Betulin as an antitumor agent tested in vitro on A431, HeLa and MCF7, and as an angiogenic inhibitor in vivo in the CAM assay

Natural Product Communications

Volumn 7, Issue 8, 2012, Pages 981-985

  Dehelean, Cristina Adriana ^a   Feflea, Stefana ^a   Molnár, Judit ^b   Zupko, Istvan ^b   Soica, Codruta ^a  

^a VICTOR BABES UNIVERSITY OF MEDICINE AND PHARMACY   (Romania)

^b UNIVERSITY OF SZEGED   (Hungary)

Author keywords

Antiangiogenic effect; Betulin; Chorioallantoic membrane; Fluorescence staining; MTT assay

Indexed keywords

4 [5 (4 METHYL 1 PIPERAZINYL)[2,5' BI 1H BENZIMIDAZOL] 2' YL]PHENOL; BETULIN; DIMETHYL SULFOXIDE; PROPIDIUM IODIDE;

ANGIOGENESIS; ANIMAL TISSUE; ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; ARTICLE; BARK; BIRCH; BREAST ADENOCARCINOMA; CANCER CELL CULTURE; CAPILLARY PROLIFERATION; CELL ASSAY; CELL FUNCTION; CELL MEMBRANE PERMEABILITY; CELL NUCLEUS; CELL STRUCTURE; CHORIOALLANTOIS; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG CYTOTOXICITY; EMBRYO; ENDOTHELIUM CELL; FLUORESCENCE ANALYSIS; FRAGMENTATION REACTION; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; IN VIVO STUDY; MESENCHYME; NONHUMAN; SQUAMOUS CELL CARCINOMA; UTERINE CERVIX CARCINOMA;

EID: 84865285704     PISSN: 1934578X     EISSN: 15559475     Source Type: Journal    
DOI: 10.1177/1934578x1200700805     Document Type: Article

References (29)

1. Santos RC, Salvador JAR, Marín S, Cascante M. (2009) Novel semisynthetic derivatives of betulin and betulinic acid with cytotoxic activity. Bioorganic & Medicinal Chemistry, 17, 6241-6250.
2. Sagar SM, Yance D, Wong RK. (2006) Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer - Part 1. Current Oncology, 13, 14-26.
3. Fidler IJ. (2001) Regulation of neoplastic angiogenesis. Journal of the National Cancer Institute Monographs, 28, 10-14.
4. Yance DR Jr, Sagar SM. (2006) Targeting angiogenesis with integrative cancer therapies. Integrative Cancer Therapies, 5, 9-29.
5. Fan T-P, Yeh J-C, Leung KW, Yue PYK, Wong RNS. (2006) Angiogenesis: from plants to blood vessels. TRENDS in Pharmacological Sciences, 27, 297-309.
6. Sagar SM, Yance D, Wong RK. (2006) Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer-Part 2. Current Oncology, 13, 99-107.
7. Kerbel RS. (2000) Tumor angiogenesis: past, present and the near future. Carcinogenesis, 21, 505-515.
8. Drag M, Surowiak P, Drag-Zalesinska M, Dietel M, Lage H, Oleksyszyn J. (2009) Comparison of the cytotoxic effects of birch bark extract, betulin and betulinic acid towards human gastric carcinoma and pancreatic carcinoma drug-sensitive and drug-resistant cell lines. Molecules, 14, 1639-1651.
9. Gauthier C, Legault J, Piochon-Gauthier M, Pichette A. (2011) Advances in the synthesis and pharmacological activity of lupane-type triterpenoid saponins. Phytochemisty Reviews, 10, 521-544.
10. Kolomitsyn IV, Holy J, Perkins E, Krasutsky PA. (2007), Analysis and antiproliferative activity of bark extractives of Betula neoalaskana and B. papyrifera. Synthesis of the most active extractive component - betulin 3-caffeate. Natural Product Communications, 2, 17-26.
11. Dehelean C, Feflea S, Ganta S, Amiji M. (2011) Anti-angiogenic effects of betulinic acid administered in nanoemulsion formulation using chorioallantoic membrane assay. Journal of Biomedical Nanotechnology, 7, 317-324.
12. Zuco V, Supino R., Righetti SC, Cleris L, Marchesi E, Gambacorti-Passerini C, Formelli F. (2002) Selective cytotoxicity of betulinic acid on tumor cell lines, but not on normal cells. Cancer Letters, 175, 17-25.
13. Krasutsky PA. (2006) Birch bark research and development. Natural Product Reports, 23, 919-942.
14. Huyke C, Reuter J, Rodig M, Kersten A, Laszczyk M, Scheffler A, Nashan D, Schempp C. (2009) Treatment of actinic keratoses with a novel betulin-based oleogel. A prospective, randomized, comparative pilot study. Journal der Deutschen Dermatologischen Gesellschaft, 7, 128-133.
15. Li Y, He K, Huang Y, Zheng D, Gao C, Cui L, Jin YH. (2010) Betulin induces mitochondrial cytochrome c release associated apoptosis in human cancer cells. Molecular Carcinogenesis, 49, 630-640.
16. Mullauer FB, Kessler JH, Medema JP. (2009) Betulin is a potent antitumor agent that is enhanced by cholesterol. PLoS ONE, 4, e1, doi: 10.1371/journal.pone.0005361.
17. Laszczyk MN. (2009) Pentacyclic triterpenes of the lupane, oleanane and ursane group as tools in cancer therapy. Planta Medica, 75, 1549-1560.
18. Gauthier C, Legault J, Lavoie S, Rondeau S, Tremblay S, Pichette A. (2009) Synthesis and cytotoxicity of bidesmosidic betulin and betulinic acid saponins. Journal of Natural Products, 72, 72-81.
19. Ciurlea SA, Tiulea C, Csanyi E, Berko S, Toma CC, Dehelean CA, Loghin F. (2010) A pharmacotoxicological evaluation of a betulin topical formulation tested on C57BL/6J mouse experimental nevi and skin lesions. Studia Universitatis "Vasile Goldis" Seria Stiintele Vietii, 20, 5-9.
20. Rzeski W, Stepulak A, Szymański M, Juszczak M, Grabarska A, Sifringer M, Kaczor J, Kandefer-Szerszeń M. (2009) Betulin elicits anti-cancer effects in tumour primary cultures and cell lines in vitro. Basic Clinical Pharmacology &. Toxicology, 105, 425-432.
21. Fulda S. (2008) Betulinic acid for cancer treatment and prevention. International Journal of Molecular Sciences, 9, 1096-1107.
22. Demir R, Peros G, Hohenberger W. (2011) Definition of the "drug-angiogenic-activity-index" that allows the quantification of the positive and negative angiogenic active drugs: A study based on the chorioallantoic membrane model. Pathology & Oncology Research, 17, 309-313.
23. Zhao J, Miao J, Zhao B, Zhang S, Yin D. (2005) Safrole oxide inhibits angiogenesis by inducing apoptosis. Vascular Pharmacology, 43, 69-74.
24. Folkman J. (2003) Angiogenesis and apoptosis. Seminars in Cancer Biology, 13, 159-167.
25. Dehelean CA, Soica CM, Toma CC, Feflea S, Gruia AT, Kasa P. (2010) Antitumoral activity of betulin, a compound present in birch tree, in formulations with cyclodextrin. Studia Universitatis "Vasile Goldis" Seria Stiintele Vietii, 20, 55-58.
26. Mosmann T. (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of Immunological Methods, 65, 55-63.
27. Grusch M, Polgar D, Gfatter S, Leuhuber K, Huettenbrenner S, Leisser C, Fuhrmann G, Kassie F, Steinkellner H, Smid K, Peters GJ, Jayaram HN, Klepal W, Szekeres T, Knasmuller S, Krupitza G. (2002) Maintenance of ATP favours apoptosis over necrosis triggered by benzamide riboside. Cell Death & Differentiation, 9, 169-178.
28. Ribatti D. (2010) The chick embryo chorioallantoic membrane as an in vivo assay to study antiangiogenesis. Pharmaceuticals, 3, 482-513.
29. Weidner N, Folkman J, Pozza F, Bevilacqua P, Allred EN, Moore DH, Meli S, Gasparini G. (1992) Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. Journal of the National Cancer Institute, 84, 1875-1887.