Anti Tumoral Properties of Punica Granatum (Pomegranate) Peel Extract on Different Human Cancer Cells

  • Modaeinama, Sina (Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Urmia University) ;
  • Abasi, Mozhgan (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences) ;
  • Abbasi, Mehran Mesgari (Research Committee, Tabriz University of Medical Sciences) ;
  • Jahanban-Esfahlan, Rana (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences)
  • Published : 2015.09.02


Background: Medicinal plants, especially examples rich in polyphenolic compounds, have been suggested to be chemopreventive on account of antioxidative properties. Punica granatum (PG) (pomegranate) is a well known fruit in this context, but its cytotoxicity in cancer cells has not been extensively studied. Here, we investigated the antiproliferative properties of a peel extract of PG from Iran in different human cancer cells. Materials and Methods: A methanolic extract of pomegranate peel (PPE) was prepared. Total phenolic content(TPC) and total flavonoid conetnt (TFC) were determined by colorimetric assays. Antioxidant activity was determined by DPPH radical scavenging activity. The cytotoxicity of different doses of PPE (0, 5, 20, 100, 250, 500, $1000{\mu}g/ml$) was evaluated by MTT assays with A549 (lung non small cell cancer), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer), and PC-3 (prostate adenocarcinoma) cells. Results: Significant (P<0.01) or very significant (P<0.0001) differences were observed in comparison with negative controls at all tested doses (5-$1000{\mu}g/ml$). In all studied cancer cells, PPE reduced the cell viability to values below 40%, even at the lowest doses. In all cases, IC50 was determined at doses below $5{\mu}g/ml$. In this regard, MCF-7 breast adenocarcinoma cells were the most responsive cells to antiprolifreative effects of PPE with a maximum mean growth inhibition of 81.0% vs. 69.4%, 79.3% and 77.5% in SKOV3, PC-3 and A549 cells, respectively. Conclusions: Low doses of PPE exert potent anti-proliferative effects in different human cancer cells and it seems that MCF-7 breast adenocarcinoma cells are the most cells and SKOV3 ovarian cancer cells the least responsive in this regard. However, the mechanisms of action need to be addressed.



  1. Abbasi MM, Khiavi MM, Monfaredan A, et al (2014a). DOXMTX-NPs augment p53 mRNA expression in OSCC model in rat: effects of IV and oral routes. Asian Pac J Cancer Prev, 15, 8377-82.
  2. Abbasi MM, Monfaredan A, Hamishehkar H, et al (2014b). New formulated "DOX-MTX-loaded nanoparticles" downregulate HER2 gene expression and improve the clinical outcome in OSCCs model in rat: the effect of IV and oral modalities. Asian Pac J Cancer Prev, 15, 9355-60.
  3. Abbasi MM, Monfaredan A, Hamishehkar H, et al (2014c). Novel DOX-MTX nanoparticles improve oral SCC clinical outcome by down regulation of lymph dissemination factor VEGF-C expression in vivo: oral and IV modalities. Asian Pac J Cancer Prev, 15, 6227-32.
  4. Balunas MJ, Su B, Brueggemeier RW, et al (2008). Natural products as aromatase inhibitors. Anticancer Agents Med Chem, 8, 646-82.
  5. Brand-Williams W, Cuvelier M, Berset C (1995). Use of a free radical method to evaluate antioxidant activity. LWT-Food Science Technol, 28, 25-30.
  6. Elango S, Balwas R, Vijaya Padma V (2011). Gallic acid isolated from pomegranate peel extract induces reactive oxygen species mediated apoptosis in A549 cell line. J Cancer Therapy, 2, 638-45.
  7. Jahanban- Esfahlan A, Jahanban- Esfahlan R, jamei R, et al (2012). Morphology and physicochemical properties of 40 genotypes of almond (Amygdalus communisL.) fruits. Eur J Experimental Biol, 2, 2456-64
  8. Jahanban- Esfahlan A, Jamei R, Jahanban-Esfahlan R (2010). The importance of almond (Prunus amygdalusL.) and its by-products. Food Chem, 120, 349-60.
  9. Jahanban Esfahlan R, Zarghami N, Rahmati-Yamchi M, et al (2011). Quantification of steroid receptors gene expression in breast cancer patients: possible correlation with serum level of adipocytokines. J Cancer Therapy, 2, 659-65.
  10. Lansky EP, Newman RA (2007). Punica granatum(pomegranate) and its potential for prevention and treatment of inflammation and cancer. J Ethnopharmacol, 109, 177-206.
  11. Shafie SM, Liotta LA (1980). Formation of metastasis by human breast carcinoma cells (MCF-7) in nude mice. Cancer Letters, 11, 81-7.
  12. Sineh Sepehr K, Baradaran B, Mazandarani M, et al (2012). Studies on the cytotoxic activities of punica granatum l. var. spinosa (apple punice) extract on prostate cell line by induction of apoptosis. ISRN Pharm, 2012, 547942.
  13. Singh RP, Chidambara Murthy KN, GK J (2002). Studies on the antioxidant activity of pomegranate (Punica granatum) peel and seed extracts using in vitro models. J Agric Food Chem, 50, 81-6.
  14. Singleton V, Rossi JA (1965). Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents. Am J Enol Viticult, 16, 144-58.
  15. Syed DN, Afaq F, Mukhtar H (2007). Pomegranate derived products for cancer chemoprevention. Semin Cancer Biol, 17, 377-85.
  16. Valiyari S, Jahanban-Esfahlan R, Zare Shahneh F, et al (2013). Cytotoxic and apoptotic activity of scrophularia oxysepala in MCF-7 human breast cancer cells. Toxicol Environ Chem, 95, 1208-20.
  17. Zhishen J, Mengcheng T, Jianming W (1999). The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals. Food Chemistry, 64, 555-9.

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