In vitro investigation of anti-cancer activity of propolis on hepatocellular carcinoma cells

The aim of the current study is to investigate the anti-cancer activity of propolis on liver cancer, with a mechanistic approach. Ethanol extract of the collected propolis was prepared using maceration technique and anti-cancer activity of the extract was investigated on liver hepatocellular carcinoma cells (HepG2 and Hep3B cells) by focusing on viability, intracellular ROS level, total antioxidant status and apoptosis through caspase-3 activity. Total flavonoid content, total phenolic content and ferric reducing antioxidant potential values of the propolis were determined as 505.12±10.08 (mg QE/g), 308.72±5.33 (mg GAE/g) and 247.64±7.27 (mg Tro/g), respectively. Ethanol extract of the propolis induced statistically significant (p < 0.01) decreases in viability of hepatocellular carcinoma cells, HepG2 and Hep3B cells, as evidenced by IC50 values (e.g. IC 50 values of 72 h treated HepG2 and Hep3B cells were 25.62±1.50 and 31.74±2.72 μg/mL, respectively). These powerful cytotoxic effects are caused by statistically significant (p < 0.01) decrease in intracellular ROS level by natural antioxidants such as flavonoids and phenolic acids, as well as statistically significant (p < 0.01) increase in apoptosis induced by caspase-3 activity. These results suggest the great potential of propolis as a potent anti-tumor compound in liver cancer treatment for further researches.

___

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394-424.

2. Liu C, Chen K, Chen P. Treatment of liver cancer. Cold Spring Harb Perspect Med. 2015;5:a021535.

3. Sorkun K, Suer B, Salih B. Determination of chemical composition of Turkish propolis. Z Naturforsch. 2001;56:666-8.

4. Vatansever SH, Sorkun K, Gurhan SID, et al. Propolis from Turkey induces apoptosis through activating caspases in human breast carcinoma cell lines. Acta Histochem. 2010;112:546-56.

5. Farooqui T, Farooqui AA. Molecular mechanism underlying the therapeutic activities of propolis: A critical review. Curr Nutr Food Sci. 2010;6:186-99.

6. Turan I, Demir S, Misir S, et al. Cytotoxic effect of Turkish Propolis on liver, colon, breast, cervix and prostate cancer cell lines. Trop J Pharm Res. 2015;14:777-82.

7. Kubiliene L, Laugaliene V, Pavilonis A, et al. Alternative preparation of propolis extracts: comparison of their composition and biological activities. BMC Complement Altern Med. 2015;15:156.

8. Gunduz C, Biray C, Kosova B, et al. Evaluation of Manisa propolis effect on leukemia cell line by telomerase activity. Leuk Res. 2005;29:1343-46.

9. Llovet JM, Zucman-Rossi J, Pikarsky E, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2016;2:16018.

10. Ahn MR, Kumazawa S, Usui Y, et al. Antioxidant activity and constituents of propolis collected in various areas of China. Food Chem. 2007;101:1383-92.

11. Singleton VL, Rossi JR. Colorimetry of total phenols with phosphomolybdic-phosphotungstic acid reagents. Am J Enol Vitic. 1965;16:144-58.

12. Mohammadzadeh S, Sharriatpanahi M, Hamedi M, et al. Antioxidant power of Iranian propolisextract. Food Chem. 2007;103:729-33.

13. Aranda A, Sequedo L, Tolosa L, et al. Dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay: a quantitative method for oxidative stress assessment of nanoparticle-treated cells. Toxicol In Vitro. 2013;27:954-63.

14. Orangi M, Pasdaran A, Shanehbandi D, et al. Cytotoxic and apoptotic activities of methanolic subfractions of Scrophularia oxysepala against human breast cancer cell line. Evid Based Complement Alternat Med. 2016;2016:8540640.

15. Ucar M, Deger O, Gerigelmez AY, et al. Effect of Turkish pollen and propolis extracts on caspase-3 activity in myeloid cancer cell lines. Trop J Pharm Res. 2016;15:2445-49.

16. Kumazawa S, Hamasaka T, Nakayama T. Antioxidant activity of propolis of various geographic origins. Food Chem. 2004;84:329-39.

17. Ozdal T, Sari-Kaplan G, Mutlu-Altundag E, et al. Evaluation of Turkish propolis for its chemical composition, antioxidant capacity, anti-proliferative effect on several human breast cancer cell lines and proliferative effect on fibroblasts and mouse mesenchymal stem cell line. J Apic Res. 2018;57:1-12.

18. Misir S, Aliyazicioglu Y, Demir S, et al. Antioxidant properties and protective effect of Turkish propolis on t-BHP-induced oxidative stress in foreskin fibroblast cells. Indian J Pharm Educ. 2018;52:94-100.

19. Kalaycıoğlu Z, Kaygusuz H, Döker S, et al. Characterization of Turkish honeybee pollens by principal component analysis based on their individual organic acids, sugars, minerals, and antioxidant activities. LWT-Food Sci Technol. 2017;84:402-8.

20. Freire KRL, Lins ACS, Dórea MC, et al. Palynological origin, phenolic content, and antioxidant properties of honeybee collected pollen from Bahia, Brazil. Molecules. 2012;17:1652-64.

21. Negri G, Teixeira EW, Alves ML, et al. Hydroxycinnamic acid amide derivatives, phenolic compounds and antioxidant activities of extracts of pollen samples from Southeast Brazil. J Agric Food Chem. 2011;59:5516-22.

22. Kocot J, Kiełczykowska M, Luchowska-Kocot D, et al. Antioxidant potential of propolis, bee pollen, and royal jelly: Possible medical application. Oxid Med Cell Longev. 2018;2018:7074209.

23. Qiu GH, Xie X, Xu F, et al. Distinctive pharmacological differences between liver cancer cell lines HepG2 and Hep3B. Cytotechnology. 2015;67:1-12.

24. Murakami Y, Hayashi K, Hirohashi S, et al. Aberrations of the tumor suppressor p53 and retinoblastoma genes in human hepatocellular carcinomas. Cancer Res. 1991;51:5520-5.

25. Chi TY, Chen GG, Lai PB. Eicosapentaenoic acid induces Fas-mediated apoptosis through a p53-dependent pathway in hepatoma cells. Cancer J. 2004;10:190-200.

26. Choi E, Kim G. Antioxidant and anticancer activity of Artemisia princeps var. orientalis extract in HepG2 and Hep3B hepatocellular carcinoma cells. Chin J Cancer Res. 2013;25:536-43.

27. Žižić JB, Vuković NL, Jadranin MB, et al. Chemical composition, cytotoxic and antioxidative activities of ethanolic extracts of propolis on HCT-116 cell line. J Sci Food Agric. 2013;93:3001-9.

28. Sainz RM, Lombo F, Mayo JC. Radical decisions in cancer: redox control of cell growth and death. Cancers (Basel). 2012;4:442-74.

29. Feitelson MA, Arzumanyan A, Kulathinal RJ, et al. Sustained proliferation in cancer: Mechanisms and novel therapeutic targets. Semin Cancer Biol. 2015;35:S25-54.

30. Liu J, Wang Z. Increased oxidative stress as a selective anticancer therapy. Oxid Med Cell Longev. 2015;2015:294303.

31. Kaushik N, Uddin N, Sim GB, et al. Responses of solid tumor cells in DMEM to reactive oxygen species generated by non-thermal plasma and chemically induced ROS systems. Sci Rep. 2015;5:8587.

32. Cohen GM. Caspases: The executioners of apoptosis. Biochem J. 1997;326:1-16.

33. Janicke RU, Sprengart ML, Wati MR, et al. Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J Biol Chem. 1998;273:9357-60.

34. Eom HS, Lee EJ, Yoon BS, et al. Propolis inhibits the proliferation of human leukaemia HL-60 cells by inducing apoptosis through the mitochondrial pathway. Nat Prod Res. 2010;24:375-86.

35. Watkins R, Wu L, Zhang C, et al. Natural product-based nanomedicine: recent advances and issues. Int J Nanomedicine. 2015;10:6055-74.

36. Bilia AR, Piazzini V, Guccione C, et al. Improving on nature: The role of nanomedicine in the development of clinical natural drugs. Planta Med. 2017;83(5):366-81.

37. Bilia AR, Piazzini V, Risaliti L, et al. Nanocarriers: A successful tool to increase solubility, stability and optimise bioefficacy of natural constituents. Curr Med Chem. 2018;[Epub ahead of print]

38. Gokduman K, Demir AS. Camptothecin anticancer drug loaded iron oxide micro and nanoparticles: Tuning targeted and sustained release of the drug in bioactive form. Curr Nanosci. 2013;9:704-10.

39. Gokduman K. Strategies targeting DNA topoisomerase I in cancer chemotherapy: Camptothecins, nanocarriers for camptothecins, organic non-camptothecin compounds and metal complexes. Curr Drug Targets. 2016;17:1928-39.

40. Gokduman K, Bestepe F, Li L, et al. Dose-, treatment- and time-dependent toxicity of superparamagnetic iron oxide nanoparticles on primary rat hepatocytes. Nanomedicine. 2018;13:1267-84.
Medicine Science-Cover
  • ISSN: 2147-0634
  • Yayın Aralığı: Yılda 4 Sayı
  • Başlangıç: 2012
  • Yayıncı: Effect Publishing Agency ( EPA )
Sayıdaki Diğer Makaleler

Relationship of chronic / recurrent acute tonsillitis and the family medical history in children: A cross-sectional study

Ahmet Hamdi KEPEKCİ, Kadir DASTAN

Milk expression and maternity leave as determinants of breastfeeding among mothers employed in a baby friendly hospital

Meltem GUNES, Mualla AYKUT, Neslihan ONER, Arda BORLU

Diffusion weighted magnetic resonance imaging in differentiation of small focal liver lesions (≤ 10 mm) detected in patients with extrahepatic primary malignancy

Ahmet SOYUCOK, Kerim ASLAN, Murat DANACI, Ilkay CAMLİDAG

Effects of preoperative oral carbohydrate solution intake on Patients’ anxiety

Cihan DOGER, Zehra Esin GENCER, Ozgur CANOLER, Gulcin OZALP, Gonca OGUZ, Mensure KAYA, Nihal KADİOGULLARI

In vitro investigation of anti-cancer activity of propolis on hepatocellular carcinoma cells

Kurtulus GOKDUMAN

Relationship between traumatic orthopedic injuries and attention deficit hyperactivity disorder symptoms in children

Ali KARAYAGMURLU, Cem GOKCEN, Mustafa İSİK, Ugur PAMUKCU, Onur Burak DURSUN

Safety of midazolam-propofol combination for sedation in pediatric patients undergoing gastrointestinal endoscopy

Sami EKSERT, Mehmet Emin INCE, Necati BALAMTEKİN, Mustafa GULGUN

Assessment of pituitary function in patients with nasopharyngeal carcinoma: The effect of radiotherapy

Ozlem Ozkaya AKAGUNDUZ, Banu Sarer YUREKLİ, Ilgin Yildirim SİMSİR, Mustafa ESASSOLAK

Postural stability and the relationship with enthesitis in ankylosing spondylitis:A cross-sectional study

Sena TOLU, Nurbanu HİNDİOGLU, İbrahim Ethem KİRAZ, Merve Calkin KORKMAZ

Skin, hair and nail findings in children with beta-thalassemia

Emine Tugba ALATAS, Suzan Demir PEKTAS, Gursoy DOGAN, Mehmet Fatih AZİK