3β-acetyl tormentic acid induces apoptosis of resistant leukemia cells independently of P-gp/ABCB1 activity or expression

Rocha, Gleice da Graça; Simões, Marisol; Oliveira, Rodrigo Rodrigues de; Kaplan, Maria Auxiliadora Coelho; Gattass, Cerli Rocha

doi:10.1007/s10637-010-9524-1

Cited by 16 publications

(10 citation statements)

References 36 publications

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“…Therefore, new therapies, able to overcome mechanisms of drug resistance, should be of interest for GBM treatment. In recent years, several substances isolated from plants were shown to modulate drug resistance in cancer cells (12)(13)(14). We have previously shown that the M. officinalis EO was active against several cancer cell lines (1), including a drug-resistant lung cancer cell line.…”

Section: Officinalis Eo Induces Apoptosis In Glioblastoma mentioning

confidence: 99%

Apoptosis-Inducing Effects ofMelissa officinalisL. Essential Oil in Glioblastoma Multiforme Cells

Queiroz

Takiya

Guimarães

et al. 2014

Cancer Investigation

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Current therapies for glioblastoma multiforme (GBM) are not effective. This study investigated the activity of the M. officinalis essential oil (EO) and its major component (citral) in GBM cell lines. Both EO and citral decreased the viability and induced apoptosis of GBM cells as demonstrated by DNA fragmentation and caspase-3 activation. Antioxidant prevented citral-induced death, indicating its dependence on the production of reactive oxygen species. Citral downmodulated the activity and inhibited the expression of multidrug resistance associated protein 1 (MRP1). These results show that EO, through its major component, citral, may be of potential interest for the treatment of GBM.

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Section: Officinalis Eo Induces Apoptosis In Glioblastoma mentioning

confidence: 99%

Apoptosis-Inducing Effects ofMelissa officinalisL. Essential Oil in Glioblastoma Multiforme Cells

Queiroz

Takiya

Guimarães

et al. 2014

Cancer Investigation

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“…In a previous study, we showed that 3ATA induced apoptosis in P-gp/ABCB1-expressing cell lines without interfering with pump activity [27]. Herein, we used the MTT assay to evaluate the cytotoxicity of this triterpene against MRP1/ABCC1-expressing cell lines.…”

Section: Resultsmentioning

confidence: 99%

“…We investigated the effect of triterpenes isolated from Cecropia lyratiloba on cells expressing MDR proteins and demonstrated that these triterpenes are not substrates for the P-gp/ABCB1 protein [27]. This study shows that 3ATA (3β-acetyl tormentic acid), one of the triterpenes isolated from this plant, is able to kill MRP1/ABCC1-expressing cells (Figures 2A and 3).…”

Section: Resultsmentioning

confidence: 99%

“…Pentacyclic triterpenes have recently been emerging as a class of antitumoral substances with anti-MDR properties [23–26]. In a previous study [27], we showed that 3β-acetyl tormentic acid (3ATA, Figure 1), a triterpene isolated from Cecropia lyratiloba , is able to induce apoptosis in an MDR leukemia cell line overexpressing P-gp/ABCB1 without interfering with P-gp/ABCB1 expression or activity. The aim of the present work was to study the interactions of 3ATA with members of the MRP/ABCC family and, thus, to build a profile of the activity of this compound with respect to this transporter family.…”

Section: Introductionmentioning

confidence: 97%

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Effects of 3β-Acethyl Tormentic Acid (3ATA) on ABCC Proteins Activity

Rocha

Simões

Oliveira

et al. 2012

IJMS

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Multidrug resistance (MDR) is considered the main cause of cancer chemotherapy failure and patient relapse. The active drug efflux mediated by transporter proteins of the ABC (ATP-binding cassette) family is the most investigated mechanism leading to MDR. With the aim of inhibiting this transport and circumventing MDR, a great amount of work has been dedicated to identifying pharmacological inhibitors of specific ABC transporters. We recently showed that 3β-acetyl tormentic acid (3ATA) had no effect on P-gp/ABCB1 activity. Herein, we show that 3ATA strongly inhibited the activity of MRP1/ABCC1. In the B16/F10 and Ma104 cell lines, this effect was either 20X higher or similar to that observed with MK571, respectively. Nevertheless, the low inhibitory effect of 3ATA on A549, a cell line that expresses MRP1-5, suggests that it may not inhibit other MRPs. The use of cells transfected with ABCC2, ABCC3 or ABCC4 showed that 3ATA was also able to modulate these transporters, though with an inhibition ratio lower than that observed for MRP1/ABCC1. These data point to 3ATA as a new ABCC inhibitor and call attention to its potential use as a tool to investigate the function of MRP/ABCC proteins or as a co-adjuvant in the treatment of MDR tumors.

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“…For apoptosis and cell cycle assays, a 1 μM IM dose was used. Cells were treated with 1 μM IM, 50 μM VP [79] and co-treated with 1 μM IM and 50 μM VP for apoptosis, cell cycle and Pgp activity assays. K562 cells were used as positive control for Rho 123 retention and K562 cells treated with 1 μM IM were used as positive control for apoptosis induction and cell cycle arrest.…”

Section: Methodsmentioning

confidence: 99%

A comparative proteomic study identified LRPPRC and MCM7 as putative actors in imatinib mesylate cross-resistance in Lucena cell line

et al. 2012

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BackgroundAlthough chronic myeloid leukemia (CML) treatment has improved since the introduction of imatinib mesylate (IM), cases of resistance have been reported. This resistance has been associated with the emergence of multidrug resistance (MDR) phenotype, as a BCR-ABL independent mechanism. The classic pathway studied in MDR promotion is ATP-binding cassette (ABC) family transporters expression, but other mechanisms that drive drug resistance are largely unknown. To better understand IM therapy relapse due to the rise of MDR, we compared the proteomic profiles of K562 and Lucena (K562/VCR) cells.ResultsThe use of 2-DE coupled with a MS approach resulted in the identification of 36 differentially expressed proteins. Differential mRNA levels of leucine-rich PPR motif-containing (LRPPRC) protein, minichromosome maintenance complex component 7 (MCM7) and ATP-binding cassette sub-family B (MDR/TAP) member 1 (ABCB1) were capable of defining samples from CML patients as responsive or resistant to therapy.ConclusionsThrough the data presented in this work, we show the relevance of MDR to IM therapy. In addition, our proteomic approach identified candidate actors involved in resistance, which could lead to additional information on BCR-ABL-independent molecular mechanisms.

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3β-acetyl tormentic acid induces apoptosis of resistant leukemia cells independently of P-gp/ABCB1 activity or expression

Cited by 16 publications

References 36 publications

Apoptosis-Inducing Effects ofMelissa officinalisL. Essential Oil in Glioblastoma Multiforme Cells

Apoptosis-Inducing Effects ofMelissa officinalisL. Essential Oil in Glioblastoma Multiforme Cells

Effects of 3β-Acethyl Tormentic Acid (3ATA) on ABCC Proteins Activity

A comparative proteomic study identified LRPPRC and MCM7 as putative actors in imatinib mesylate cross-resistance in Lucena cell line

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