The contralateral kidney presents with impaired mitochondrial functions and disrupted redox homeostasis after 14 days of unilateral ureteral obstruction in mice.

In unilateral ureteral obstruction (UUO), both oxidative stress and mitochondrial dysfunction are related to cell death. The aim of this study has been to characterize profiles of enzyme antioxidant activities and mitochondrial functioning of the contralateral (CL) compared to UUO and Sham (false-operated) kidneys of Balb/c mice. Kidneys were resected 14 days after obstruction for immunohistochemical and cortical mitochondrial functioning assays.

Pomolic acid exhibits anticancer potential against a docetaxel‑resistant PC3 prostate cell line.

Prostate cancer (PC) is one of the leading causes of cancer‑related death in the male population worldwide. Mortality of PC is dependent on tumor recurrence and its progression to metastatic disease. We examined the effects of pentacyclic triterpene pomolic acid (PA) on docetaxel‑resistant PC3 cells.

Antitumor Effect of Pomolic Acid in Acute Myeloid Leukemia Cells Involves Cell Death, Decreased Cell Growth and Topoisomerases Inhibition.

Background: Acute myeloid leukemia (AML) represents the largest number of annual deaths from hematologic malignancy. In the United States, it was estimated that 21.380 individuals would be diagnosed with AML and 49.

Pomolic acid induces apoptosis and inhibits multidrug resistance protein MRP1 and migration in glioblastoma cells.

Glioblastoma (GBM), the most aggressive of primary brain tumors, determine short survival and poor quality of life. Therapies used for its treatment are not effective and chemotherapy failure is partially due to multidrug resistance (MDR) mechanisms present in the tumor cells. New therapeutic strategies are needed in order to improve survival in GBM.

Ultrasound-assisted Extraction of Ursolic Acid from the Flowers of Linn (Rubiaceae) and Antiproliferative Activity of Ursolic Acid and Synthesized Derivatives.

Background: Linn (Rubiaceae) is an evergreen shrub with bright scarlet colored flowers found in several tropical and subtropical countries. It is used as an ornamental and medicinal plant. Phytochemical studies revealed that its major special metabolites are triterpene acids, such as ursolic and oleanolic acid.

Oleanolic acid (OA) as an antileishmanial agent: Biological evaluation and in silico mechanistic insights.

Although a worldwide health problem, leishmaniasis is considered a highly neglected disease, lacking efficient and low toxic treatment. The efforts for new drug development are based on alternatives such as new uses for well-known drugs, in silico and synthetic studies and naturally derived compounds. Oleanolic acid (OA) is a pentacyclic triterpenoid widely distributed throughout the Plantae kingdom that displays several pharmacological activities.

3β-Acetyl tormentic acid reverts MRP1/ABCC1 mediated cancer resistance through modulation of intracellular levels of GSH and inhibition of GST activity.

ABC transporter overexpression is an important mechanism of multidrug resistance (MDR) and one of the main obstacles to successful cancer treatment. As these proteins actively remove chemotherapeutics from the tumor cells, the pharmacological inhibition of their activity is a possible strategy to revert drug resistance. Moreover, the ability of MDR inhibitors to sensitize resistant cells to conventional drugs is important for their clinical use.

Apoptosis-inducing effects of Melissa officinalis L. essential oil in glioblastoma multiforme cells.

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.

Oleanolic acid improves pulmonary morphofunctional parameters in experimental sepsis by modulating oxidative and apoptotic processes.

We compared the effects of oleanolic acid (OA) vs. dexamethasone on lung mechanics and histology, inflammation, and apoptosis in lung and distal organs in experimental sepsis. Seventy-eight BALB/c mice were randomly divided into two groups.

Effects of 3β-acethyl tormentic acid (3ATA) on ABCC proteins activity.

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.

Oleanolic acid initiates apoptosis in non-small cell lung cancer cell lines and reduces metastasis of a B16F10 melanoma model in vivo.

Background: Drug resistance, a process mediated by multiple mechanisms, is a critical determinant for treating lung cancer. The aim of this study is to determine if oleanolic acid (OA), a pentacyclic triterpene present in several plants, is able to circumvent the mechanisms of drug resistance present in non-small cell lung cancer (NSCLC) cell lines and to induce their death.

Principal Findings: OA decreased the cell viability of the NSCLC cell lines A459 and H460 despite the presence of active, multidrug-resistant (MDR) MRP1/ABCC1 proteins and the anti-apoptotic proteins Bcl-2 and survivin.

Effects of oleanolic acid on pulmonary morphofunctional and biochemical variables in experimental acute lung injury.

We analysed the effects of oleanolic acid (OA) on lung mechanics and histology and its possible mechanisms of action in experimental acute lung injury (ALI). BALB/c mice were randomly divided into Control (saline, ip) and ALI (paraquat, 25 mg/kg, ip) groups. At 1 h, both groups were treated with saline (SAL, 50 μl ip), OA (10 mg/kg ip), or dexamethasone (DEXA, 1 mg/kg ip).

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

Chronic myeloid leukemia (CML) is a potentially fatal stem-cell cancer. P-glycoprotein (P-gp/ABCB1) activity has been described as a relevant factor in the chemotherapeutic failure and correlated to a poor prognosis in these malignancies. In the present study, we investigated the mechanism of the antineoplastic activity of 3β-acetyl tormentic acid (3ATA), a triterpene isolated from C.

Individual prognostic assessment in the intensive care unit: can therapeutic persistence be distinguished from therapeutic obstinacy?

Objectives: Availability of state-of-the-art technology at intensive care units has often turned into a tool aggravating suffering by prolonging the end-of-life process. Distinguishing therapeutic persistence from therapeutic obstinacy has become a great challenge for present-day medicine. The aim of this study was to assess the benefit-harm relation in the use of life-sustaining therapies by means of an evolutionary system of individual prognostic assessment.

Betulinic acid does not modulate the activity of P-gp/ABCB1 or MRP1/ABCC1 in a non-tumoral renal cell line: Possible utility in multidrug resistance cancer chemotherapy.

Multidrug resistance (MDR) is a multifactorial phenomenon considered to be the main cause of failure in cancer chemotherapy. One of the underlying mechanisms of MDR is the overexpression of membrane transporter proteins, such as P-glycoprotein (P-gp/ABCB1) and multidrug resistance-associated protein 1 (MRP1/ABCC1). As these proteins are also expressed in normal tissues, considerable attention has been dedicated to the search for cytotoxic drugs that are not substrates for these proteins.

Topological polar surface area defines substrate transport by multidrug resistance associated protein 1 (MRP1/ABCC1).

Multidrug resistance-associated protein 1 (MRP1/ABCC1) is a very promiscuous transporter. Herein we used topological polar surface area (TPSA), a descriptor defined as the sum of surfaces of polar atoms in a molecule, to analyze drug transport by MRP1. We suggested that compounds with high TPSA are transported while those with low TPSA are not.

Ras pathway activation in gliomas: a strategic target for intranasal administration of perillyl alcohol.

Introduction: Targeted therapy directed at specific molecular alterations is already creating a shift in the treatment of cancer patients. Malignant gliomas commonly overexpress the oncogenes EGFR and PDGFR and contain mutations and deletions of the tumor suppressor genes PTEN and TP53. Some of these alterations lead to activation of the P13K/Akt and Ras/MAPK pathways, which provide targets for therapy.

Antitumoral activity of new polyamine-naphthoquinone conjugates.

Polyamine-naphthoquinone conjugates 5a-c were synthesized by nucleophilic displacement of 2-methoxy-lawsone 3a, 2-methoxylapachol 3b and 2-methoxy-nor-lapachol 3c with the polyamine N1-Boc-N5-Bn-spermidine 4. Unprotected derivatives 6a-c were synthesized to evaluate the effect of the protective Boc group on the activity of compounds 5a-c. The colorimetric MTT assay was used to evaluate their cytotoxic activity.

Natural triterpenoids from Cecropia lyratiloba are cytotoxic to both sensitive and multidrug resistant leukemia cell lines.

The cytotoxicity of four triterpenoids, euscaphic acid (1), tormentic acid (2), 2alpha-acetyl tormentic acid (3), and 3beta-acetyl tormentic acid (4), isolated from the roots of Cecropia lyratiloba (Moraceae) by countercurrent chromatography, was evaluated in vitro in sensitive and multidrug resistant leukemia cell lines. A structure/activity relationship analysis of the compounds was performed. Acetylation of compound 2 at C2 increased its activity by a factor of 2 while acetylation at C3 had a smaller effect.

The husk fiber of Cocos nucifera L. (Palmae) is a source of anti-neoplastic activity.

In the present study, we investigated the in vitro anti-tumoral activities of fractions from aqueous extracts of the husk fiber of the typical A and common varieties of Cocos nucifera (Palmae). Cytotoxicity against leukemia cells was determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Cells (2 x 10(4)/well) were incubated with 0, 5, 50 or 500 microg/mL high- or low-molecular weight fractions for 48 h, treated with MTT and absorbance was measured with an ELISA reader.

Pomolic acid-induced apoptosis in cells from patients with chronic myeloid leukemia exhibiting different drug resistance profile.

Pomolic acid (PA) is a pentacyclic triterpene which has been previously described as active in inhibiting the growth of K562 cell line-originated from chronic myeloid leukemia (CML) in blast crisis-and its vincristine-resistant derivative K562-Lucena1. In this work, cells from CML patients were treated with PA and the apoptotic index was compared with the multidrug resistance (MDR) profile and clinical status of the patients. Our findings show that PA 12.

Anaplastic oligodendroglioma responding favorably to intranasal delivery of perillyl alcohol: a case report and literature review.

Background: In recent years, molecular genetics and biology are exerting significant influence on the practice of neuro-oncology, with oligodendrogliomas being the most prominent example. To explore therapeutic strategies and evaluate the clinical results, we report a case of a patient with anaplastic oligodendroglioma managed with intranasal delivery of POH.

Case Description: A 62 year-old white woman presented with complaints of seizures and frontal headache in June 1999.

Effects of perillyl alcohol and heat shock treatment in gene expression of human lung adenocarcinoma cell line A549.

The K-Ras protein is found mutated in 42.4% of lung adenocarcinoma cases, evidencing its importance as a chemotherapeutic target. The Ras protein becomes functional after farnesylation, a post-transduction modification, allowing its attachment to the cellular membrane permitting signal transduction.

Oleanolic acid inhibits the activity of the multidrug resistance protein ABCC1 (MRP1) but not of the ABCB1 (P-glycoprotein): possible use in cancer chemotherapy.

The effects of oleanolic acid (OA) on ABCB1 and ABCC1 activities were studied in a cell line constitutively expressing both proteins. It was observed that OA did not alter ABCB1 activity, but inhibited the activity of ABCC1 protein. This inhibition was reversible and only occurred in the presence of OA.