Targeting mitochondrial apoptosis by betulinic acid in human cancers

Drug Discovery Today

Volumn 14, Issue 17-18, 2009, Pages 885-890

  Fulda, Simone ^a   Kroemer, Guido ^b  

^a UNIVERSITY HOSPITAL ULM   (Germany)

^b INSTITUT GUSTAVE ROUSSY   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; ANTIOXIDANT; BETULIC ACID; BEVIRIMAT; DOXORUBICIN; FLUOROURACIL; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; IRINOTECAN; OXALIPLATIN; PLANT MEDICINAL PRODUCT; PROTEIN BCL 2; VINCRISTINE;

ANTIANGIOGENIC ACTIVITY; ANTIINFLAMMATORY ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTIVIRAL ACTIVITY; APOPTOSIS; CANCER CHEMOTHERAPY; CANCER RESISTANCE; CELL FATE; CELL PERMEABILIZATION; CLINICAL TRIAL; COLON CANCER; CYTOTOXICITY; DRUG ABSORPTION; DRUG DISTRIBUTION; DRUG MECHANISM; DRUG POTENCY; DRUG STRUCTURE; DRUG TARGETING; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; LUNG METASTASIS; MALARIA; MALIGNANT NEOPLASTIC DISEASE; MELANOMA; MITOCHONDRIAL MEMBRANE; MITOCHONDRION; NEVUS; NONHUMAN; OVARY CANCER; REGULATORY MECHANISM; REVIEW; SINGLE DRUG DOSE;

ANTINEOPLASTIC AGENTS, PHYTOGENIC; APOPTOSIS; DRUG RESISTANCE, NEOPLASM; HUMANS; MITOCHONDRIAL MEMBRANES; MODELS, BIOLOGICAL; MOLECULAR STRUCTURE; NEOPLASMS; TRITERPENES;

EID: 69749094633     PISSN: 13596446     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.drudis.2009.05.015     Document Type: Review

References (63)

1. Newman D.J., et al. Natural products as sources of new drugs over the period 1981-2002. J. Nat. Prod. 66 (2003) 1022-1037
2. Evan G.I., and Vousden K.H. Proliferation, cell cycle and apoptosis in cancer. Nature 411 (2001) 342-348
3. Hanahan D., and Weinberg R.A. The hallmarks of cancer. Cell 100 (2000) 57-70
4. Galluzzi L., et al. Mitochondria as therapeutic targets for cancer chemotherapy. Oncogene 25 (2006) 4812-4830
5. Paduch R., et al. Terpenes: substances useful in human healthcare. Arch. Immunol. Ther. Exp. 55 (2007) 315-327
6. Liby K.T., et al. Triterpenoids and rexinoids as multifunctional agents for the prevention and treatment of cancer. Nat. Rev. Cancer 7 (2007) 357-369
7. Cichewicz R.H., and Kouzi S.A. Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection. Med. Res. Rev. 24 (2004) 90-114
8. Alakurtti S., et al. Pharmacological properties of the ubiquitous natural product betulin. Eur. J. Pharm. Sci. 29 (2006) 1-13
9. Pisha E., et al. Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis. Nat. Med. 1 (1995) 1046-1051
10. Hengartner M.O. The biochemistry of apoptosis. Nature 407 (2000) 770-776
11. Green D.R., and Kroemer G. The pathophysiology of mitochondrial cell death. Science 305 (2004) 626-629
12. Fulda S., et al. Activation of mitochondria and release of mitochondrial apoptogenic factors by betulinic acid. J. Biol. Chem. 273 (1998) 33942-33948
13. Andre N., et al. Paclitaxel targets mitochondria upstream of caspase activation in intact human neuroblastoma cells. FEBS Lett. 532 (2002) 256-260
14. Fulda S., et al. Molecular ordering of apoptosis induced by anticancer drugs in neuroblastoma cells. Cancer Res. 58 (1998) 4453-4460
15. Fulda S., et al. Betulinic acid triggers CD95 (APO-1/Fas)- and p53-independent apoptosis via activation of caspases in neuroectodermal tumors. Cancer Res. 57 (1997) 4956-4964
16. Wick W., et al. Betulinic acid-induced apoptosis in glioma cells: a sequential requirement for new protein synthesis, formation of reactive oxygen species, and caspase processing. J. Pharmacol. Exp. Ther. 289 (1999) 1306-1312
17. Tan Y., et al. Betulinic acid-induced programmed cell death in human melanoma cells involves mitogen-activated protein kinase activation. Clin. Cancer Res. 9 (2003) 2866-2875
18. Adams J.M., and Cory S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene 26 (2007) 1324-1337
19. Selzer E., et al. Effects of betulinic acid alone and in combination with irradiation in human melanoma cells. J. Invest. Dermatol. 114 (2000) 935-940
20. Selzer E., et al. Betulinic acid-induced Mcl-1 expression in human melanoma - mode of action and functional significance. Mol. Med. 8 (2002) 877-884
21. Thurnher D., et al. Betulinic acid: a new cytotoxic compound against malignant head and neck cancer cells. Head Neck 25 (2003) 732-740
22. Fulda S., and Debatin K.M. Betulinic acid induces apoptosis through a direct effect on mitochondria in neuroectodermal tumors. Med. Pediatr. Oncol. 35 (2000) 616-618
23. Meng R.D., and El-Deiry W.S. p53-independent upregulation of KILLER/DR5 TRAIL receptor expression by glucocorticoids and interferon-gamma. Exp. Cell Res. 262 (2001) 154-169
24. Salti G.I., et al. Betulinic acid reduces ultraviolet-C-induced DNA breakage in congenital melanocytic naeval cells: evidence for a potential role as a chemopreventive agent. Melanoma Res. 11 (2001) 99-104
25. Zuco V., et al. Selective cytotoxicity of betulinic acid on tumor cell lines, but not on normal cells. Cancer Lett. 175 (2002) 17-25
26. Ehrhardt H., et al. Betulinic acid-induced apoptosis in leukemia cells. Leukemia 18 (2004) 1406-1412
27. Rieber M., and Strasberg Rieber M. Induction of p53 without increase in p21WAF1 in betulinic acid-mediated cell death is preferential for human metastatic melanoma. DNA Cell Biol. 17 (1998) 399-406
28. Kasperczyk H., et al. Betulinic acid as new activator of NF-kappaB: molecular mechanisms and implications for cancer therapy. Oncogene 24 (2005) 6945-6956
29. Takada Y., and Aggarwal B.B. Betulinic acid suppresses carcinogen-induced NF-kappa B activation through inhibition of I kappa B alpha kinase and p65 phosphorylation: abrogation of cyclooxygenase-2 and matrix metalloprotease-9. J. Immunol. 171 (2003) 3278-3286
30. Rabi T., et al. Betulinic acid suppresses constitutive and TNFalpha-induced NF-kappaB activation and induces apoptosis in human prostate carcinoma PC-3 cells. Mol. Carcinog. 47 (2008) 964-973
31. Deeb D., et al. CDDO-Me inhibits proliferation, induces apoptosis, down-regulates Akt, mTOR, NF-kappaB and NF-kappaB-regulated antiapoptotic and proangiogenic proteins in TRAMP prostate cancer cells. J. Exp. Ther. Oncol. 7 (2008) 31-39
32. Deeb D., et al. CDDO-me induces apoptosis and inhibits Akt, mTOR and NF-kappaB signaling proteins in prostate cancer cells. Anticancer Res. 27 (2007) 3035-3044
33. Kwon H.J., et al. Betulinic acid inhibits growth factor-induced in vitro angiogenesis via the modulation of mitochondrial function in endothelial cells. Jpn. J. Cancer Res. 93 (2002) 417-425
34. Chintharlapalli S., et al. Betulinic acid inhibits prostate cancer growth through inhibition of specificity protein transcription factors. Cancer Res. 67 (2007) 2816-2823
35. Melzig M.F., and Bormann H. Betulinic acid inhibits aminopeptidase N activity. Planta Med. 64 (1998) 655-657
36. Sjostrom H., et al. Structure and function of aminopeptidase N. Adv. Exp. Med. Biol. 477 (2000) 25-34
37. Mukherjee R., et al. Synthesis of 3-O-acyl/3-benzylidene/3-hydrazone/3-hydrazine/17-carboxyacryloyl ester derivatives of betulinic acid as anti-angiogenic agents. Bioorg. Med. Chem. Lett. 14 (2004) 3169-3172
38. Chowdhury A.R., et al. Betulinic acid, a potent inhibitor of eukaryotic topoisomerase I: identification of the inhibitory step, the major functional group responsible and development of more potent derivatives. Med. Sci. Monit. 8 (2002) BR254-265
39. Syrovets T., et al. Acetyl-boswellic acids are novel catalytic inhibitors of human topoisomerases I and II alpha. Mol. Pharmacol. 58 (2000) 71-81
40. Schmidt M.L., et al. Betulinic acid induces apoptosis in human neuroblastoma cell lines. Eur. J. Cancer 33 (1997) 2007-2010
41. Sarek J., et al. New lupane derived compounds with pro-apoptotic activity in cancer cells: synthesis and structure-activity relationships. J. Med. Chem. 46 (2003) 5402-5415
42. Kim J.Y., et al. Development of C-20 modified betulinic acid derivatives as antitumor agents. Bioorg. Med. Chem. Lett. 11 (2001) 2405-2408
43. You Y.-J., et al. Synthesis and cytotoxic activity of A-ring modified betulinic acid derivatives. Bioorg. Med. Chem. Lett. 13 (2003) 3137-3140
44. Fulda S., et al. Betulinic acid: a new chemotherapeutic agent in the treatment of neuroectodermal tumors. Klin. Padiatr. 211 (1999) 319-322
45. Fulda S., et al. Betulinic acid: a new cytotoxic agent against malignant brain-tumor cells. Int. J. Cancer 82 (1999) 435-441
46. Kessler J.H., et al. Broad in vitro efficacy of plant-derived betulinic acid against cell lines derived from the most prevalent human cancer types. Cancer Lett. 251 (2007) 132-145
47. Fulda S., and Debatin K.-M. Sensitization for anticancer drug-induced apoptosis by betulinic acid. Neoplasia 7 (2005) 162-170
48. Jung G.R., et al. Effect of betulinic acid on anticancer drug-resistant colon cancer cells. Basic Clin. Pharmacol. Toxicol. 101 (2007) 277-285
49. Sawada N., et al. Betulinic acid augments the inhibitory effects of vincristine on growth and lung metastasis of B16F10 melanoma cells in mice. Br. J. Cancer 90 (2004) 1672-1678
50. Eder-Czembirek C., et al. Combination of betulinic acid with cisplatin - different cytotoxic effects in two head and neck cancer cell lines. Oncol. Rep. 14 (2005) 667-671
51. Fulda S., et al. Cooperation of betulinic acid and TRAIL to induce apoptosis in tumor cells. Oncogene 23 (2004) 7611-7620
52. Shin Y.G., et al. Determination of betulinic acid in mouse blood, tumor and tissue homogenates by liquid chromatography-electrospray mass spectrometry. J. Chromatogr. B, Biomed. Sci. Appl. 732 (1999) 331-336
53. Udeani G.O., et al. Pharmacokinetics and tissue distribution of betulinic acid in CD-1 mice. Biopharm. Drug Dispos. 20 (1999) 379-383
54. Smith P.F., et al. Phase I and II study of the safety, virologic effect, and pharmacokinetics/pharmacodynamics of single-dose 3-o-(3′,3′-dimethylsuccinyl)betulinic acid (bevirimat) against human immunodeficiency virus infection. Antimicrob. Agents Chemother. 51 (2007) 3574-3581
55. Martin D.E., et al. Multiple-dose pharmacokinetics and safety of bevirimat, a novel inhibitor of HIV maturation, in healthy volunteers. Clin. Pharmacokinet. 46 (2007) 589-598
56. Yasukawa K., et al. Sterol and triterpene derivatives from plants inhibit the effects of a tumor promoter, and sitosterol and betulinic acid inhibit tumor formation in mouse skin two-stage carcinogenesis. Oncology 48 (1991) 72-76
57. Liby K., et al. Novel semisynthetic analogues of betulinic acid with diverse cytoprotective, antiproliferative, and proapoptotic activities. Mol. Cancer Ther. 6 (2007) 2113-2119
58. Rajendran P., et al. Pharmacological evaluation of C-3 modified betulinic acid derivatives with potent anticancer activity. Invest. New Drugs 26 (2008) 25-34
59. Bi Y., et al. Synthesis and cytotoxic activity of 17-carboxylic acid modified 23-hydroxy betulinic acid ester derivatives. Bioorg. Med. Chem. Lett. 17 (2007) 1475-1478
60. De Clercq E. Current lead natural products for the chemotherapy of human immunodeficiency virus (HIV) infection. Med. Res. Rev. 20 (2000) 323-349
61. Kanamoto T., et al. Anti-human immunodeficiency virus activity of YK-FH312 (a betulinic acid derivative), a novel compound blocking viral maturation. Antimicrob. Agents Chemother. 45 (2001) 1225-1230
62. Aiken C., and Chen C.H. Betulinic acid derivatives as HIV-1 antivirals. Trend Mol. Med. 11 (2005) 31-36
63. Bringmann G., et al. Betulinic acid: isolation from Triphyophyllum peltatum and Ancistrocladus heyneanus, antimalarial activity, and crystal structure of the benzyl ester. Planta Med. 63 (1997) 255-257