2/M phase (indicated by increase in number of MCF7 and HepG2 cells in this phase). Conclusions: These in vitro results suggest that garlic EtOAc fraction or its main component could be used as an adjuvant to anticancer drug or can help in the development of new anticancer drugs based on components of this fraction.


Keyword:     Allium sativum MTT assay Ethyl acetate fraction Apoptosis Cell cycle arrest HPLC.


Citation:

Shaban AM, Hammouda O, Abou Ghazala L, Raslan M, ElMagd MA. Ethyl acetate fraction of garlic (Allium sativum) inhibits the viability of MCF7 and HepG2 through induction of apoptosis and G2/M phase cell cycle arrest. J App Pharm Sci, 2018; 8(09): 142-150.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Reference

Ariga T, Seki T. Antithrombotic and anticancer effects of garlic-derived sulfur compounds: A review. Biofactors, 2006; 26:93-103.https://doi.org/10.1002/biof.5520260201

Banjerdpongchai R, Wudtiwai B, Khaw-on P, Rachakhom W, Duangnil N, Kongtawelert P. Hesperidin from Citrus. Tumor Biology, 2016; 37:227-237.https://doi.org/10.1007/s13277-015-3774-7

Cerella C, Dicato M, Jacob C, Diederich M. Chemical properties and mechanisms determining the anti-cancer action of garlic-derived organic sulfur compounds. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents), 2011; 11:267-271.https://doi.org/10.2174/187152011795347522

Chajes V, Lavillonniere F, Maillard V, Giraudeau B, Jourdan ML, Sebedio JL, Bougnoux P. Conjugated linoleic acid content in breast adipose tissue of breast cancer patients and the risk of metastasis. Nutr Cancer, 2003; 45:17-23.https://doi.org/10.1207/S15327914NC4501_2

Chan JM, Wang F, Holly EA. Vegetable and fruit intake and pancreatic cancer in a population-based case-control study in the San Francisco bay area. Cancer Epidemiology and Prevention Biomarkers, 2005; 14:2093-2097.https://doi.org/10.1158/1055-9965.EPI-05-0226

Chen Y-C, Kao T-H, Tseng C-Y, Chang W-T, Hsu C-L. Methanolic extract of black garlic ameliorates diet-induced obesity via regulating adipogenesis, adipokine biosynthesis, and lipolysis. Journal of Functional Foods, 2014; 9:98-108.https://doi.org/10.1016/j.jff.2014.02.019

de Mesquita ML, de Paula JE, Pessoa C, de Moraes MO, Costa- Lotufo LV, Grougnet R, Michel S, Tillequin F, Espindola LS. Cytotoxic activity of Brazilian Cerrado plants used in traditional medicine against cancer cell lines. Journal of Ethnopharmacology, 2009; 123:439-445.https://doi.org/10.1016/j.jep.2009.03.018

Deng Y, Sriwiriyajan S, Tedasen A, Hiransai P, Graidist P. Anti-cancer effects of Piper nigrum via inducing multiple molecular signaling in vivo and in vitro. Journal of Ethnopharmacology, 2016; 188:87-95.https://doi.org/10.1016/j.jep.2016.04.047

Desai UN, Shah KP, Mirza SH, Panchal DK, Parikh SK, Rawal RM. Enhancement of the cytotoxic effects of Cytarabine in synergism with Hesperidine and Silibinin in Acute Myeloid Leukemia: An in-vitro approach. Journal of cancer research and therapeutics, 2015; 11:352.https://doi.org/10.4103/0973-1482.157330

Durgam VR, Fernandes G. The growth inhibitory effect of conjugated linoleic acid on MCF-7 cells is related to estrogen response system. Cancer Lett, 1997; 116:121-130.https://doi.org/10.1016/S0304-3835(97)00192-4

El-Magd MA, Khamis A, Nasr Eldeen SK, Ibrahim WM, Salama AF. Trehalose enhances the antitumor potential of methotrexate against mice bearing Ehrlich ascites carcinoma. Biomedicine & Pharmacotherapy, 2017a; 92:870-878.https://doi.org/10.1016/j.biopha.2017.06.005

El-Magd MA, Abdo WS, El-Maddaway M, Nasr NM, Gaber RA, El-Shetry ES, Saleh AA, Alzahrani FAA, Abdelhady DH. High doses of S-methylcysteine cause hypoxia-induced cardiomyocyte apoptosis accompanied by engulfment of mitochondaria by nucleus. Biomedicine & Pharmacotherapy, 2017b; 94:589-597.https://doi.org/10.1016/j.biopha.2017.07.100

El-Magd MA, Khalifa SF, A. Alzahrani FA, Badawy AA, El-Shetry ES, Dawood LM, Alruwaili MM, Alrawaili HA, Risha EF, El- Taweel FM, Marei HE. Incensole acetate prevents beta-amyloid-induced neurotoxicity in human olfactory bulb neural stem cells. Biomedicine & Pharmacotherapy, 2018; 105:813-823.https://doi.org/10.1016/j.biopha.2018.06.014

El Roz A, Bard JM, Huvelin JM, Nazih H. The anti-proliferative and pro-apoptotic effects of the trans9, trans11 conjugated linoleic acid isomer on MCF-7 breast cancer cells are associated with LXR activation. Prostaglandins Leukot Essent Fatty Acids, 2013; 88:265-272.https://doi.org/10.1016/j.plefa.2012.12.006

Farag MA, Ali SE, Hodaya RH, El-Seedi HR, Sultani HN, Laub A, Eissa TF, Abou-Zaid FOF, Wessjohann LA. Phytochemical Profiles and Antimicrobial Activities of Allium cepa Red cv. and A. sativum Subjected to Different Drying Methods: A Comparative MS-Based Metabolomics. Molecules, 2017; 22(5):761-767.https://doi.org/10.3390/molecules22050761

Fleischauer AT, Arab L. Garlic and cancer: a critical review of the epidemiologic literature. The Journal of nutrition, 2001; 131:1032S-1040S.https://doi.org/10.1093/jn/131.3.1032S

Fouché G, Cragg G, Pillay P, Kolesnikova N, Maharaj V, Senabe J. In vitro anticancer screening of South African plants. Journal of Ethnopharmacology, 2008; 119:455-461.https://doi.org/10.1016/j.jep.2008.07.005

González CA, Pera G, Agudo A, Bueno-de-Mesquita HB, Ceroti Huang Y-S, Xie N, Su Q, Su J, Huang C, Liao Q-J. Diallyl disulfide inhibits the proliferation of HT-29 human colon cancer cells by inducing differentially expressed genes. Molecular medicine reports, 2011; 4:553-559.

M, Boeing H, Schulz M, Del Giudice G, Plebani M, Carneiro F. Fruit and vegetable intake and the risk of stomach and oesophagus adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC– EURGAST). International journal of cancer, 2006; 118:2559-2566.https://doi.org/10.1002/ijc.21678

Herman-Antosiewicz A, Powolny AA, Singh SV. Molecular targets of cancer chemoprevention by garlic-derived organosulfides. Acta Pharmacologica Sinica, 2007; 28:1355-1364.https://doi.org/10.1111/j.1745-7254.2007.00682.x

Huot PS, Sarkar B, Ma DW. Conjugated linoleic acid alters caveolae phospholipid fatty acid composition and decreases caveolin-1 expression in MCF-7 breast cancer cells. Nutr Res, 2010; 30:179-185.https://doi.org/10.1016/j.nutres.2010.02.003

Li H, Li H-Q, Wang Y, Xu H-X, Fan W-T, Wang M-L, Sun P-H, Xie X-Y. An intervention study to prevent gastric cancer by micro-selenium and large dose of allitridum. Chinese medical journal, 2004; 117:1155-1160.

Lu G, Zhang G, Zheng X, Zeng Y, Xu Z, Zeng W, Wang K. c9, t11-conjugated linoleic acid induces HCC cell apoptosis and correlation with PPAR-gamma signaling pathway. Am J Transl Res, 2015; 7:2752- 2763.

Ma HB, Huang S, Yin XR, Zhang Y, Di ZL. Apoptotic pathway induced by diallyl trisulfide in pancreatic cancer cells. World J Gastroenterol, 2014; 20:193-203.https://doi.org/10.3748/wjg.v20.i1.193

Malki A, El-Saadani M, Sultan AS. Garlic constituent diallyl trisulfide induced apoptosis in MCF7 human breast cancer cells. Cancer Biol Ther, 2009; 8:2175-2185.https://doi.org/10.4161/cbt.8.22.9882

Omar S, Al-Wabel N. Organosulfur compounds and possible mechanism of garlic in cancer. Saudi Pharmaceutical Journal, 2010; 18:51- 58.https://doi.org/10.1016/j.jsps.2009.12.007

Petrovska BB, Cekovska S. Extracts from the history and medical properties of garlic. Pharmacogn Rev, 2010; 4:106-110.https://doi.org/10.4103/0973-7847.65321

Pietenpol J, Stewart Z. Cell cycle checkpoint signaling: Cell cycle arrest versus apoptosis. Toxicology, 2002; 181:475-481.https://doi.org/10.1016/S0300-483X(02)00460-2

Ross SA, Finley JW, Milner JA. Allyl sulfur compounds from garlic modulate aberrant crypt formation. The Journal of nutrition, 2006; 136:852S-854S.https://doi.org/10.1093/jn/136.3.852S

Saad E, Marei H, El-Magd M, El-Fatiry H. Molecular Characterization of Olfactory Bulb Neural Stem Cells during Proliferation and Differentiation. J App Pharm Sci, 2018; 8:087-092.

Setiawan VW, Yu G-P, Lu Q-Y, Lu M-L, Yu S-Z, Mu L, Zhang J-G, Kurtz RC, Cai L, Hsieh C-C. Allium vegetables and stomach cancer risk in China. Asian Pacific journal of cancer prevention: APJCP, 2005; 6:387.

Shah U, Shah R, Acharya S, Acharya N. Novel anticancer agents from plant sources. Chinese journal of natural medicines, 2013; 11:16-23.https://doi.org/10.1016/S1875-5364(13)60002-3

Song HJ, Sneddon AA, Heys SD, Wahle KW. Regulation of fatty acid synthase (FAS) and apoptosis in estrogen-receptor positive and negative breast cancer cells by conjugated linoleic acids. Prostaglandins Leukot Essent Fatty Acids, 2012; 87:197-203.https://doi.org/10.1016/j.plefa.2012.09.002

Trio PZ, You S, He X, He J, Sakao K, Hou DX. Chemopreventive functions and molecular mechanisms of garlic organosulfur compounds. Food Funct, 2014; 5:833-844.https://doi.org/10.1039/c3fo60479a

Voorrips LE, Brants HA, Kardinaal AF, Hiddink GJ, van den Brandt PA, Goldbohm RA. Intake of conjugated linoleic acid, fat, and other fatty acids in relation to postmenopausal breast cancer: the Netherlands Cohort Study on Diet and Cancer. Am J Clin Nutr, 2002; 76:873-882.https://doi.org/10.1093/ajcn/76.4.873

Wang LS, Huang YW, Liu S, Yan P, Lin YC. Conjugated linoleic acid induces apoptosis through estrogen receptor alpha in human breast tissue. BMC Cancer, 2008; 8:208.https://doi.org/10.1186/1471-2407-8-208

Wu P-P, Chung H-W, Liu K-C, Wu RS-C, Yang J-S, Tang N-Y, Lo C, Hsia T-C, Yu C-C, Chueh F-S. Diallyl sulfide induces cell cycle arrest and apoptosis in HeLa human cervical cancer cells through the p53, caspase-and mitochondria-dependent pathways. International Journal of Oncology, 2011; 38:1605-1613.

Xiao D, Zeng Y, Singh SV. Diallyl trisulfide-induced apoptosis in human cancer cells is linked to checkpoint kinase 1-mediated mitotic arrest. Mol Carcinog, 2009a; 48:1018-1029.https://doi.org/10.1002/mc.20553

Xiao D, Zeng Y, Hahm ER, Kim YA, Ramalingam S, Singh SV. Diallyl trisulfide selectively causes Bax- and Bak-mediated apoptosis in human lung cancer cells. Environ Mol Mutagen, 2009b; 50:201-212.https://doi.org/10.1002/em.20431

Xiao D, Herman-Antosiewicz A, Antosiewicz J, Xiao H, Brisson M, Lazo JS, Singh SV. Diallyl trisulfide-induced G(2)-M phase cell cycle arrest in human prostate cancer cells is caused by reactive oxygen species-dependent destruction and hyperphosphorylation of Cdc 25 C. Oncogene, 2005; 24:6256-6268.https://doi.org/10.1038/sj.onc.1208759

Zheng JS, Hu XJ, Zhao YM, Yang J, Li D. Intake of fish and marine n-3 polyunsaturated fatty acids and risk of breast cancer: meta-analysis of data from 21 independent prospective cohort studies. BMJ, 2013; 346:f3706.https://doi.org/10.1136/bmj.f3706

Zhou W, Simpson PJ, McFadden JM, Townsend CA, Medghalchi SM, Vadlamudi A, Pinn ML, Ronnett GV, Kuhajda FP. Fatty acid synthase inhibition triggers apoptosis during S phase in human cancer cells. Cancer Res, 2003; 63:7330-7337.

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