Lupane Triterpenoids-Betulin and Betulinic acid derivatives induce apoptosis in tumor cells

Investigational New Drugs

Volumn 29, Issue 2, 2011, Pages 266-272

  Kommera, Harish ^a   Kaluderović, Goran N ^a,b   Kalbitz, Jutta ^c   Paschke, Reinhard ^a  

^a MARTIN LUTHER UNIVERSITY HALLE WITTENBERG   (Germany)

^b UNIVERSITY OF BELGRADE   (Serbia)

^c BioSolutions Halle GmbH   (Germany)

Author keywords

Apoptosis; Betulin; Betulinic acid; Caspase activity; Cytotoxicity; Natural products

Indexed keywords

BETULIC ACID; BETULIN; CASPASE 2; CASPASE 3; CASPASE 8; CASPASE 9; TRITERPENOID; ANTINEOPLASTIC AGENT; CASPASE; LUPANE; TRITERPENE;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL CULTURE; CELL DEATH; CELL SURVIVAL; COLON CANCER; CONTROLLED STUDY; DNA FRAGMENTATION; DOSE RESPONSE; DRUG CYTOTOXICITY; DRUG SELECTIVITY; DRUG STRUCTURE; ENZYME ACTIVITY; ESTERIFICATION; HUMAN; HUMAN CELL; PRIORITY JOURNAL; TUMOR CELL; CHEMISTRY; DRUG EFFECT; DRUG SCREENING; IC 50; KINETICS; METABOLISM; TUMOR CELL LINE;

ANTINEOPLASTIC AGENTS; APOPTOSIS; CASPASES; CELL LINE, TUMOR; CELL SURVIVAL; DNA FRAGMENTATION; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; INHIBITORY CONCENTRATION 50; KINETICS; TRITERPENES;

EID: 79955594006     PISSN: 01676997     EISSN: 15730646     Source Type: Journal    
DOI: 10.1007/s10637-009-9358-x     Document Type: Article

References (21)

1. Fulda S, Jeremias I, Steiner HH, Pietsch T (1999) Debatin KM (1999) Betulinic acid: a new cytotoxic agent against malignant brain-tumor cells. Int J Cancer 82:435-441 (Pubitemid 29302986)
2. Schmidt ML, Kuzmanoff KL, Ling-Indeck L, Pezzuto JM (1997) Betulinic acid induces apoptosis in human neuroblastoma cell lines. Eur J Cancer 33:2007-2010 (Pubitemid 28123444)
3. Zuco V, Supino R, Righetti SC, Cleris K, Marchesi E, Gambacorti- Passerini C, Formelli F (2002) Selective cytotoxicity of betulinic acid on tumor cell lines, but not normal cells. Cancer Lett 175:17-25 (Pubitemid 33153040)
4. Pisha E, Chai H, Lee IS, Chagwedera TE, Farnsworth NR, Cordell AC, Beecher CWW, Fong HHS, Kinghorn AD, Brown DM, Wani MC, Wall ME, Hieken TJ, Das Gupta TK, Pezzuto JM (1995) Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis. Nat Med 1:1046-1051
5. Fulda S, Friesen C, Los M, Scaffidi C, Mier W, Benedict M, Nunez G, Krammer PH, Peter ME, Debatin KM (1997) Betulinic acid triggers CD95 (APO-1/Fas)- and p53-independent apoptosis via activation of caspases in neuroectodermal tumors. Cancer Res 57:4956-4964 (Pubitemid 27469008)
6. Fulda S, Scaffidi C, Susin SA, Krammer PH, Kroemer G, Peter ME, Debatin KM (1998) Activation of mitochondria and release of mitochondrial apoptogenic factors by betulinic acid. J Biol Chem 273:33942-33948 (Pubitemid 29008858)
7. Fulda S, Debatin KM (2000) Betulinic acid induces apoptosis through a direct effect on mitochondria in neuroectodermal tumors. Med Pediatr Oncol 35:616-618
8. Melzig MF, Bormann H (1998) Betulinic acid inhibits aminopeptidase N activity. Planta Med 64:655-657 (Pubitemid 28481482)
9. Kwon HJ, Shim JS, Kim JH, Cho HY Yum YN, Kim SH, Yu J (2002) Betulinic acid inhibits growth factor-induced in vitro angiogenesis via the modulation of mitochondrial function in endothelial cells. Jpn J Cancer Res 93:417-425 (Pubitemid 34506252)
10. Salti GI, Kichina JV, Das Gupta TK, Uddin S, Bratescu L, Pezzuto JM, Mehta RG, Constantinou AI (2001) Betulinic acid reduces ultraviolet-C-induced DNA breakage in congenital melanocyte naeval cells:Evidence for a potential role as a chemopreventive agent. Melanoma Res 11:99-104 (Pubitemid 32385812)
11. Syrovets T, Buchele B, Gedig E, Slupsky JR, Simmet T (2000) Acetyl-boswellic acids are novel catalytic inhibitors of human topoisomerase I and IIa. Mol Pharm 58:71-81 (Pubitemid 30452529)
12. Yasukawa K, Takido M, Matsumoto T, Takeuchi M, Nakagawa S (1991) Sterol and triterpene derivatives from plants inhibit the effects of a tumor promoter, and sitosterol and betulinic acid inhibit tumor promotion in mouse skin two-stage carcinogenesis. Oncology 48:72-76
13. Yasukawa K, Yu SY, Yamanouchi S, Takido M, Akihisa T, Tamura T (1995) Some lupane-type triterpenes inhibit tumor promotion by 12-O- tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin. Phytomedicine 4:309-313
14. Bringmann G, Saeb W, Assi LA, Francois G, Narayanan ASS, Peters K, Peters EM (1997) Betulinic acid: Isolation from Triphyophyllum peltatum and Ancistrocladus heyneanus, antimalarial acitivity, and crystal structure of the benzyl ester. Planta Med 63:255-257 (Pubitemid 27287071)
15. Steele JCP, Warhurst DC, Kirby GC, Simmonds MSJ (1999) In vitro and in vivo evaluation of betulinic acid as an antimalarial. Phytother Res 13:115-119 (Pubitemid 29129443)
16. Recio MC, Giner RM, Manez S, Gueho J, Julien HR, Hostettmann K, Rios JL (1995) Investigations on the steroidal anti-inflammatory activity of triterpenoids from Diospyros leucomelas. Planta Med 61:9-12
17. Huguet A-I, Recio MC, Manez S, Giner RM, Rios JL (2000) Effect of triterpenoids on the inflammation induced by protein kinaseCactivators, neuronally acting irritants and other agents. Eur J Pharmacol 410:69-81 (Pubitemid 32008132)
18. Fujioka T, Kashiwada Y, Kilkuskie RE, Cosentino LM, Ballas LM, Jiang JB, Janzen WP, Chen I-S, Lee KH (1994) Anti-AIDS agents.11Betulinic acid and platanic acid as anti-HIV principles from Syzigium claviflorum, and the anti-HIV activity of structurally related triterpenes. J Nat Prod 57:243-247
19. Kommera H, Kaluderović GN, Kalbitz J, Paschke R (2009) Microwave mediated synthesis and structure-activity relationships of betulin and betulinic acid derivatives. Bioorg Med Chem submitted
20. Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D, Warren JT, Bokesch H, Kenney S, Boyd MR (1990) New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst 82(13):1107-1112 (Pubitemid 20213250)
21. Dietrich A, Mueller T, Paschke R, Kalinowski B, Behlendorf T, Reipsch F, Fruehauf A, Schmoll HJ, Kloft C, Voigt W (2008) 2-(4-(tetrahydro-2H-pyran-2- yloxy)-undecyl)-propane-1, 3- diamminedichloroplatinum(II): A Novel Platinum Compound that Overcomes Cisplatin Resistance and Induces Apoptosis by Mechanisms Different from that of Cisplatin. J Med Chem 51:5413-5422