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Current Cancer Therapy Reviews

Editor-in-Chief

ISSN (Print): 1573-3947
ISSN (Online): 1875-6301

Research Article

Flavonoid Content in Extract Fractions of Morus alba (mulberry) Inducing Apoptosis in A549 Human Epithelial Lung Carcinoma Cells

Author(s): Om Prakash*, Ruchi Singh, Rajesh Kumar, Namrata Singh, Neelam Verma, Amresh Gupta and Akash Ved

Volume 18, Issue 2, 2022

Published on: 06 July, 2022

Page: [152 - 161] Pages: 10

DOI: 10.2174/1573394718666220401094203

Price: $65

Abstract

Background: Cancer is one of the leading chronic diseases with a high mortality rate worldwide. Current statistical studies on cancer from the World Health Organization (WHO) in 2020 estimated that cancer is the first or second leading cause of death.

Objective: The current study investigated the phytochemical, antioxidant, and anticancer effect of MeOH extract of Morus alba leaves, superoxide scavenging assay, metal chelating, DPPH, and MTT assay employed.

Methods: MTT assay was performed on A549 cells and chick embryo fibroblasts were used as the control. DNA fragmentation and real-time assays were performed to check apoptosis and gene expression levels.

Results: Findings suggest that the MeOH extract of Morus alba exhibited a significant antioxidant activity compared to standard antioxidants. MeOH extract and chloroform fraction exhibited strong selectivity of toxicity toward A549 human lung carcinoma cells without affecting normal cells. The chloroform fraction was found to be most active in the MTT assay against A549 cells, while it was less toxic to normal cells. Cells exposed to IC50 concentration for the cytotoxicity study of the chloroform fraction exhibited a breakdown of DNA. Increased expression of p53, Bax, caspase-3 and reduced expression of Bcl-2 gene gave evidence that the chloroform fraction might induce apoptosis.

Conclusion: It was concluded that the MeOH extract and its fractions of Morus alba leaves possessed immense potential for tumor treatment. Therefore, it would be necessary to carry out further studies to isolate and identify the active principles responsible for these activities.

Keywords: Anticancer activity, MTT assay, apoptosis, A-549, Morus alba, DNA fragmentation.

Graphical Abstract

[1]
Prakash O, Usmani S, Singh R, Mahapatra D, Gupta A. Cancer chemotherapy by novel bio-active natural products, looking towards the future. Curr Cancer Ther Rev 2019; 15(1): 37-49.
[http://dx.doi.org/10.2174/1573394714666180321151315]
[2]
Prakash O, Kumar A, Kumar P, Ajeet A. Anticancer potential of plants and natural products, A review. Am J Pharmacol Sci 2013; 1(6): 104-15.
[http://dx.doi.org/10.12691/ajps-1-6-1]
[3]
Prakash O, Usmani S, Gupta A, Singh R, Singh N, Ved A. Bioactive polyphenols as promising natural medicinal agents against cancer, The emerging trends and prospective goals. Curr Bioact Compd 2020; 16(3): 243-64.
[http://dx.doi.org/10.2174/1573407214666181030122046]
[4]
Pistritto G, Trisciuoglio D, Ceci C, Garufi A, D’Orazi G. Apoptosis as anticancer mechanism: Function and dysfunction of its modulators and targeted therapeutic strategies. Aging (Albany NY) 2016; 8(4): 603-19.
[http://dx.doi.org/10.18632/aging.100934] [PMID: 27019364]
[5]
Jordan MA, Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer 2004; 4(4): 253-65.
[http://dx.doi.org/10.1038/nrc1317] [PMID: 15057285]
[6]
Kawabe T. G2 checkpoint abrogators as anticancer drugs. Mol Cancer Ther 2004; 3(4): 513-9.
[PMID: 15078995]
[7]
Millimouno FM, Dong J, Yang L, Li J, Li X. Targeting apoptosis pathways in cancer and perspectives with natural compounds from moth-er nature. Cancer Prev Res (Phila) 2014; 7(11): 1081-107.
[http://dx.doi.org/10.1158/1940-6207.CAPR-14-0136] [PMID: 25161295]
[8]
Ning Z, Lu C, Zhang Y, et al. Application of plant metabonomics in quality assessment for large-scale production of traditional Chinese medicine. Planta Med 2013; 79(11): 897-908.
[http://dx.doi.org/10.1055/s-0032-1328656] [PMID: 23807813]
[9]
Gao H, Lamusta J, Zhang WF, et al. Tumor cell selective cytotoxicity and apoptosis induction by an herbal preparation from Brucea ja-vanica. N Am J Med Sci (Boston) 2011; 4(2): 62-6.
[http://dx.doi.org/10.7156/v4i2p062] [PMID: 21654932]
[10]
Valiyari S, Baradaran B, Delazar A, Pasdaran A, Zare F. Dichloromethane and methanol extracts of Scrophularia oxysepala induces apop-tosis in MCF-7 human breast cancer cells. Adv Pharm Bull 2012; 2(2): 223-31.
[http://dx.doi.org/10.5681/apb.2012.034] [PMID: 24312797]
[11]
Singh S, Sharma B, Kanwar SS, Kumar A. Lead phytochemicals for anticancer drug development. Front Plant Sci 2016; 7: 1667.
[http://dx.doi.org/10.3389/fpls.2016.01667] [PMID: 27877185]
[12]
Badgujar N, Mistry KN, Chudasama P, Patel JS. In-vitro antioxidant and cytotoxic effects of methanol extracts of vitex negundo.; lantana camara.; bauhinia variegata and bauhinia racemosa on human cancer cell lines. Indian J Pharm Sci 2017; 79(3): 431-7.
[http://dx.doi.org/10.4172/pharmaceutical-sciences.1000246]
[13]
Zahri S, Razavi SM, Niri FH, Mohammadi S. Induction of programmed cell death by Prangos uloptera, a medicinal plant. Biol Res 2009; 42(4): 517-22.
[http://dx.doi.org/10.4067/S0716-97602009000400013] [PMID: 20140307]
[14]
Yousefzadi M, Heidari M, Akbarpour M, Mirjalili MH, Zeinali A, Parsa M. In vitro cytotoxic activity of the essential oil of Dorema am-moniacum D. Don. Middle East J Sci Res 2011; 7: 511-4.
[http://dx.doi.org/10.1371/journal.pone.0110003]
[15]
Chan EW, Lye PY, Wong SK. Phytochemistry, pharmacology, and clinical trials of Morus alba. Chin J Nat Med 2016; 14(1): 17-30.
[http://dx.doi.org/10.3724/sp.j.1009.2016.00017] [PMID: 26850343]
[16]
Yuan Q, Zhao L. The mulberry (Morus alba L.) fruit-A review of characteristic components and health benefits. J Agric Food Chem 2017; 65(48): 10383-94.
[http://dx.doi.org/10.1021/acs.jafc.7b03614]
[17]
Soonthornsit N, Pitaksutheepong C, Hemstapat W, Utaisincharoen P, Pitaksuteepong T. In vitro anti-inflammatory activity of morus alba l. stem extract in lps-stimulated RAW 264.7 cells. Evid Based Complement Alternat Med 2017; 2017: 3928956.
[http://dx.doi.org/10.1155/2017/3928956] [PMID: 28684966]
[18]
Mandal S, Patra A, Samanta A, et al. Analysis of phytochemical profile of Terminalia arjuna bark extract with antioxidative and antimi-crobial properties. Asian Pac J Trop Biomed 2013; 3(12): 960-6.
[http://dx.doi.org/10.1016/S2221-1691(13)60186-0] [PMID: 24093787]
[19]
Chan EWC, Wong SK, Tangah J, Inoue T, Chan HT. Phenolic constituents and anticancer properties of Morus alba (white mulberry) leaves. J Integr Med 2020; 18(3): 189-95.
[http://dx.doi.org/10.1016/j.joim.2020.02.006] [PMID: 32115383]
[20]
Ha MT, Seong SH, Nguyen TD, et al. Chalcone derivatives from the root bark of Morus alba L. act as inhibitors of PTP1B and α-glucosidase. Phytochemistry 2018; 155: 114-25.
[http://dx.doi.org/10.1016/j.phytochem.2018.08.001] [PMID: 30103164]
[21]
Yu JS, Lim SH, Lee SR, Choi CI, Kim KH. Antioxidant and anti-inflammatory effects of white mulberry (Morus alba L.) fruits on lipopol-ysaccharide-stimulated RAW 264.7 macrophages. Molecules 2021; 26(4): 920.
[http://dx.doi.org/10.3390/molecules26040920] [PMID: 33572374]
[22]
Nile SH, Nile AS, Keum YS. Total phenolics.; antioxidant.; antitumor.; and enzyme inhibitory activity of Indian medicinal and aromatic plants extracted with different extraction methods. 3 Biotech 2017; 7(1): 76.
[http://dx.doi.org/10.1007/s13205-017-0706-9]
[23]
Yu M, Gouvinhas I, Rocha J, Barros AIRNA. Phytochemical and antioxidant analysis of medicinal and food plants towards bioactive food and pharmaceutical resources. Sci Rep 2021; 11(1): 10041.
[http://dx.doi.org/10.1038/s41598-021-89437-4] [PMID: 33976317]
[24]
Belli S, Rossi M, Molasky N, et al. Effective and novel application of hydrodynamic voltammetry to the study of superoxide radical scav-enging by natural phenolic antioxidants. Antioxidants 2019; 8(1): 14.
[http://dx.doi.org/10.3390/antiox8010014] [PMID: 30621138]
[25]
Martinez CA, Loureiro ME, Oliva MA, Maestri M. Differential responses of superoxide dismutase in freezing resistant Solanum curtilobum and freezing sensitive Solanum tuberosum subjected to oxidative and water stress. Plant Sci 2001; 160(3): 505-15.
[http://dx.doi.org/10.1016/S0168-9452(00)00418-0] [PMID: 11166438]
[26]
Chan E, Lim Y, Omar M. Antioxidant and antibacterial activity of leaves of Etlingera species (Zingiberaceae) in Peninsular Malaysia. Food Chem 2007; 104(4): 1586-93.
[http://dx.doi.org/10.1016/j.foodchem.2007.03.023]
[27]
Anggraini T, Wilma S, Syukri D, Azima F. Total phenolic, anthocyanin, catechins, dpph radical scavenging activity, and toxicity of le-pisanthes alata (blume) leenh. Int J Food Sci 2019; 2019: 9703176.
[http://dx.doi.org/10.1155/2019/9703176] [PMID: 31275958]
[28]
Sylvester PW. Optimization of the tetrazolium dye (MTT) colorimetric assay for cellular growth and viability. Methods Mol Biol 2011; 716: 157-68.
[http://dx.doi.org/10.1007/978-1-61779-012-6_9] [PMID: 21318905]
[29]
Samarakoon SR, Ediriweera MK, Nwokwu CDU, et al. A study on cytotoxic and apoptotic potential of a triterpenoid saponin (3-O-α-L-arabinosyl oleanolic acid) isolated from schumacheria castaneifolia vahl in human non-small-cell lung cancer (NCI-H292) cells. BioMed Res Int 2017; 2017: 9854083.
[http://dx.doi.org/10.1155/2017/9854083] [PMID: 29259993]
[30]
Bong I, Lim P, Balraj P, Sim Ui Hang E, Zakaria Z. Quantitative analysis of the expression of p53 gene in colorectal carcinoma by using real-time PCR. Trop Biomed 2006; 23(1): 53-9.
[PMID: 17041552]
[31]
Min TR, Park HJ, Park MN, Kim B, Park SH. The root bark of Morus alba L. suppressed the migration of human non-small-cell lung can-cer cells through inhibition of epithelial−mesenchymal transition mediated by STAT3 and Src. Int J Mol Sci 2019; 20(9): 2244.
[http://dx.doi.org/10.3390/ijms20092244] [PMID: 31067694]
[32]
Paudel P, Seong SH, Wagle A, Min BS, Jung HA, Choi JS. Antioxidant and anti-browning property of 2-arylbenzofuran derivatives from Morus alba Linn root bark. Food Chem 2020; 309: 125739.
[http://dx.doi.org/10.1016/j.foodchem.2019.125739] [PMID: 31787394]
[33]
Cao YG, Zheng XK, Yang FF, et al. Two new phenolic constituents from the root bark of Morus alba L. and their cardioprotective activity. Nat Prod Res 2018; 32(4): 391-8.
[http://dx.doi.org/10.1080/14786419.2017.1309535] [PMID: 28349742]
[34]
Jiao Y, Wang X, Jiang X, Kong F, Wang S, Yan C. Antidiabetic effects of Morus alba fruit polysaccharides on high-fat diet- and strepto-zotocin-induced type 2 diabetes in rats. J Ethnopharmacol 2017; 199: 119-27.
[http://dx.doi.org/10.1016/j.jep.2017.02.003] [PMID: 28163112]
[35]
Wu YX, Kim YJ, Kwon TH, Tan CP, Son KH, Kim T. Anti-inflammatory effects of mulberry (Morus alba L.) root bark and its active compounds. Nat Prod Res 2020; 34(12): 1786-90.
[http://dx.doi.org/10.1080/14786419.2018.1527832] [PMID: 30470128]
[36]
Jung JW, Ko WM, Park JH, et al. Isoprenylated flavonoids from the root bark of Morus alba and their hepatoprotective and neuroprotec-tive activities. Arch Pharm Res 2015; 38(11): 2066-75.
[http://dx.doi.org/10.1007/s12272-015-0613-8] [PMID: 25981820]
[37]
Tacar O, Sriamornsak P, Dass CR. Doxorubicin: An update on anticancer molecular action, toxicity and novel drug delivery systems. J Pharm Pharmacol 2013; 65(2): 157-70.
[http://dx.doi.org/10.1111/j.2042-7158.2012.01567.x] [PMID: 23278683]
[38]
Kepp O, Galluzzi L, Lipinski M, Yuan J, Kroemer G. Cell death assays for drug discovery. Nat Rev Drug Discov 2011; 10(3): 221-37.
[http://dx.doi.org/10.1038/nrd3373] [PMID: 21358741]
[39]
Skommer J, Darzynkiewicz Z, Wlodkowic D. Cell death goes LIVE: Technological advances in real-time tracking of cell death. Cell Cycle 2010; 9(12): 2330-41.
[http://dx.doi.org/10.4161/cc.9.12.11911] [PMID: 20519963]
[40]
Marzo I, Naval J. Bcl-2 family members as molecular targets in cancer therapy. Biochem Pharmacol 2008; 76(8): 939-46.
[http://dx.doi.org/10.1016/j.bcp.2008.06.009] [PMID: 18638457]
[41]
Chang HK, Shin MS, Yang HY, et al. Amygdalin induces apoptosis through regulation of Bax and Bcl-2 expressions in human DU145 and LNCaP prostate cancer cells. Biol Pharm Bull 2006; 29(8): 1597-602.
[http://dx.doi.org/10.1248/bpb.29.1597] [PMID: 16880611]
[42]
Green DR, Kroemer G. The pathophysiology of mitochondrial cell death. Science 2004; 305(5684): 626-9.
[http://dx.doi.org/10.1126/science.1099320] [PMID: 15286356]
[43]
Oren M. Decision making by p53: Life, death and cancer. Cell Death Differ 2003; 10(4): 431-42.
[http://dx.doi.org/10.1038/sj.cdd.4401183] [PMID: 12719720]
[44]
Fulda S, Debatin KM. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 2006; 25(34): 4798-811.
[http://dx.doi.org/10.1038/sj.onc.1209608] [PMID: 16892092]
[45]
Mitupatum T, Aree K, Kittisenachai S, et al. mRNA expression of bax, Bcl-2, p53, Cathepsin B, Caspase-3 and Caspase-9 in the HepG2 cell line following induction by a novel monoclonal Ab Hep88 mAb: Cross-talk for paraptosis and apoptosis. Asian Pac J Cancer Prev 2016; 17(2): 703-12.
[http://dx.doi.org/10.7314/APJCP.2016.17.2.703] [PMID: 26925667]

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