Broad in vitro efficacy of plant-derived betulinic acid against cell lines derived from the most prevalent human cancer types

Kessler, Jan H.; Mullauer, Franziska B.; Roo, Guido M. de; Medema, Jan Paul

doi:10.1016/j.canlet.2006.11.003

Cited by 173 publications

(145 citation statements)

References 38 publications

Supporting

Mentioning

138

Contrasting

Order By: Relevance

“…It was proved to be able to kill melanoma cells via induction of apoptosis [4] . Many other cancer cell lines derived from a variety of different malignancies such as leukemia, prostate, ovarian, breast, lung, and colon cancers were also found to be sensitive to apoptosis induced by BA [5][6][7] . BA did not induce apoptosis in normal cells.…”

Section: Introductionmentioning

confidence: 99%

Effect of betulinic acid on the regulation of Hiwi and cyclin B1 in human gastric adenocarcinoma AGS cells

Yang

Chang

et al. 2009

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim:To investigate the effect of betulinic acid (BA) on the proliferation, apoptosis and cell cycle of gastric adenocarcinoma cell AGS in vitro and elucidate the underlying mechanisms. Methods: The effect of BA on the proliferation of AGS cells was measured by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium (MTT) assay. Apoptosis was analyzed by using Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double-labeled flow cytometry (FCM) and Hoechst 33258 staining. The influence of BA on cell cycle of AGS cells was tested by PI staining. Both FCM and reverse transcription-PCR (RT-PCR) technologies were applied to detect the expression of Hiwi and Cyclin B1. Results: BA exhibited significant cell proliferation inhibition, as well as its potency of inducing apoptosis in AGS cells in vitro in a timeand dose-dependent manner. The IC 50 value for 24 h was 18.25 μg/mL (95% confidence interval: 15.16 to 27.31 μg/mL). Cells treated with BA showed increased cell population in G 2 /M phase, with decreased S phase population. The expression of Hiwi and Cyclin B1 was down-regulated in BA-treated AGS cells in a dose-dependent manner. Conclusion: BA exerted potent effect on growth inhibition, G 2 /M cell cycle arrest and induction of apoptosis in AGS cells in vitro, possibly associated with the down-regulation of Hiwi and its downstream target Cyclin B1 expression. The potent antitumor capacity of BA suggested that it could be a promising new experimental anticancer agent in human gastric adenocarcinoma treatment.

show abstract

Section: Introductionmentioning

confidence: 99%

Effect of betulinic acid on the regulation of Hiwi and cyclin B1 in human gastric adenocarcinoma AGS cells

Yang

Chang

et al. 2009

Acta Pharmacol Sin

View full text Add to dashboard Cite

show abstract

“…However, it is becoming clear that its efficacy extends to many other cancer cell lines derived from a variety of different malignancies such as leukemia, prostate, ovarian, breast, lung, and colon cancer [2][3][4][5][6]. Importantly, BetA-induced apoptosis appears to be independent of p53 [6][7][8], but does show remarkable selectivity for tumor cells over non-transformed cells.…”

Section: Introductionmentioning

confidence: 99%

Betulinic acid induces cytochrome c release and apoptosis in a Bax/Bak-independent, permeability transition pore dependent fashion

2008

Self Cite

View full text Add to dashboard Cite

Betulinic acid (BetA) is a plant-derived pentacyclic triterpenoid that exerts potent anti-cancer effects in vitro and in vivo, but is non toxic to untransformed cells. In our previous study we observed that BetA consistently induced cell death in a broad panel of tumor cell lines. Apoptosis induced by BetA involves activation of caspases, PARP cleavage and DNA fragmentation and was suggested to depend on the mitochondrial pathway. However, conflicting results have been reported with respect to the role of the pro-and anti-apoptotic members of the Bcl-2 family, which are often aberrantly regulated in tumors and thereby confer growth and survival advantages. Here we show that BetA-induced apoptosis critically depends on the release of cytochrome c from the mitochondria and formation of the apoptosome. Nevertheless, over-expression of Bcl-2 or Bcl-XL only provides limited protection against BetAinduced apoptosis. More importantly, Bax/Bak deficient cells are as sensitive to BetA as their wild-type counterparts, suggesting that cytochrome c is released in a nonclassical fashion. In agreement, pre-incubation with cyclosporin A indicated a crucial role for the mitochondrial permeability transition pore (PT) in the induction of apoptosis. Our observations therefore indicate that BetA affects mitochondria and induces cytochrome c release directly via PT Pore. This is only temporarily prevented by anti-apoptotic members of the Bcl-2 family, but independent of Bax and Bak. These findings help to explain the remarkable broad efficacy of BetA against tumor cells of different origin and its effect in tumor cells that are resistant to other chemotherapeutic agents.

show abstract

“…Saponins have been long known as antineoplastic and immunostimulant agents. The discovery of the potent broadspectrum anticancer properties of betulinic acid however have further focused research interest on this class of plant secondary metabolites as possible anticancer lead compounds (1,3,4,7,8,15,16,32,34 A purifi ed mixture containing mostly saponins (PMS) from Astragalus corniculatus Bieb. was used in an in vivo tumor model to demonstrate its protective effect against myeloid Graffi tumour in hamsters, in collaboration with Dr. Reneta Toshkova (BAS).…”

Section: Exploitation Of the Bulgarian Flora's Biodiversity As A Sourmentioning

confidence: 99%

Exploitation of the Bulgarian Flora's Biodiversity as a Source of Immunomodulatory and/or Antineoplastic Agents: Current Challenges and Perspectives

Nikolov

Momekov

Kitanov

et al. 2007

Biotechnology & Biotechnological Equipment

View full text Add to dashboard Cite

Broad in vitro efficacy of plant-derived betulinic acid against cell lines derived from the most prevalent human cancer types

Cited by 173 publications

References 38 publications

Effect of betulinic acid on the regulation of Hiwi and cyclin B1 in human gastric adenocarcinoma AGS cells

Effect of betulinic acid on the regulation of Hiwi and cyclin B1 in human gastric adenocarcinoma AGS cells

Betulinic acid induces cytochrome c release and apoptosis in a Bax/Bak-independent, permeability transition pore dependent fashion

Exploitation of the Bulgarian Flora's Biodiversity as a Source of Immunomodulatory and/or Antineoplastic Agents: Current Challenges and Perspectives

Contact Info

Product

Resources

About