Monica Pereira - Academia.edu (original) (raw)

Papers by Monica Pereira

Natural Product Communications, 2014

Current Traditional Medicine, 2015

Oncology Letters, 2010

Plant-derived compounds are important sources of effective anti-cancer agents. Pterodon pubescens... more Plant-derived compounds are important sources of effective anti-cancer agents. Pterodon pubescens is a native Brazilian plant popularly known for its anti-inflammatory and anti-arthritic effects. The ethanolic extract of its seeds (EEPp) is a viscous, brown and fragrant oil containing geranylgeraniol, farnesol, naphthalene, dimethyldodecatrienol and vouacapan diterpene derivatives, in addition to other compounds. This study investigated the in vitro anti-leukemic properties of EEPp using the resistant human leukemia cell line K562. The EEPp anti-proliferative effect was demonstrated by the inhibition of DNA synthesis and cell growth, and the induction of cell cycle arrest in the G 1 phase. Furthermore, cyclin E2 mRNA levels were down-regulated, while those of cyclin D1 were up-regulated. An EEPp anti-leukemic effect may have also triggered apoptosis, as it increased the number of shrunken cells and phosphatidylserine cell membrane exposure. These observations suggest that EEPp deregulates cyclin D1 and E2 expression, inducing cell cycle arrest and apoptosis of leukemic cells.

$Research paper thumbnail of Terpenic subfraction of Pterodon pubescens induces apoptosis of K562 leukemic cells by modulating gene expression$

Oncology Reports, 2010

Deregulation of cell proliferation and apoptosis is linked to malignant cell development. Leukemi... more Deregulation of cell proliferation and apoptosis is linked to malignant cell development. Leukemia is the most frequent cancer in children, and plants are important sources for new potential anti-cancer agents. Although anti-tumoral effects have been shown for Pterodon pubescens extracts, the mechanisms are still obscure. This study describes in Pterodon pubescens a furane diterpene only reported in Pterodon polygalaeflorus, the methyl-6α-acetoxy-7β-hydroxyvouacapan-17β-oate, indicated by HRMS and 13C-NMR analysis, and demonstrates some mechanisms of the anti-leukemia action of its terpene subfraction SF5. SF5 induced cytotoxic and anti-proliferative effects on K562 cells. Increased sub-G1 nuclei and Annexin V+-FITC cells confirmed apoptosis of leukemic cells by treatment of these cells with SF5. Down-regulation of DNMT1 gene transcription and over-expression of Apaf-1 mRNA suggested that SF5 may be inducing apoptosis of K562 cells by epigenetic up-regulation of pro-apoptotic proteins involved in the mitochondrial intrinsic pathway.

Journal of Biochemical and Biophysical Methods, 2002

Phosphofructokinase-1 plays a key role in the regulation of carbohydrate metabolism. Its activity... more Phosphofructokinase-1 plays a key role in the regulation of carbohydrate metabolism. Its activity can be used as an indicator of the glycolytic flux in a tissue sample. The method most commonly employed to determine phosphofructokinase-1 activity is based on oxidation of NADH by the use of aldolase, triosephosphate isomerase, and a-glycerophosphate dehydrogenase. This method suffers from several disadvantages, including interactions of the auxiliary enzymes with phosphofructokinase-1. Other methods that have been used also require auxiliary enzymes or are less sensitive than a coupled assay. Here, we propose a direct method to determine phosphofructokinase-1 activity, without the use of auxiliary enzymes. This method employs fructose-6-phos-32 Žw 32 x . phate and ATP labeled with P in the gamma position g-P ATP , and leads to the formation 32 Žw 32 x . of ADP and fructose-1,6-bisphosphate labeled with P 1-P fructose-1,6-bisphosphate . Actiw 32 x vated charcoal is used to adsorb unreacted g-P ATP, and the radioactive product in the w 32 x supernatant, 1-P fructose-1,6-bisphosphate, is analyzed on a liquid scintillation counter. The proposed method is precise and relatively inexpensive, and can be applied to determine phosphofructokinase-1 activity in cellular extracts as well as in the purified enzyme. q M. Sola-Penna . 0165-022Xr02r$ -see front matter q 2002 Elsevier Science B.V. All rights reserved.

$Research paper thumbnail of Terpenic fraction of Pterodon pubescens inhibits nuclear factor kappa B and extracellular signal-regulated protein Kinase 1/2 activation and deregulates gene expression in leukemia cells$

BMC Complementary and Alternative Medicine, 2012

Background: Plant derived compounds have been shown to be important sources of several anti-cance... more Background: Plant derived compounds have been shown to be important sources of several anti-cancer agents. As cell cycle deregulation and tumor growth are intimately linked, the discovery of new substances targeting events in this biochemical pathway would be of great value. The anti-leukemic effect of an ethanolic extract of Pterodon pubescens seeds (EEPp) has been previously demonstrated and now we show that a terpenic subfraction (SF5) of EEPp containing farnesol, geranylgeraniol and vouacapan derivatives induces apoptosis in the human chronic myelogenous leukemia cell line K562. This work addresses SF5's antiproliferative mechanisms in these cells since they are still unclear. Methods: DNA synthesis in K562 cells was assessed by [ 3 H]-methyl-thymidine incorporation and cell cycle status by flow cytometry. The expression of cyclins D1 and E2, of the cell cycle inhibitor p21 and of the proto-oncogene c-myc was evaluated by semi-quantitative RT-PCR. Extracellular-signal-regulated kinases (ERK) 1/2 and nuclear factor kappa B (NF-κB) activation was evaluated by western blotting.

$Research paper thumbnail of Antitumor screening of Pterodon pubescens terpenic fraction indicates high sensitivity for lymphocytic leukemia cells$

Natural Product Communications, Nov 1, 2014

Cancer is the second leading cause of human mortality worldwide. Therefore, the search for new dr... more Cancer is the second leading cause of human mortality worldwide. Therefore, the search for new drugs or alternative therapy strategies has been required. Anticancer agents have been developed from plants since the 1950s and natural products still represent an important source of new and promising bioactive molecules. This work describes the cytotoxic effects of SF5 on tumor cells of high prevalence in the world and investigated some mechanisms of its antitumor action. The antitumor screening was performed with human lung carcinoma (A549), human breast (MCF-7) and prostate (PC-3) adenocarcinoma and chronic myeloid and acute lymphocytic leukemia cell lines. The acute lymphocytic leukemia Jurkat cells presented high sensitivity to the cytotoxic effects of SF5 (inhibition of 85-90%), compared with either the chronic myeloid leukemia K562 or solid tumor cell lines (lung, breast and prostate). SF5 arrested the cell cycle in G1 phase, which may be related with the observed downregulation of mRNA expression of c-Myc transcription factor at 24 h and 36 h. SF5 treatment induced cytochrome c release from mitochondria to cytosol, leading the Jurkat cells into apoptosis, which was evidenced by the internucleosomal fragmented DNA and increased number of annexin V-FITC positive cells. The SF5 showed high cytotoxicity for lymphocytic leukemia cells and low or none for solid tumor cells, without toxicity for peripheral mononuclear cells of healthy humans. SF5 altered gene expression, arrested the cell cycle and induced apoptosis via the mitochondrial pathway, similar to traditional antineoplastic chemotherapeutic drugs.