Browse > Article
http://dx.doi.org/10.7314/APJCP.2016.17.1.315

Antiproliferative Evaluation and Apoptosis Induction in MCF-7 Cells by Ziziphus spina christi Leaf Extracts  

Farmani, Fatemeh (Medicinal Plants Processing Research Center, School of Pharmacy, Shiraz University of Medical Sciences)
Moein, Mahmoodreza (Medicinal Plants Processing Research Center, School of Pharmacy, Shiraz University of Medical Sciences)
Amanzadeh, Amir (National Cell Bank of Iran, Pasteur Institute of Iran)
Kandelous, Hirsa Mostafapour (Department of Physiology and Pharmacology, Pasteur Institute of Iran)
Ehsanpour, Zahra (Department of Physiology and Pharmacology, Pasteur Institute of Iran)
Salimi, Mona (Department of Physiology and Pharmacology, Pasteur Institute of Iran)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.17, no.1, 2016 , pp. 315-321 More about this Journal
Abstract
Background: Herbal medicine has becoming a potential source of treatment for different types of cancer including breast cancer. It has been shown that plants from the family Rhamnaceae possess anticancer activity. Objective: In this study, we determined the antiproliferative influence of Ziziphus spina christi- a species from this family- on the MCF-7 (human breast adenocarcinoma) cell line. Materials and Methods: The cytotoxicity of the total extract, ethanol, ethanol-aqueous (1:1) as well as aqueous fractions of Ziziphus spina christi leaves was evaluated through MTT assay against MCF-7 cell line. Cell cycle inhibition and apoptosis induction were assessed by flowcytometry cycle RNase/PI analysis and Annexin V-FLUOS, respectively. Apoptosis was also analyzed by immunoblotting assay. Results: Our results indicated that the ethanolic fraction had the lowest $IC_{50}$ value (0.02 mg/ml), induced cell cycle arrest at the G1/S phase as well as apoptosis after a 48h of treatment. Conclusions: This is the first report on anticancer effect of Ziziphus spina christi ethanolic fraction on breast cancer cells, providing a scientific basis for its utility in traditional medicine. However, further in-depth studies are needed to confirm the precise mechanisms.
Keywords
Ziziphus spina christi; anticancer influence; MCF-7; cell cycling; apoptosis;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Abalaka ME, Daniyan SY, Mann A (2010). Evaluation of the antimicrobial activities of two Ziziphus species (Ziziphus mauritiana L. and Ziziphus spinachristi L.) on some microbial pathogens. Afr J pharm pharmacol, 4, 135-9.
2 Abrahim NN, Kanthimathi M, Abdul-Aziz A (2012). Piper betle shows antioxidant activities, inhibits MCF-7 cell proliferation and increases activities of catalase and superoxide dismutase. BMC Complement Alternat Med, 12, 220.   DOI
3 Adzu B, Amos S, Amizan M, Gamaniel K (2003). Evaluation of the antidiarrhoeal effects of Zizyphus spina-christi stem bark in rats. J Acta Trop, 87, 245-50.   DOI
4 Ali-Shtayeh M, Yaghmour RM-R, Faidi Y, et al (1998). Antimicrobial activity of 20 plants used in folkloric medicine in the Palestinian area. J Ethnopharm, 60, 265-71.   DOI
5 Alshawsh MA, Abdulla MA, Ismail S, et al (2012). Free radical scavenging, antimicrobial and immunomodulatory activities of orthosiphon stamineus. J Art Mol, 17, 5385-95.
6 Asgarpanah J, Haghighat E (2012). Phytochemistry and pharmacologic properties of Ziziphus spina christi (L.) Willd. Afr J Pharm & Pharmacol, 6, 2332-9.
7 Beeran AA, Maliyakkal N, Rao CM, Udupa N (2015). The enriched fraction of Elephantopus scaber Triggers apoptosis and inhibits multi-drug resistance transporters in human epithelial cancer cells. Pharmacogn Mag, 11, 257.   DOI
8 Brantner AH, Males Z (1999). Quality assessment of Paliurus spina-christi extracts. J Ethnopharmacol, 66, 175-9.   DOI
9 Brown D (1995). Encyclopaedia of herbs and their uses. london: dorling kindersley.
10 Chan ASL, Yip EC-H, Yung LY, et al (2005). Immuno-regulatory effects of CKBM on the activities of mitogen-activated protein kinases and the release of cytokines in THP-1 monocytic cells. Bio Pharm Bull, 28, 1645-50.   DOI
11 Chandra D, Liu J-W, Tang DG (2002). Early mitochondrial activation and cytochrome c up-regulation during apoptosis. J Biol Chem, 277, 50842-54.   DOI
12 Cheng X, Xiao Y, Wang X, et al (2012). Anti-tumor and pro-apoptotic activity of ethanolic extract and its various fractions from Polytrichum commune L. ex Hedw in L1210 cells. J Ethno Pharmacol, 143, 49-56.   DOI
13 Cragg GM, Newman DJ (2005). Plants as a source of anti-cancer agents. J Ethnopharmacol, 100, 72-79.   DOI
14 Demain AL, Vaishnav P (2011). Natural products for cancer chemotherapy. Microb biotech, 6, 687-99.
15 Esteves-Souza A, Silva TM, Alves CCF, et al (2002). Cytotoxic activities against Ehrlich carcinoma and human K562 leukaemia of alkaloids and flavonoid from two Solanum species. J Braz Chem Soc, 13, 838-42.   DOI
16 Gao G, Dou QP (2000). G1 phase-dependent expression of Bcl-2 mRNA and protein correlates with chemoresistance of human cancer cells. Mol Pharmacol, 58, 1001-10.   DOI
17 Ghannadi A, Tavakoli N, Mehri-Ardestani M (2003). Volatile constituents of the leaves of Ziziphus spina-christi (L.) Willd. from Bushehr, Iran. J Essen Oil Res, 15, 191-2.   DOI
18 Godini A, Kazem M, Naseri G, Badavi M (2009). The effect of Zizyphus Spina-Christi leaf extract on the isolated rat aorta. J Pak Med Assoc, 59, 537-9.
19 Him-Che Y (1985). Handbook of Chinese herbs and formulas. Losangeles, CA: Institute of Chinese Medicine.
20 Huang X, Kojima-Yuasa A, Norikura T, et al (2007). Mechanism of the anti-cancer activity of Zizyphus jujuba in HepG2 cells. Am J Chin Med, 35, 517-32.   DOI
21 Huang X, Kojima-Yuasa A, Xu S, et al (2009). Combination of Zizyphus jujuba and green tea extracts exerts excellent cytotoxic activity in HepG2 cells via reducing the expression of APRIL. Am J Chin Med, 37, 169-79.   DOI
22 Jafarian A, Zolfaghari B, Shirani K (2014). Cytotoxicity of different extracts of arial parts of Ziziphus spina-christi on HeLa and MDA-MB-468 tumor cells. Adv Biomed Res, 3, 38.   DOI
23 Jain R, Jain SK (2011). Screening of cytotoxic activity of some medicinal plants used traditionally to treat cancer in Chhattisgarh state, India. Asian Pac J Trop Biomed, 1, 147-50.   DOI
24 Karimi E, Oskoueian E, Hendra R, et al (2012). Phenolic compounds characterization and biological activities of citrus aurantium bloom. Molecules, 17, 1203-18.   DOI
25 Karon B, Ibrahim M, Mahmood A, et al (2011). Preliminary antimicrobial, cytotoxic and chemical investigations of averrhoa bilimbi linn. and Zizyphus mauritiana Lam. Bangladesh Pharm J, 14, 127-31.
26 Krifa M, Alhosin M, Muller CD, et al (2013). Limoniastrum guyonianum aqueous gall extract induces apoptosis in human cervical cancer cells involving p16 INK4A re-expression related to UHRF1 and DNMT1 down-regulation. J Exp Clin Cancer Res, 32, 30-40.   DOI
27 Kumar H, Kim I-S, More SV, et al (2013). Gastrodin protects apoptotic dopaminergic neurons in a toxin-induced Parkinson's disease model. Evid Based Complement Alternat Med, 2013, 514095.
28 Lee SM, Min BS, Lee C-G, et al (2003). Cytotoxic triterpenoids from the fruits of Zizyphus jujuba. Planta medica, 69, 1051-4.   DOI
29 Malik S, Cusido RM, Mirjalili MH, et al (2011). Production of the anticancer drug taxol inTaxus baccata suspension cultures: A review. Proc Biochem, 46, 23-34.   DOI
30 Meng FM, Yang JB, Yang CH, et al (2012). Vitexicarpin induces apoptosis in human prostate carcinoma PC-3 cells through G2/M phase arrest. Asian Pac J Cancer Prev, 13, 6369-74.   DOI
31 Michel CG, Nesseem DI, Ismail MF (2011). Anti-diabetic activity and stability study of the formulated leaf extract of Zizyphus spina-christi (L.) Willd with the influence of seasonal variation. J Ethnopharmacol, 133, 53-62.   DOI
32 Mishra T, Khullar M, Bhatia A (2010). Anticancer potential of aqueous ethanol seed extract of Ziziphus mauritiana against cancer cell lines and Ehrlich ascites carcinoma. J Evid Based Complement Alternt Med, 8, 101-111.
33 Mohan S, Abdelwahab SI, Kamalidehghan B, et al (2012). Involvement of NF-${\kappa}B$ and Bcl2/Bax signaling pathways in the apoptosis of MCF7 cells induced by a xanthone compound Pyranocycloartobiloxanthone A. Phytomedicine, 19, 1007-15.   DOI
34 Ng WK, Yazan LS, Ismail M (2011). Thymoquinone from Nigella sativa was more potent than cisplatin in eliminating of SiHa cells via apoptosis with down-regulation of Bcl-2 protein. Toxicol in vitro, 25, 1392-8.   DOI
35 Pieme CA, Santosh G, Tekwu E, et al (2014). Fruits and barks extracts of Zanthozyllum heitzii a spice from Cameroon induce mitochondrial dependent apoptosis and Go/G1 phase arrest in human leukemia HL-60 cells. Biol Res, 47, 1-13.
36 Plastina P, Bonofiglio D, Vizza D, et al (2012). Identification of bioactive constituents of Ziziphus jujube fruit extracts exerting antiproliferative and apoptotic effects in human breast cancer cells. J Ethnopharmacol, 140, 325-32.   DOI
37 Pratt MC, White D, Kushwaha N, et al (2007). Cytoplasmic mutant p53 increases Bcl-2 expression in estrogen receptorpositive breast cancer cells. Apoptosis, 12, 657-69.   DOI
38 Quadri MFA, Saleh MS, Alsanosy R, et al (2014). Effectiveness of an intervention program on knowledge of oral cancer among the youth of Jazan, Saudi Arabia. Asian Pac J Cancer Prev, 15, 1913-8.   DOI
39 Ren W, Qiao Z, Wang H, et al (2003). Flavonoids: promising anticancer agents. Med Res Rev, 23, 519-34.   DOI
40 Richardson JE, Fay MF, Cronk QC, et al (2000). A phylogenetic analysis of Rhamnaceae using rbcL and trnL-F plastid DNA sequences. Am J Bot, 87, 1309-24.   DOI
41 Rosas L, Cordeiro MS, Campos FR, et al (2007). In vitro evaluation of the cytotoxic and trypanocidal activities of Ampelozizyphus amazonicus (Rhamnaceae). Braz J Med Biol Res, 40, 663-70.   DOI
42 Saif MW, Lansigan F, Ruta S, et al (2010). Phase I study of the botanical formulation PHY906 with capecitabine in advanced pancreatic and other gastrointestinal malignancies. Phytomedicine, 17, 161-9.   DOI
43 Silva ERd, Diedrich D, Bolzan RC, Giacomelli SR (2012). Toxicological and pharmacological evaluation of Discaria americana Gillies & Hook (Rhamnaceae) in mice. J Pharm Sci, 48, 273-80.
44 Srivastava V, Negi AS, Kumar J, et al (2005). Plant-based anticancer molecules: a chemical and biological profile of some important leads. Bioorg Med Chem, 13, 5892-908.   DOI
45 Tasyriq M, Najmuldeen IA, In LL, et al (2012). $7{\alpha}$-Hydroxy-${\beta}$Sitosterol from Chisocheton tomentosus induces apoptosis via dysregulation of cellular Bax/Bcl-2 ratio and cell cycle arrest by downregulating ERK1/2 activation. Evid Based Complement Alternat Med, 765316.
46 Teijido O, Dejean L (2010). Upregulation of Bcl2 inhibits apoptosis-driven BAX insertion but favors BAX relocalization in mitochondria. FEBS letters, 584, 3305-10.   DOI
47 Thirumal M, Kishore G, Surya S (2013). Antiproliferative activity of various parts of Tecoma stans (L.) against human breast cancer cells in vitro Res. J Pharm Biol Chem Sci, 4, 305-13.
48 Vahedi F, Najafi MF, Bozari K (2008). Evaluation of inhibitory effect and apoptosis induction of Zyzyphus Jujube on tumor cell lines, an in vitro preliminary study. Cytotech, 56, 105-111.   DOI
49 Veeresh SK (2010). Anthelmintic activity of Zizyphus jujuba Mill & Lamk. J Pharm Bio Sci, 2, 63-65.   DOI
50 Wu G, Qian Z, Guo J, et al (2012). Ganoderma lucidum extract induces G1 cell cycle arrest, and apoptosis in human breast cancer cells. Am J Chin Med, 40, 631-642.   DOI