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http://dx.doi.org/10.7314/APJCP.2015.16.17.7641

Antitumoral and Antioxidant Potential of Egyptian Propolis Against the PC3 Prostate Cancer Cell Line  

Salim, Elsayed I (Department of Zoology, Faculty of Science, Tanta University, Research Lab. of Molecular Carcinogenesis)
Abd El-Magid, Afaf D (Department of Biochemistry & Clinical Chemistry, Moshtohor, Benha University)
Farara, Khalid M (Department of Clinical Pathology, Faculty of Veterinary Medicine, Moshtohor, Benha University)
Maria, Dina SM (Department of Zoology, Faculty of Science, Tanta University, Research Lab. of Molecular Carcinogenesis)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.17, 2015 , pp. 7641-7651 More about this Journal
Abstract
It has been shown previously that nutritional supplements rich in polyphenolic compounds play a significant role in prostate cancer chemoprevention. Propolis is a natural, resinous hive product that has several pharmacological activities including antimicrobial, antioxidant, anti-inflammatory, and antitumoral activities. The aim of this study was to compare the cytotoxic, antioxidant and antitumoral activities of an ethanolic extract of Egyptian propolis (EEP) in vitro with an established chemotherapeutic drug such as doxorubicin (DOX), and the effects of their combination against the PC3 human prostate cancer cell line. Cellular viability and $IC_{50}$ levels with EEP, DOX and their (v/v) combination were detected by sulphorhodamine-B (SRB) assay after incubation of PC3 cells for 72h with different doses (0, 0.01, 0.1, 1, 10 and $100{\mu}g/ml$). Two selected doses of $IC_{50}$ and $IC_{25}$ were applied to cells for 24h for antitumor evaluation assay of treatment compounds. EEP and its (v/v) combination with DOX showed significant antitumor potential besides high antioxidant properties of superoxide dismutase (SOD), total antioxidant capacity (TAC), catalase (CAT), nitric oxide (NO) and reduced glutathione (GSH) levels when compared with the control untreated cells. DNA fragmentation assay and semi quantitative RT-PCR analyses for p53 and Bax genes showed that EEP activated cellular apoptosis and increased the mRNA expression levels more than other treatment. In conclusion, EEP alone or in combination with DOX at both doses used here showed greater antioxidant, antiproliferative and apoptotic effects against the PC3 cell lines as compared to treatment with DOX alone. Therefore, EEP could be considered as a promising candidate for prostate cancer chemotherapy.
Keywords
Propolis; prostate cancer; PC3 cell line; p53; Bax; oxidative stress; apoptosis;
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1 Abd El-Hady FK, Hegazi AG (1994). Gas chromatography -mass spectrometry (GC/MS) study of the Egyptian propolis 1-aliphatic, phenolic acids and their esters. Egypt J Appl Sci, 9, 749-60.
2 Abozid MM, Ahmed AA (2013). Chemical composition of Egyptian and commercial propolis and its effects on liver function and lipid profiles in albino rats. J Biological Chem. Env Res, 8, 323-40.
3 Adams JM, Cory S (1998). The bcl-2 protein family, Arbiters of cell survival. Science, 281, 1322-6.   DOI
4 Akyol S, Ugurcu V, Balci M, et al (2014). Caffeic acid phenethyl ester, its protective role against certain major eye diseases. J Ocul Pharmacol Ther, 30, 700-8.   DOI
5 Alyane M, Kebsa LB, Boussenane H, et al (2008). Cardioprtective effects and mechanism of action of poly phenols extracted from propolis against doxorubicin toxicity. Pak J pharm Sci, 1, 20-9.
6 Aso K, Kanno S, Tadano T, et al (2004). Inhibitory effect of propolis on the growth of human leukemic U937. Biol Pharm Bull, 27, 727-30.   DOI
7 Atsushi K, Mutsuo F, Manabu M, et al (2001). Expression of Bax and apoptosis-related proteins in human esophageal squamous cell carcinoma including dysplasia. Canadian Academy Pathol, 14, 741-7.
8 Baillie JK, Thompson AAR, Irving JB, et al (2009). Oral antioxidant supplementation does not prevent acute mountain sickness, double blind randomized placebocontrolled trial. QJM, Int J Med, 102, 341-8.   DOI
9 Begnini KR, Moura de Leon PM, Thurow H, et al (2014). Brazilian red propolis induces apoptosis-like cell death and decreases migration potential in bladder cancer cells. Evid Based Complement Alternat Med, 2014, 639856.
10 Beutler E, Dunning D, Dabe IB, et al (1988). Erythrocyte glutathione S-transferase deficiency and hemolytic anemia. Blood, 72, 73-7.
11 Chaabane W, User SD, El-Gazzah M, et al (2013). Autophagy, apoptosis, mitoptosis and necrosis, interdependence between those pathways and effects on cancer. Arch Immunol Ther Exp (Warsz), 61, 43-58.   DOI
12 Chan GC, Cheung KW, Sze DM. (2013). The immunomodulatory and anticancer properties of propolis. Clin Rev Allergy Immunol, 44, 262-73.   DOI
13 Chen CN, Wu CL, Lin JK (2007). Apoptosis of human melanoma cells induced by the novel compounds propolin A and propolin B from Taiwenese propolis. Cancer Lett, 245, 218-31.   DOI
14 Chen MJ, Chang WH, Lin CC, et al (2008). Caffeic acid phenethyl ester induces apoptosis of human pancreatic cancer cells involving caspase and mitochondrial dysfunction. Pancreatol, 8, 566-76.   DOI
15 Christine ME, Martine FR, Stanley JK, et al (2001). Bax loss impairs myc-induced apoptosis and circumvents the selection of p53 mutations during myc-mediated lymphomagenesis. Mol Cell Biol, 21, 7653-62.   DOI
16 Daugsch A, Moraes CS, Fort P, et al (2008). Brazilian red propolis chemical composition and botanical origin. Evid Based Comp Alternat Med, 5, 435-41.   DOI
17 Goel M, Eraslan G, Silici S (2009). Antioxidant effect of propolis against exposure to propetamphos in rats. Ecotoxicol. Environ Safety, 72, 900-915.
18 Harris SR, Panaro NJ, Thorgeirsson UP (2000). Oxidative stress contributes to the anti-proliferative effects of flavone acetic acid on endothelial cells. Anticancer Res, 20, 2249-54.
19 Janicke RU, Sohn D, Schulze-Osthoff K (2008). The dark side of a tumor suppressor, anti-apoptotic p53. Cell Death Differ, 15, 959-76.   DOI
20 Hilger RA, Richly H, Grubert M, et al (2005). Pharmacokinetics (PK) of a liposomal encapsulated fraction containing doxorubicin and of doxorubicin released from the liposomal capsule after intravenous infusion of Caelyx/Doxil. Int J Clin Pharmacol Ther, 43, 588.   DOI
21 Jasprica I, Mornar A, Debeljak Z, et al (2007). In vivo study of propolis supplementation effects on antioxidative status and red blood cells. J Ethnopharmacol, 110, 548-54.   DOI
22 Kasala ER, Bodduluru LN, Madana RM, et al (2015). Chemopreventive and therapeutic potential of chrysin in cancer, mechanistic perspectives. Toxicol Lett, 233, 214-25.   DOI
23 Khalil ML (2006). Biological activity of bee propolis in health and disease, Asian Pac J Cancer Prev, 7, 22-31.
24 Kimoto T, Arai S, Kohguchi M, et al (1998). Apoptosis and suppression of tumor growthby artepillin C extracted from Brazilian propolis. Cancer Detect Prev, 22, 506-15.   DOI
25 Kimoto T, Aga M, Hino K, et al (2001). Apoptosis of human leukemia cells induced by Artepillin C, an active ingredient of Brazilian propolis. Anticancer Res, 21, 221-8.
26 Kujumgiev A, Tsvetkova I, Serkedjieva Y, et al (1999). Antibacterial, antifungal and antiviral activity of propolis of different geographic origin. J Ethnopharmacol, 64, 235-240.   DOI
27 Kumazawa S, Hamasaka T, Nakayama T. (2004). Antioxidant activity of propolis of various geographic origins. Food Chem, 84, 329-39.   DOI
28 Marghitas AL, Dezmirean D, Moise A, et al (2009). DPPH method for evaluation of propolis antioxidant activity. Bulletin UASVM Animal Sci Biotechnol, 66, 253-8.
29 Leist M, Jaattela M (2001). Four deaths and a funeral, from caspases to alternative mechanisms. Nature Rev Molecular Cell Biol, 2, 589-98.
30 Marghitas LA, Laslo L, Dezmirean D, et al (2007). Total phenolics and antioxidant activity of romanian propolis. international conference agricultural and food sciences, progresses and technologies, sibiu, romania, 209-12.
31 Markiewicz-Ukowska R, Borawska MH, Fiedorowicz A, et al (2013). Propolis changes the anticancer activity of temozolomide in U87MG human glioblastoma cell line. BMCComplement Altern Med, 13, 50.   DOI
32 Mishima S, Narita Y, Chikamatsu S (2005). Effects of propolis on cell growth and gene expression in HL-60 cells. J Ethnopharmacol, 99, 5-11.   DOI
33 Montgomery JF, Hum S (1995). Field diagnosis of nitrite poisoning in cattle by testing aqueous humour samples with urine test strips. Vet Rec, 137, 593-4.
34 Moreira L, Dias LG, Pereira JA, et al (2008). Antioxidant properties, total phenols and pollen analysis of propolis samples from Portugal. Food Chem Toxicol, 46, 3482-85.   DOI
35 Motomura MK, Won KM, Suh SJ, et al (2008). Propolis induces cell cycle arrest and apoptosis in human leukemic U937 cells through Bcl-2/Bax regulation. Environ Toxicol Pharmacol, 26, 61-7.   DOI
36 Murtaza G, Karim S, Akram MR, et al (2014). Caffeic acid phenethyl ester and therapeutic potentials. Biomed Res Int, 145342, 9.
37 Quinn M, Babb P (2002). Patterns and trends in prostate cancer incidence, survival, prevalence and mortality. Part I, International comparisons. BJU Int, 90, 162-73.   DOI
38 Orsatti CL, Missima F, Pagliarone AC, et al (2010). Propolis immunomodulatory action in vivo on Toll-like receptors 2 and 4 expression and on pro-inflammatory cytokines production in mice. Phytotherapy Res, 24, 1141-6.
39 Orsolic N, Horvatknezevic A, Benkovic V, et al (2008). Benefits of use of propolis and related flavonoids against the toxicity of chemotherapeutic agents. in orsolic, n; basic, i (eds). ethnopharmacology- review book. Res Signpost India, 195-222.
40 Orsolic N (2010). A review of propolis antitumour action in vivo and in vitro. J Api Productand Ap Med Sci, 2, 1-20.   DOI
41 Sabir SM, Ahmad SD, Abdul H, et al (2012). Antioxidant and Hepatoprotective activity of ethanolic extract of leaves of Solidago microglossa containing polyphenolic compounds. Food Chem, 131, 741-7.   DOI
42 Salim EI, Jazieh AR, Moore MA (2011). Lung cancer incidence in the Arab league countries, risk factors and control. Asian Pac J Cancer Prev, 12, 17-34.
43 Samarghandian S, Shabestari MM (2013). DNA fragmentation and apoptosis induced by safranal in human prostate cancer cell line. Indian J Urol 29, 177-83   DOI
44 Samarghandian S, Borji A, Delkhosh MB, et al. (2013). Safranal treatment improves hyperglycemia, hyperlipidemia and oxidative stress in streptozotocin-induced diabetic rats. J Pharm Pharm Sci, 16, 352-62.   DOI
45 Samini F, Samarghandian S, Borji A, et al (2013). Curcumin pretreatment attenuates brain lesion size and improves neurological function following traumatic brain injury in the rat. Pharmacol Biochem Behav, 110, 238-44.   DOI
46 Siddhuraju P (2006). The antioxidant activity and free radicalscavenging capacity of phenolics of raw and dry heated moth bean. (Vigna aconitifolia) (Jacq.) Marcchal seed extracts, 99, 149-57.   DOI
47 Scheller S, Krol W, Swiacik J, et al (1989). Antitumoral property of ethanolic extract of propolis in mice-bearing Ehrlich carcinoma, as compared to bleomycin. Z Naturforsch C, 44, 1063-5.
48 Scifo C, Cardile V, Russo A, et al (2004). Resveratrol and propolis as necrosis or apoptosisinducers in human prostate carcinoma cells. Oncol Res, 14, 415-26.   DOI
49 Shiraishi N, Inai Y, Bi W, Nishikimi M (2005). Fragmentation and dimerization of copper-loaded prion protein by coppercatalysed oxidation. Biochem J, 387, 247-55.   DOI
50 Sinha BK, Trush MA, Kennedt KA, et al (1984). Enzymatic activation and binding of adriamycin to nuclear DNA. Cancer Res, 44, 2892.
51 Skehan P, Storeng R, Scudiero D, et al (1990). New colorimetric cytotoxicity assay for anticancer-drug screening. J Nat Cancer Instit, 82, 1107-12.   DOI
52 Sujoy B, Ramesh MR, Leonard RJ (2009). Role of polyamines in p53-dependent apoptosis of intestinal epithelial cells. Cellular Signalling, 21, 509-22.   DOI
53 Szliszka E, Czuba ZP, Domino M, et al (2009). Ethanolic extract of propolis (EEP) enhances the apoptosis-inducing potential of TRAIL in cancer cells. Molecules, 14, 738-54.   DOI
54 Szliszka E, Czuba ZP, Bronikowska J, et al (2011). Ethanolic extract of propolis augments TRAIL-induced apoptotic death in prostate cancer cells. Evid Based Complement Alternat Med, 2011, 535172
55 Takashi S (2009). Zinc-finger-based artificial transcription factors and their applications. Advanced Drug Delivery Reviews, 43, 8510-615.
56 Youle RJ, Strasser A (2008). The BCL-2 protein family, opposing activities that mediate cell death. Nature Reviews Mol Cell Biol, 9, 47-59.   DOI
57 Taraswi B, Somsubhra N, Susanta R (2009). DNA damage induced p53 down regulates Cdc20 by direct binding to its promoter causing chromatin remodeling. Nucleic Acids Res, 10, 1-11.
58 Teixeira EW, Message D, Negri G, et al (2010). Seasonal variation, chemical composition and antioxidant activity of Brazilian propolis samples. Evid Based Comp Alter Med, 7, 307-15.   DOI
59 Yong YK, Tan JJ, The SS, et al (2013). Clinacanthus nutans extracts are antioxidant with antiproliferative effect on cultured human cancer cell lines. Evid Based Complement Alternat Med, 2013, 462751
60 Zand RS, Jenkins DJ, Diamandis EP (2000). Steroid hormone activity of flavonoids and related compounds. Breast Cancer Res Treat, 62, 35-49.   DOI
61 Valente MJ, Baltazar AF, Henrique R, et al (2011). Biological activities of portuguese propolis, protection against free radical-induced erythrocyte damage and inhibition of human renal cancer cell growth in vitro. Food Chem. Toxicol, 49, 86-92.   DOI
62 Vatansever HS, Sorkun K, Gurhan SID (2010). Propolis from Turkey induces apoptosis through activating caspases inhuman breast carcinoma cell lines. Acta Histochemica, 112, 546-56.   DOI
63 Vogelstein B, Lane D, Levine AJ (2000). Surfing the p53 network. Nature, 408, 307-10.   DOI
64 Yagmurca M, Erdogan H, Iraz M, et al (2004). Caffeic acid phenethyl ester as a protective agent against doxorubicin nephrotoxicity in rats. Clin Chim Acta, 348, 27-34.   DOI
65 Yasuo T, Nobuyuki A, Shinsuke I, et al (2004). Loss of caspase-8 activation pathway is a possible mechanism for CDDP resistance in human laryngeal squamous cell carcinoma HEP-2 cells. International J Oncol, 25, 721-8.