Vaccinium Vitis-Idaea L., Origin from Bulgaria Indicate in Vitro Antitumor Еffect on Human Cervical and Breast Cancer Cells

  • Svetla G. Angelova Department of Virology, National Centre of Infectious and Parasitic Diseases (NCIPD), 44A Stoletov Blvd, 1233 Sofia, Bulgaria
  • Stefka Kr. Ivanova Department of Virology, National Centre of Infectious and Parasitic Diseases (NCIPD), 44A Stoletov Blvd, 1233 Sofia, Bulgaria
  • Ivelina Trifonova Department of Virology, National Centre of Infectious and Parasitic Diseases (NCIPD), 44A Stoletov Blvd, 1233 Sofia, Bulgaria
  • Silviya Voleva Department of Virology, National Centre of Infectious and Parasitic Diseases (NCIPD), 44A Stoletov Blvd, 1233 Sofia, Bulgaria
  • Irina Georgieva Department of Virology, National Centre of Infectious and Parasitic Diseases (NCIPD), 44A Stoletov Blvd, 1233 Sofia, Bulgaria
  • Asya Stoyanova Department of Virology, National Centre of Infectious and Parasitic Diseases (NCIPD), 44A Stoletov Blvd, 1233 Sofia, Bulgaria
  • Ivayla Dincheva AgroBioInstitute, Plant Genetic Research Group, 8 Dr.Tsankov Blvd, 1000 Sofia, Bulgaria
Keywords: Vaccinium vitis-idaea L, antitumor activity, HeLa, MCF7.

Abstract

Cancer is a socially significant disease. Along with efforts to understand the complex genetic/epigenetic factors that trigger a carcinogenesis, it is also necessary to analyze the potential natural active substances that may delay or even stop neoplastic transformation. Promising candidates are Bulgarian cranberries from high mountain plant populations, which are rich in phenolics and anthocyanins and have proven beneficial effects on human body.The present study aims to evaluate in vitro, antitumor activities of total extracts and purified nonanthocyanin and anthocyanins fractions of Vaccinium vitis-idaea L., picked in Bulgaria on human cervical (HeLa) and breast (MCF7) cancer cell lines, as well as to examine some of the apoptotic mechanisms underlying them.Materials and methods: Four methanol extracts and respective number of purified B- nonanthocyanin / C- anthocyanins fractions of Bulgarian lingonberry were used. Antitumor effect was established by Trypan Blue method, monitoring of morphological changes and МТТ cell viability assay. Assessment of apoptotic activity was performed using DNA fragmentation method.Results: The results from МТТ analyses showed that B- nonanthocyanin fractions of Bulgarian lingonberry have well expressed inhibitory effect on survival of tested tumor cells. The observed effect dependent of the dose administered and were stronger in relation with the high-mountain populations and HeLa cell line. The integrity of the extracted DNA from treated survival cells indicates possible apoptosis mechanisms under the action of biologically active ingredients from lingonberries.Conclusion: Survey of antitumor activities of Bulgarian lingonberries based on molecular methods, could contribute to establish the natural substances useful for human health in general and practical oncology.

References

. Shoeb M. (2006). “Anticancer agents from medicinal plants”. Bangladesh J Pharmacol ., 1, pp 35-41.

. 2 Nikolov S., Momekov G., Kitanov G., et al., (2007). “Exploitation of the Bulgarian flora’s biodiversity as a source of immunomodulatory and/or antineoplastic agents: current challenges and perspectives”. Biotechnol & Biotechnol Equipment, 21(4), pp 471-477.

. 3 Singh I., Gautam L.K., Kaur I.R. (2016). “Effect of oral cranberry extract (standardized proanthocyanidin-A) in patients with recurrent UTI by pathogenic E. coli: a randomized placebo-controlled clinical research study”. Int Urol Nephrol., 48(9), pp 1379-86

. 4 Jepson R.G.,Williams G.; Craig J.C. (2012). “Cranberries for preventing urinary tract infections“. Cochrane Database Syst. Rev., 10, CD001321.

. 5 Puupponen-Pimia R., Nohynek L., Alakomi H., Oksman-Caldentey K. (2005). “Bioactive berry compounds – novel tools against human pathogens”. Applied Microbiology and Biotechnology, 67, pp 8-18.

. 6 Battino M., Beekwilder J., Denoyes-Rothan B., Laimer M., McDougall G.J., Mezzetti B. (2009). “Bioactive compounds in berries relevant to human health”. Nutr Rev., 67, S145-50. doi: 10.1111/j.1753-4887.2009.00178.x.

. [7] Hossain M.M., Banik N.L., Ray S.K. (2012). “Synergistic anti-cancer mechanisms of curcumin and paclitaxel for growth inhibition of human brain tumor stem cells and LN18 and U138MG cells”. Neuro Int., 61(7), pp 1102-13.

. 8 Etienne-Selloum N., Dandache I., Sharif T., Auger C., Schini-Kerth V.B. (2013). „Polyphenolic compounds targeting p53-family tumor suppressors: Current progress and challenges. In Future aspects of tumor suppressor gene“. IntechOpen.

. 9 Nikolaeva-Glomb L., Mukova L., Nikolova N., Badjakov I., Dincheva I., Kondakova V., Doumanova L., Galabov A.S. (2014). “In vitro antiviral activity of a series of wild berry fruit extracts against representatives of Picorna-, Orthomyxo- and Paramyxoviridae”. Nat Prod Commun., 9(1), pp 51-4.

. 10 Dincheva I., Badjakov I., Angelova S., Georgieva I., Genova-Kalu5 P., Stoyanova A., Nikolaeva-Glomb L., Nestby R., Kondakova V. (2017). „In vitro antitumor activity of proanthocyanidin-rich fractions from vaccinium berries originating from Bulgaria and Norway“. 3rd International Conference on Natural Products Utilization, 18.10.-21.10.2017, Bansko, Bulgaria, рр 61.

. 11 Newman D.J., Cragg G.M. (2012). „Natural products as sources of new drugs over the 30 years from 1981 to 2010“. J Nat Prod., 75(3), 311-35.

. 12 Es-Safi N. (2012). „Plant Polyphenols: Extraction, Structural Characterization, Hemisynthesis and Antioxidant Properties. In: Rao DV, editor. Phytochemicals as Nutraceuticals - Global Approaches to Their Role in Nutrition and Health“. INTECH, pp. 181-206.

. 13 Quideau S., Deffieux D., Douat-Casassus C., Pouysegu L. (2011). „Plant polyphenols: chemical properties, biological activities, and synthesis“. Angewandte Chemie, 50(3, 586-621.

. 14 Prior R., Cao G., Martin A., Sofic E., McEwen J., O'Brien C., Lischner N., Ehlenfeldt M., Kalt W., Krewer G., Mainland C. (1998). „Antioxidant capacity as influenced by total phenolic and anthocyanin content, maturity, and variety of Vaccinium species“. Journal of agricultural and food chemistry, 46, 2686-2693.

. 15 Dincheva I., Badjakov I. (2016). „Assesment of the Anthocyanin Variation in Bulgarian Bilberry (Vaccinium Myrtillus L.) and Lingonberry (Vaccinium Vitis-Idaea L.)“. IJMPS, 6(3), 39-50.

. 16 Heinonen M. (2007). „Antioxidant activity and antimicrobial effect of berry phenolics - a Finnish perspective“. Molecular Nutrition & Food Research, 51 (6), 684-691.

. 17 Masoudi M., and Saiedi M. (2017). „Anti-carcinoma activity of Vaccinium oxycoccos“. Pharm. Lett., 9, 74–79.

. 18 Seeram N.P., Adams L.S., Zhang Y., Lee R., Sand D., Scheuller H.S., Heber D. (2006). „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., 54, 9329–9339.

. 19 Kizhakkayil J., Thayyullathil F., Chathoth S., Hago A., Patel M., Galadari S. (2010). „Modulation of curcumin-induced Akt phosphorylation and apoptosis by PI3K inhibitor in MCF-7 cells“. Biochem Biophys Res Commun., 394(3), 476-81.

. 20 Jurikova T., Skrovankova S., Mlcek J., Balla S., Snopek L. (2019). „Bioactive compounds, antioxidant activity, and biological effects of european cranberry (vaccinium oxycoccos)“. Molecules, 24(1), 24.

. 21 He X., Liu R.H. (2006). “Cranberry phytochemicals: isolation, structure elucidation and their antiproliferative and antioxidant activities”. J Agric Food Chem., 54, pp 7069–7074.

. 22 Kondo M. (2006). “Phytochemical studies of extracts from cranberry (Vaccinium macrocarpon) with anti-cancer, anti-fungal and cardioprotective properties”. M.S. Thesis, University of Massachusetts Dartmouth.

. 23 Neto C.C. (2007). “Cranberry and its phytochemicals: a review of in vitro anticancer studies”. J Nutr., 137, pp 186S 193S.

. 24 Dhandapani K.M., Mahesh V.B., Brann D.W. (2007). „Curcumin suppresses growth and chemoresistance of human glioblastoma cells via AP-1 and NFkappaB transcription factors“. J Neurochem, 102(2), 522-38.

. 25 Walter A., Etienne-Selloum N., Brasse D., Khallouf H., Bronner C., Rio M.C. (2010). „Intake of grape-derived polyphenols reduces C26 tumor growth by inhibiting angiogenesis and inducing apoptosis“. FASEB journal, 24(9), 3360-9.

. 26 Singh N., Zaidi D., Shyam H., Sharma R., Balapure A.K. (2012). „Polyphenols sensitization potentiates susceptibility of MCF-7 and MDA MB-231 cells to Centchroman“. PloS one., 7(6), e37736.

. 27 Arden N., Betenbaugh M.J. (2004). „Life and death in mammalian cell culture: strategies for apoptosis inhibition“. Trends Biotechnol., 22(4),174-180.

. 28 Johnson V.L., Ko S.C., Holmstrom T.H., Eriksson J.E., Chow S.C. (2000). „Effector caspases are dispensable for the early nuclear morphological changes during chemical-induced apoptosis“. J Cell Sci., 113(Pt 17):2941-53.

Published
2019-06-09
Issue
Vol 56 No 1 (2019)
Section
Articles

Authors who submit papers with this journal agree to the following terms:

  1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
  2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
  3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
  4. By submitting the processing fee, it is understood that the author has agreed to our terms and conditions which may change from time to time without any notice.
  5. It should be clear for authors that the Editor In Chief is responsible for the final decision about the submitted papers; have the right to accept\reject any paper.  The Editor In Chief will choose any option from the following to review the submitted papers:A. send the paper to two reviewers, if the results were negative by one reviewer and positive by the other one; then the editor may send the paper for third reviewer or he take immediately the final decision by accepting\rejecting the paper. The Editor In Chief will ask the selected reviewers to present the results within 7 working days, if they were unable to complete the review within the agreed period then the editor have the right to resend the papers for new reviewers using the same procedure. If the Editor In Chief was not able to find suitable reviewers for certain papers then he have the right to accept\reject the paper.B. sends the paper to a selected editorial board member(s). C. the Editor In Chief himself evaluates the paper.
  6. Author will take the responsibility what so ever if any copyright infringement or any other violation of any law is done by publishing the research work by the author
  7. Before publishing, author must check whether this journal is accepted by his employer, or any authority he intends to submit his research work. we will not be responsible in this matter.
  8. If at any time, due to any legal reason, if the journal stops accepting manuscripts or could not publish already accepted manuscripts, we will have the right to cancel all or any one of the manuscripts without any compensation or returning back any kind of processing cost.
  9. The cost covered in the publication fees is only for online publication of a single manuscript.