Effects of betulinic acid on proliferation and apoptosis in Jurkat cells and its in vitro mechanism

Chen, Zi; Wu, Qirui; Yan, Chen; He, Jing

doi:10.1007/s11596-008-0604-9

Cited by 14 publications

(6 citation statements)

References 18 publications

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“…Cyclin D3 was found to be sharply decreased in Jurkat cells treated with BetA and the same study also found that BetA regulates the cell cycle through the induction of G 0 /G 1 arrest, thereby inhibiting proliferation [106]. Another group found accumulation of p21 on BetA exposure in glioma cells.…”

Section: Cell Cyclementioning

confidence: 72%

Betulinic acid, a natural compound with potent anticancer effects

Mullauer

Kessler²,

Medema³

2010

Anti-Cancer Drugs

178

105

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New therapies using novel mechanisms to induce tumor cell death are needed with plants playing a crucial role as a source for potential anticancer compounds. One highly promising class of natural compounds are the triterpenoids with betulinic acid (BetA) as the most prominent representative. In-vitro studies have identified this agent as potently effective against a wide variety of cancer cells, also those derived from therapy-resistant and refractory tumors, whereas it has been found to be relatively nontoxic for healthy cells. In-vivo preclinically applied BetA showed some remarkable anticancer effects and a complete absence of systemic toxicity in rodents. BetA also cooperated with other therapies to induce tumor cell death and several potent derivatives have been discovered. Its antitumor activity has been related to its direct effects on mitochondria where it induces Bax/Bak-independent cytochrome-c release.

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Section: Cell Cyclementioning

confidence: 72%

Betulinic acid, a natural compound with potent anticancer effects

Mullauer

Kessler²,

Medema³

2010

Anti-Cancer Drugs

178

105

View full text Add to dashboard Cite

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“…BA also down regulates the expression of STAT3-regulated gene products such as Bcl-xL, Bcl-2, cyclin D1 and survivin, which correlates with an increase in apoptosis as indicated by an increase in the sub-G1 cell population and an increase in caspase-3-induced PARP cleavage [12]. The antitumor effects of BA are related to the downregulation of cycli D and Bcl-xL expressions [13]. Studies have demonstrated that BA shows antimetastatic effects by inhibiting epithelial mesenchymal transition (EMT) [14].…”

Section: Introductionmentioning

confidence: 99%

Approaches to Improve the Oral Bioavailability and Effects of Novel Anticancer Drugs Berberine and Betulinic Acid

et al. 2014

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BackgroundThe poor bioavailability of Berberine (BBR) and Betulinic acid (BA) limits the development of these promising anticancer agents for clinical use. In the current study, BBR and BA in spray dried (SD) mucoadhesive microparticle formulations were prepared.MethodsA patented dual channel spray gun technology established in our laboratory was used for both formulations. Gastrointestinal (GI) permeability studies were carried out using Caco-2 cell monolayer grown in in-vitro system. The oral bioavailability and pharmacokinetic profile of SD formulations were studied in Sprague Dawley rats. A549 orthotopic and H1650 metastatic NSCLC models were utilized for the anticancer evaluations.ResultsPharmacokinetic studies demonstrated that BBR and BA SD formulations resulted in 3.46 and 3.90 fold respectively, significant increase in plasma Cmax concentrations. AUC levels were increased by 6.98 and 7.41 fold in BBR and BA SD formulations, respectively. Compared to untreated controls groups, 49.8 & 53.4% decrease in the tumor volumes was observed in SD formulation groups of BBR and BA, respectively. Molecular studies done on excised tumor (A549) tissue suggested that BBR in SD form resulted in a significant decrease in the survivin, Bcl-2, cyclin D1, MMP-9, HIF-1α, VEGF and CD31 expressions. Cleaved caspase 3, p53 and TUNEL expressions were increased in SD formulations. The RT-PCR analysis on H1650 tumor tissue suggested that p38, Phospho-JNK, Bax, BAD, cleaved caspase 3&8 mRNA expressions were significantly increased in BA SD formulations. Chronic administration of BBR and BA SD formulations did not show any toxicity.ConclusionsDue to significant increase in oral bioavailability and superior anticancer effects, our results suggest that spray drying is a superior alternative formulation approach for oral delivery of BBR and BA.

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“…In addition, we showed that these properties are enhanced in BA5 derivative. In fact, the antiproliferative effect of BA and other terpenoids is well recognized in different tumor cell lines, especially in leukemia lineages, such as Jurkat cells, in which BA treatment induced cell cycle arrest in pre-G1 phase followed by cell death by apoptosis (Chen et al, 2008). Interestingly, a similar pathway of cell death was observed in lymphocytes treated with BA5.…”

Section: Discussionmentioning

confidence: 89%