Sensitive method for determination of piplartine, an alkaloid amide from Piper species, in rat plasma samples by liquid chromatography-tandem mass spectrometry

Bezerra, Daniel P.; Pessoa, Cláudia; Moraes, M. O.; Costa-Lotufo, Letı́cia V.; Gouvea, Dayana Rubio; Jabor, Valquíria Aparecida Polisel; Lopes, Norberto Peporine; Borges, Keyller Bastos; Lima, Mary Anne Sousa; Silveira, Edilberto R.

doi:10.1590/s0100-40422012000300004

Cited by 14 publications

(7 citation statements)

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“…Piplartine (piperlongumine) is a plant-derived compound found in some Piper species that became a novel potential antineoplastic agent. Potent cytotoxicity, genotoxicity, antitumor, antiangiogenic and antimetastatic properties, in addition to presenting adequate bioavailability and safety profile have been attributed for this molecule and its derivatives [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] . Although its cytotoxic properties have been known for over three decades, the great interest in this molecule has arisen after its cytotoxicity and ability to induce the production of reactive oxygen species (ROS) selectively in cancer cells were described [11] , [12] .…”

Section: Introductionmentioning

confidence: 99%

A novel platinum complex containing a piplartine derivative exhibits enhanced cytotoxicity, causes oxidative stress and triggers apoptotic cell death by ERK/p38 pathway in human acute promyelocytic leukemia HL-60 cells

et al. 2019

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Piplartine (piperlongumine) is a plant-derived compound found in some Piper species that became a novel potential antineoplastic agent. In the present study, we synthesized a novel platinum complex containing a piplartine derivative cis-[PtCl(PIP-OH)(PPh3)2]PF6 (where, PIP-OH = piplartine demethylated derivative; and PPh3 = triphenylphosphine) with enhanced cytotoxicity in different cancer cells, and investigated its apoptotic action in human promyelocytic leukemia HL-60 cells. The structure of PIP-OH ligand was characterized by X-ray crystallographic analysis and the resulting platinum complex was characterized by infrared, molar conductance measurements, elemental analysis and NMR experiments. We found that the complex is more potent than piplartine in a panel of cancer cell lines. Apoptotic cell morphology, increased internucleosomal DNA fragmentation, without cell membrane permeability, loss of the mitochondrial transmembrane potential, increased phosphatidylserine externalization and caspase-3 activation were observed in complex-treated HL-60 cells. Treatment with the complex also caused a marked increase in the production of reactive oxygen species (ROS), and the pretreatment with N-acetyl-L-cysteine, an antioxidant, reduced the complex-induced apoptosis, indicating activation of ROS-mediated apoptosis pathway. Important, pretreatment with a p38 MAPK inhibitor (PD 169316) and MEK inhibitor (U-0126), known to inhibit ERK1/2 activation, also prevented the complex-induced apoptosis. The complex did not induce DNA intercalation in cell-free DNA assays. In conclusion, the complex exhibits more potent cytotoxicity than piplartine in a panel of different cancer cells and triggers ROS/ERK/p38-mediated apoptosis in HL-60 cells.

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Section: Introductionmentioning

confidence: 99%

A novel platinum complex containing a piplartine derivative exhibits enhanced cytotoxicity, causes oxidative stress and triggers apoptotic cell death by ERK/p38 pathway in human acute promyelocytic leukemia HL-60 cells

et al. 2019

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“…Some pharmacological studies have reported larvicidal [3], molluscicidal [4], and gastroprotective [5] activities of extracts and fractions of P. tuberculatum. Phytochemical analyses of P. tuberculatum extracts have identified the presence of a variety of amides with different biological activities [1,2,[5][6][7]. Among these compounds, piplartine, also known as piperlongumine, is the most commonly studied.…”

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confidence: 99%

Antitumour Efficacy of Piper tuberculatum and Piplartine Based on the Hollow Fiber Assay

et al. 2014

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Piper tuberculatum, popularly known in Brazil as "jaborandi falso" and "pimenta darta", is widely used in folk medicine for the treatment of several diseases. In this study, the in vivo hollow fiber assay was used to investigate the antitumour efficacy of the crude extract and piplartine obtained from P. tuberculatum roots. Human glioblastoma (SF-295) and colon carcinoma (HCT-8) cell lines were used. In vitro cytotoxicity was assayed by the MTT assay. In the hollow fiber assay, nude mice implanted with tumour cells in hollow fibers were treated for four consecutive days via the intraperitoneal route, and tumour cell populations were assessed by the MTT assay. Both the crude extract and piplartine displayed cytotoxicity. In the hollow fiber assay, tumour growth inhibition rates were 24.6-54.8 % for the crude extract and 33.7-62.2 % for piplartine. No signal of toxicity was noticed. In conclusion, the crude extract and piplartine obtained from P. tuberculatum roots displayed in vitro and in vivo anticancer efficacy.

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“…First, we have determined whether PL is toxic to human T cells. To this end, we prepared freshly isolated human PBTs and assessed T cell viability after treatment with 10 µM PL up to 24 h. Since, it was reported that 1511.9 ng/ml (4.8 µM) of PL could be found in rat plasma after 1 dose of 50 mg/kg PL intraperitoneal injection (36), in our study we considered concentrations of PL up to 10 µM as physiologically relevant. Even the highest PL concentration used in our experiments (10 µM) showed no significant cytotoxicity on primary human T cells ( Supplementary Figure 2a).…”

Section: Pl Induces a Prooxidative Milieu In Primary Human T Cellsmentioning

confidence: 99%

Piperlongumine Acts as an Immunosuppressant by Exerting Prooxidative Effects in Human T Cells Resulting in Diminished TH17 but Enhanced Treg Differentiation

et al. 2020

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Piperlongumine (PL), a natural small molecule derived from the Piper longum Linn plant, has received growing interest as a prooxidative drug with promising anticancer properties. Yet, the influence of PL on primary human T cells remained elusive. Knowledge of this is of crucial importance, however, since T cells in particular play a critical role in tumor control. Therefore, we investigated the effects of PL on the survival and function of primary human peripheral blood T cells (PBTs). While PL was not cytotoxic to PBTs, it interfered with several stages of T cell activation as it inhibited T cell/APC immune synapse formation, co-stimulation-induced upregulation of CD69 and CD25, T cell proliferation and the secretion of proinflammatory cytokines. PL-induced immune suppression was prevented in the presence of thiol-containing antioxidants. In line with this finding, PL increased the levels of intracellular reactive oxygen species and decreased glutathione in PBTs. Diminished intracellular glutathione was accompanied by a decrease in S-glutathionylation on actin suggesting a global alteration of the antioxidant response. Gene expression analysis demonstrated that T H 17-related genes were predominantly inhibited by PL. Consistently, the polarization of primary human naïve CD4 + T cells into T H 17 subsets was significantly diminished while differentiation into T reg cells was substantially increased upon PL treatment. This opposed consequence for T H 17 and T reg cells was again abolished by thiol-containing antioxidants. Taken together, PL may act as a promising agent for therapeutic immunosuppression by exerting prooxidative effects in human T cells resulting in a diminished T H 17 but enhanced T reg cell differentiation.

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Sensitive method for determination of piplartine, an alkaloid amide from Piper species, in rat plasma samples by liquid chromatography-tandem mass spectrometry

Cited by 14 publications

References 4 publications

A novel platinum complex containing a piplartine derivative exhibits enhanced cytotoxicity, causes oxidative stress and triggers apoptotic cell death by ERK/p38 pathway in human acute promyelocytic leukemia HL-60 cells

A novel platinum complex containing a piplartine derivative exhibits enhanced cytotoxicity, causes oxidative stress and triggers apoptotic cell death by ERK/p38 pathway in human acute promyelocytic leukemia HL-60 cells

Antitumour Efficacy of Piper tuberculatum and Piplartine Based on the Hollow Fiber Assay

Piperlongumine Acts as an Immunosuppressant by Exerting Prooxidative Effects in Human T Cells Resulting in Diminished TH17 but Enhanced Treg Differentiation

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