期刊论文详细信息
BMC Complementary and Alternative Medicine
Piper betle shows antioxidant activities, inhibits MCF-7 cell proliferation and increases activities of catalase and superoxide dismutase
Azlina Abdul-Aziz1  M S Kanthimathi1  Noor Nazirahanie Abrahim1 
[1] University of Malaya Centre for Proteomics Research, University of Malaya, 50603 Kuala Lumpur, Malaysia
关键词: HPLC;    Superoxide dismutase;    Catalase;    Cytotoxicity;    MCF-7;    Phenolic;    Antioxidant;    Piper betle;   
Others  :  1231500
DOI  :  10.1186/1472-6882-12-220
 received in 2012-08-14, accepted in 2012-11-07,  发布年份 2012
PDF
【 摘 要 】

Background

Breast cancer is the most common form of cancer and the focus on finding chemotherapeutic agents have recently shifted to natural products. Piper betle is a medicinal plant with various biological activities. However, not much data is available on the anti-cancer effects of P. betle on breast cancer. Due to the current interest in the potential effects of antioxidants from natural products in breast cancer treatment, we investigated the antioxidant activities of the leaves of P. betle and its inhibitory effect on the proliferation of the breast cancer cell line, MCF-7.

Methods

The leaves of P. betle were extracted with solvents of varying polarities (water, methanol, ethyl acetate and hexane) and their phenolic and flavonoid content were determined using colorimetric assays. Phenolic composition was characterized using HPLC. Antioxidant activities were measured using FRAP, DPPH, superoxide anion, nitric oxide and hyroxyl radical scavenging assays. Biological activities of the extracts were analysed using MTT assay and antioxidant enzyme (catalase, superoxide dismutase, glutathione peroxidase) assays in MCF-7 cells.

Results

Overall, the ethyl acetate extract showed the highest ferric reducing activity and radical scavenging activities against DPPH, superoxide anion and nitric oxide radicals. This extract also contained the highest phenolic content implying the potential contribution of phenolics towards the antioxidant activities. HPLC analyses revealed the presence of catechin, morin and quercetin in the leaves. The ethyl acetate extract also showed the highest inhibitory effect against the proliferation of MCF-7 cells (IC50=65 μg/ml). Treatment of MCF-7 cells with the plant extract increased activities of catalase and superoxide dismutase.

Conclusions

Ethyl acetate is the optimal solvent for the extraction of compounds with antioxidant and anti-proliferative activities. The increased activities of catalase and superoxide dismutase in the treated cells could alter the antioxidant defense system, potentially contributing towards the anti-proliferative effect. There is great potential for the ethyl acetate extract of P. betle leaf as a source of natural antioxidants and to be developed as therapeutics in cancer treatment.

【 授权许可】

   
2012 Abrahim et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20151109192037798.pdf 379KB PDF download
Figure 3. 76KB Image download
Figure 2. 29KB Image download
Figure 1. 39KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】
  • [1]Seeram NP, Zhang Y, Nair MG: Inhibition of Proliferation of Human Cancer Cells and Cyclooxygenase Enzymes by Anthocyanidins and Catechins. Nutr Cancer 2003, 46:101-106.
  • [2]Thangapazham RL, Singh AK, Sharma A, Warren J, Gaddipati JP, Maheshwari RK: Green tea polyphenols and its constituent epigallocatechin gallate inhibits proliferation of human breast cancer cells in vitro and in vivo. Cancer Lett 2007, 245:232-241.
  • [3]Li WY, Chan SW, Guo DJ, Yu PHF: Correlation Between Antioxidative Power and Anticancer Activity in Herbs from Traditional Chinese Medicine Formulae with Anticancer Therapeutic Effect. Pharm Biol 2007, 45:541-546.
  • [4]Ahmad I, Mehmood Z, Mohammad F: Screening of some Indian medicinal plants for their antimicrobial properties. J Ethnopharmacol 1998, 62:183-193.
  • [5]Gilani AH, Atta Ur R: Trends in ethnopharmacology. J Ethnopharmacol 2005, 100:43-49.
  • [6]Somanadhan B, Varughese G, Palpu P, Sreedharan R, Gudiksen L, Wagner Smitt U, Nyman U: An ethnopharmacological survey for potential angiotensin converting enzyme inhibitors from Indian medicinal plants. J Ethnopharmacol 1999, 65:103-112.
  • [7]Jeng JH, Chen SY, Liao CH, Tung YY, Lin BR, Hahn LJ, Chang MC: Modulation of platelet aggregation by areca nut and betel leaf ingredients: roles of reactive oxygen species and cyclooxygenase. Free Radic Biol Med 2002, 32:860-871.
  • [8]Arambewela LSR, Arawwawala LDAM, Ratnasooriya WD: Antidiabetic activities of aqueous and ethanolic extracts of Piper betle leaves in rats. J Ethnopharmacol 2005, 102:239-245.
  • [9]Singh M, Shakya S, Soni VK, Dangi A, Kumar N, Bhattacharya SM: The n-hexane and chloroform fractions of Piper betle L. trigger different arms of immune responses in BALB/c mice and exhibit antifilarial activity against human lymphatic filarid Brugia malayi. Int Immunopharmacol 2009, 9:716-728.
  • [10]Wirotesangthong M, Inagaki N, Tanaka H, Thanakijcharoenpath W, Nagai H: Inhibitory effects of Piper betle on production of allergic mediators by bone marrow-derived mast cells and lung epithelial cells. Int Immunopharmacol 2008, 8:453-457.
  • [11]Dasgupta N, De B: Antioxidant activity of Piper betle L. leaf extract in vitro. Food Chem 2004, 88:219-224.
  • [12]Majumdar B, Chaudhuri S, Ray A, Bandyopadhyay S: Potent antiulcerogenic activity of ethanol extract of leaf of Piper betle Linn. by antioxidative mechanism. Indian J Clin Biochem 2002, 17:49-57.
  • [13]Rao AR, Sinha A, Selvan RS: Inhibitory action of Piper betle on the initiation of 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis in rats. Cancer Lett 1985, 26:207-214.
  • [14]Murakami A, Ali AM, Mat-Salleh K, Koshimizu K, Ohigashi H: Screening for the In Vitro Anti-tumor-promoting Activities of Edible Plants from Malaysia. Biosci Biotechnol Biochem 2000, 64:9-16.
  • [15]Fathilah RA, Sujata R, Norhanom AW, Adenan MI: Antiproliferative activity of aqueous extract of Piper betle L. and Psidium guajava L. on KB and HeLa cell lines. Planta Med 2010, 4:987-990.
  • [16]Wong SP, Leong LP, William Koh JH: Antioxidant activities of aqueous extracts of selected plants. Food Chem 2006, 99:775-783.
  • [17]Singleton VL, Rossi JA: Colorimetry of Total Phenolics with Phosphomolybdic-Phosphotungstic Acid Reagents. Am J Enol Viticult 1965, 16:144-158.
  • [18]Chang CC, Yang MH, Wen HM, Chern JC: Estimation of Total Flavonoid Content in Propolis by Two Complementary Colorimetric Methods. J Food Drug Anal 2002, 10:178-182.
  • [19]Benzie IFF, Strain JJ: The Ferric Reducing Ability of Plasma (FRAP) as a Measure of “Antioxidant Power”: The FRAP Assay. Anal Biochem 1996, 239:70-76.
  • [20]Siddhuraju P, Becker K: The antioxidant and free radical scavenging activities of processed cowpea (Vigna unguiculata (L.) Walp.) seed extracts. Food Chem 2007, 101:10-19.
  • [21]Rai S, Wahile A, Mukherjee K, Saha BP, Mukherjee PK: Antioxidant activity of Nelumbo nucifera (sacred lotus) seeds. J Ethnopharmacol 2006, 104:322-327.
  • [22]Razali N, Mat-Junit S, Abdul-Muthalib AF, Subramaniam S, Abdul-Aziz A: Effects of various solvents on the extraction of antioxidant phenolics from the leaves, seeds, veins and skins of Tamarindus indica L. Food Chem 2012, 131:441-448.
  • [23]Borras Linares I, Arraez-Roman D, Herrero M, Ibanez E, Segura-Carretero A, Fernandez-Gutierrez A: Comparison of different extraction procedures for the comprehensive characterization of bioactive phenolic compounds in Rosmarinus officinalis by reversed-phase high-performance liquid chromatography with diode array detection coupled to electrospray time-of-flight mass spectrometry. J Chromatogr A 2011, 1218:7682-7690.
  • [24]Krizmana M, Baricevic D, Prosek M: Determination of phenolic compounds in fennel by HPLC and HPLC-MS using a monolithic reversed-phase column. J Pharm Biomed Anal 2007, 43:481-485.
  • [25]Fu L, Xu BT, Xu XR, Gan RY, Zhang Y, Xia EQ, Li HB: Antioxidant capacities and total phenolic contents of 62 fruits. Food Chem 2011, 129:345-350.
  • [26]Razab R, Abdul-Aziz A: Antioxidants from tropical herbs. Nat Prod Commun 2010, 5:441-445.
  • [27]Wolfe KL, Liu RH: Structure-Activity Relationships of Flavonoids in the Cellular Antioxidant Activity Assay. J Agric Food Chem 2008, 56:8404-8411.
  • [28]Bhattacharya S, Subramanian M, Roychowdhury S, Bauri AK, Kamat JP, Chattopadhyay S, Bandyopadhyay SK: Radioprotective Property of the Ethanolic Extract of Piper betel Leaf. J Radiat Res 2005, 46:165-171.
  • [29]Parmar VS, Jain SC, Gupta S, Talwar S, Rajwanshi VK, Kumar R, Azim A, Malhotra S, Kumar N, Jain R, Sharma NK, Tyagi OD, Lawrie SL, Errington W, Howarth OW, Olsen CE, Singh SK, Wengel J: Polyphenols and alkaloids from piper species. Phytochemistry 1998, 49:1069-1078.
  • [30]Chang MC, Uang BJ, Wu HL, Lee JJ, Hahn LJ, Jeng JH: Inducing the cell cycle arrest and apoptosis of oral KB carcinoma cells by hydroxychavicol: roles of glutathione and reactive oxygen species. Br J Pharmacol 2002, 135:619-630.
  • [31]Rathee JS, Patro BS, Mula S, Gamre S, Chattopadhyay S: Antioxidant Activity of Piper betel Leaf Extract and Its Constituents. J Agric Food Chem 2006, 54:9046-9054.
  • [32]Ye F, Xui L, Yi J, Zhang W, Zhang DY: Anticancer activity of Scutellaria baicalensis and its potential mechanism. J Altern Complement Med 2002, 8:567-572.
  • [33]Chiu LCM, Ho TS, Wong EYL, Ooi VEC: Ethyl acetate extract of Patrinia scabiosaefolia downregulates anti-apoptotic Bcl-2/Bcl-XL expression, and induces apoptosis in human breast carcinoma MCF-7 cells independent of caspase-9 activation. J Ethnopharmacol 2006, 105:263-268.
  • [34]Franco R, Schoneveld O, Georgakilas AG, Panayiotidis MI: Oxidative stress, DNA methylation and carcinogenesis. Cancer Lett 2008, 266:6-11.
  • [35]Haklar G, Sayin-Ozveri E, Yuksel M, Aktan AO, Yalcin AS: Different kinds of reactive oxygen and nitrogen species were detected in colon and breast tumors. Cancer Lett 2001, 165:219-224.
  • [36]Petit E, Courtin A, Kloosterboer HJ, Rostene W, Forgez P, Gompel A: Progestins induce catalase activities in breast cancer cells through PRB isoform: Correlation with cell growth inhibition. J Steroid Biochem Mol Biol 2009, 115:153-160.
  • [37]Gibanananda R, Batra S, Shukla NK, Deo S, Raina V, Ashok S, Husain SA: Lipid peroxidation, free radical production and antioxidant status in breast cancer. Breast Cancer Res Treat 2000, 59:163-170.
  • [38]Punnonen K, Ahotupa M, Asaishi K, Hyöty M, Kudo R, Punnonen R: Antioxidant enzyme activities and oxidative stress in human breast cancer. J Cancer Res Clin Oncol 1994, 120:374-377.
  • [39]Ishii K, Zhen LX, Wang DH, Funamori Y, Ogawa K, Taketa K: Prevention of Mammary Tumorigenesis in Acatalasemic Mice by Vitamin E Supplementation. Cancer Sci 1996, 87:680-684.
  • [40]Glorieux C, Dejeans N, Sid B, Beck R, Calderon PB, Verrax J: Catalase overexpression in mammary cancer cells leads to a less aggressive phenotype and an altered response to chemotherapy. Biochem Pharmacol 2011, 82:1384-1390.
  • [41]Sun Y: Free radicals, antioxidant enzymes, and carcinogenesis. Free Rad Biol Med 1990, 8:583-599.
  • [42]Xu Y, Krishnan A, Wan XS, Majima H, Yeh CC, Ludewig G, Kasarskis EJ, St Clair DK: Mutations in the promoter reveal a cause for the reduced expression of the human manganese superoxide dismutase gene in cancer cells. Oncogene 1999, 18:93-102.
  • [43]Ridnour LA, Oberley TD, Oberley LW: Tumor Suppressive Effects of MnSOD Overexpression May Involve Imbalance in Peroxide Generation Versus Peroxide Removal. Antioxid Redox Signal 2004, 6:501-512.
  • [44]Li Z, Khaletskiy A, Wang J, Wong JYC, Oberley LW, Li JJ: Genes regulated in human breast cancer cells overexpressing manganese-containing superoxide dismutase. Free Rad Biol Med 2001, 30:260-267.
  • [45]Li JJ, Oberley LW, Fan M, Colburn NH: Inhibition of AP-1and NF-κB by manganese-containing superoxide dismutase in human breast cancer cells. FASEB J 1998, 12:1713-1723.
  • [46]Brigelius-Flohe R, Kipp A: Glutathione peroxidases in different stages of carcinogenesis. Biochim Biophys Acta 2009, 1790:1555-1568.
  • [47]Heirman I, Ginneberge D, Brigelius-Flohe R, Hendrickx N, Agostinis P, Brouckaert P, Rottiers P, Grooten J: Blocking tumor cell eicosanoid synthesis by GPx4 impedes tumor growth and malignancy. Free Rad Biol Med 2006, 40:285-294.
  • [48]Seeram NP, Adams LS, Zhang Y, Lee R, Sand D, Scheuller HS, Heber D: Blackberry, Black Raspberry, Blueberry, Cranberry, Red Raspberry, and Strawberry Extracts Inhibit Growth and Stimulate Apoptosis of Human Cancer Cells In Vitro. J Agric Food Chem 2006, 54:9329-9339.
  • [49]Lei D, Chan CP, Wang YJ, Wang TM, Lin BR, Huang CH, Lee JJ, Chen HM, Jeng JH, Chang MC: Antioxidative and antiplatelet effects of aqueous inflorescence Piper betle extract. J Agric Food Chem 2003, 51:2083-2088.
  • [50]Wang S, Meckling KA, Marcone MF, Kakuda Y, Tsao R: Can phytochemical antioxidant rich foods act as anti-cancer agents? Food Res Int 2011, 44:2545-2554.
  文献评价指标  
  下载次数:5次 浏览次数:4次