scholarly journals Effects of the Latex of Synadenium grantii Hook F. (Euphorbiaceae) on a Preclinical Model of Canine Prostate Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Eric Saymom Andrade Brito ◽  
Laís Di Paulie Taborda Prado ◽  
Liana Késia Costa Araújo ◽  
Emmanuel Arnhold ◽  
Moema Pacheco Chediak Matos ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bioactive Compounds ◽  
Phorbol Esters ◽  
Scientific Evidence ◽  
Preclinical Model ◽  
Antitumor Effects ◽  
Carcinoma Cell Lines ◽  
Diphenyltetrazolium Bromide ◽  
Natural Drugs

Prostatic cancer (PC) stands out in terms of its occurrence, pathophysiology, and unfavorable prognostics in humans and dogs. Natural drugs bear an integrative potential for conventional antineoplastic treatments. In this context, the bioproducts of Synadenium grantii have been empirically used in different parts of Brazil for the integrative treatment of prostate cancer in humans. However, there is no availability of scientific evidence of the antitumor effects of S. grantii. Therefore, this study aimed to investigate the bioactive compounds in the latex of S. grantii using the high-resolution mass spectrophotometry (HRMS) and to evaluate its cytotoxic effects on primary canine PC cell cultures. Four fragments of phorbol ester were identified as potential bioactive compounds using the HRMS. With the help of an MTT ([3-(4,5-dimethyldiazol-2-yl)-2,5 diphenyltetrazolium bromide]) assay, two canine prostatic carcinoma cell lines (PC 1 and PC2) showed a decrease in the tumor cell count, with an Inhibitory concentration 50 (IC50)of 0.8469 and 0.6068 mg/ml, respectively, for PC1 and PC2. In conclusion, the latex of S. grantii contains phorbol esters in its composition, and its aqueous solution has a cytotoxic effect on canine metastatic PC cells in vitro.

scholarly journals Leaves and decoction of Juglans regia L.: Different performances regarding bioactive compounds and in vitro antioxidant and antitumor effects

2013 ◽  
Vol 51 ◽  
pp. 430-436 ◽  
Author(s):  
André Santos ◽  
Lillian Barros ◽  
Ricardo C. Calhelha ◽  
Montserrat Dueñas ◽  
Ana Maria Carvalho ◽  
...  
Keyword(s):  
Bioactive Compounds ◽  
Juglans Regia ◽  
Antitumor Effects

Effect of a therapeutic sphingosine 1-phosphate antibody on intratumoral hypoxia and standard chemotherapy in a preclinical model of prostate cancer.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 223-223 ◽  
Author(s):  
Olivier Cuvillier ◽  
Isabelle Ader ◽  
Pierre Bouquerel ◽  
Roger Allen Sabbadini ◽  
Bernard Malavaud
Keyword(s):  
Prostate Cancer ◽  
Xenograft Model ◽  
Tumor Oxygenation ◽  
Adaptation To Hypoxia ◽  
Preclinical Model ◽  
Autocrine Signaling ◽  
Multiple Cancer ◽  
Response To Chemotherapy ◽  
Sphingosine 1 Phosphate

223 Background: Hypoxia promotes vascularization, metastasis and resistance to treatments. The activation of HIF-1α is identified as the master mechanism of adaptation to hypoxia. We recently identified the sphingosine kinase 1/sphingosine 1- phosphate (SphK1/S1P) pathway as a new modulator of HIF-1α activity under hypoxia in multiple cancer cell models (Ader et al, Cancer Res, 2008). S1P elicits proliferation, survival, or angiogenesis, and is believed to exert most of its actions as a ligand for a family of specific GPCRs to elicit paracrine or autocrine signaling. We have suggested that inhibiting SphK1/S1P signaling, which is upregulated under hypoxia, may normalize the microenvironment and increase sensitivity to chemotherapy, in the broader concept of «normalization of tumor vessels» as tumor oxygenation is known to enhance response to chemotherapy (Ader et al., Cancer Res, 2009). Methods: Quantitation of hypoxia and angiogenesis, and treatment efficacy using an orthotopic (o.t) xenograft model of fluorescent HRPC cells. Results: We provide in vitro evidence that inhibiting the S1P exogenous signaling, through pharmacological inhibition of its receptors or by taking advantage of a monoclonal antibody neutralizing S1P, blocks HIF-1α accumulation and its activity in prostate cancer cells under hypoxia. Second, using an o.t model of prostate cancer, we show that an anti-S1P antibody inhibits intratumoral hypoxia, modifies vessel architecture and improves tumor perfusion within 5 days of treatment. Third, we demonstrate that an anti-S1P strategy sensitizes to docetaxel, the ’gold standard’ treatment for HRPC. A 5-day anti-S1P antibody pretreatment markedly sensitizes to docetaxel in an o.t. PC-3/GFP model established in nude mice. The combination anti-S1P antibody together with docetaxel was not only accompanied by a smaller primary tumor volume compared to docetaxel alone, but also significantly reduced the occurrence and number of metastases. Conclusions: These data establish the proof-of-concept that blocking the exogenous action of S1P reduces intratumoral hypoxia and sensitizes to chemotherapy in prostate cancer animal model.

scholarly journals Targeted molecular-genetic imaging and ligand-directed therapy in aggressive variant prostate cancer

2016 ◽  
Vol 113 (45) ◽  
pp. 12786-12791 ◽  
Author(s):  
Fortunato Ferrara ◽  
Daniela I. Staquicini ◽  
Wouter H. P. Driessen ◽  
Sara D’Angelo ◽  
Andrey S. Dobroff ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Options ◽  
Molecular Genetic ◽  
Preclinical Model ◽  
Dual Function ◽  
Castration Resistant Prostate Cancer ◽  
Candidate Target ◽  
Aggressive Variant

Aggressive variant prostate cancers (AVPC) are a clinically defined group of tumors of heterogeneous morphologies, characterized by poor patient survival and for which limited diagnostic and treatment options are currently available. We show that the cell surface 78-kDa glucose-regulated protein (GRP78), a receptor that binds to phage-display-selected ligands, such as the SNTRVAP motif, is a candidate target in AVPC. We report the presence and accessibility of this receptor in clinical specimens from index patients. We also demonstrate that human AVPC cells displaying GRP78 on their surface could be effectively targeted both in vitro and in vivo by SNTRVAP, which also enabled specific delivery of siRNA species to tumor xenografts in mice. Finally, we evaluated ligand-directed strategies based on SNTRVAP-displaying adeno-associated virus/phage (AAVP) particles in mice bearing MDA-PCa-118b, a patient-derived xenograft (PDX) of castration-resistant prostate cancer bone metastasis that we exploited as a model of AVPC. For theranostic (a merging of the terms therapeutic and diagnostic) studies, GRP78-targeting AAVP particles served to deliver the human Herpes simplex virus thymidine kinase type-1 (HSVtk) gene, which has a dual function as a molecular-genetic sensor/reporter and a cell suicide-inducing transgene. We observed specific and simultaneous PET imaging and treatment of tumors in this preclinical model of AVPC. Our findings demonstrate the feasibility of GPR78-targeting, ligand-directed theranostics for translational applications in AVPC.

scholarly journals Effects of exercise training on tumor hypoxia and vascular function in the rodent preclinical orthotopic prostate cancer model

2013 ◽  
Vol 115 (12) ◽  
pp. 1846-1854 ◽  
Author(s):  
Danielle J. McCullough ◽  
Linda M.-D. Nguyen ◽  
Dietmar W. Siemann ◽  
Bradley J. Behnke
Keyword(s):  
Prostate Cancer ◽  
Exercise Training ◽  
Vascular Function ◽  
Contractile Function ◽  
Tumor Hypoxia ◽  
Ventral Prostate ◽  
Preclinical Model ◽  
Tumor Resistance ◽  
Resistance Artery

Regular physical exercise is considered to be an integral component of cancer care strategies. However, the effect of exercise training on tumor microvascular oxygenation, hypoxia, and vascular function, all of which can affect the tumor microenvironment, remains unknown. Using an orthotopic preclinical model of prostate cancer, we tested the hypotheses that, after exercise training, in the tumor, there would be an enhanced microvascular Po2, increased number of patent vessels, and reduced hypoxia. We also investigated tumor resistance artery contractile properties. Dunning R-3327 AT-1 tumor cells (104) were injected into the ventral prostate of 4–5-mo-old male Copenhagen or Nude rats, which were randomly assigned to tumor-bearing exercise trained (TB-Ex trained; n = 15; treadmill exercise for 5–7 wk) or sedentary groups (TB-Sedentary; n = 12). Phosphorescence quenching was used to measure tumor microvascular Po2, and Hoechst-33342 and EF-5 were used to measure patent vessels and tumor hypoxia, respectively. Tumor resistance artery function was assessed in vitro using the isolated microvessel technique. Compared with sedentary counterparts, tumor microvascular Po2 increased ∼100% after exercise training (TB-Sedentary, 6.0 ± 0.3 vs. TB-Ex Trained, 12.2 ± 1.0 mmHg, P < 0.05). Exercise training did not affect the number of patent vessels but did significantly reduce tumor hypoxia in the conscious, resting condition from 39 ± 12% of the tumor area in TB-Sedentary to 4 ± 1% in TB-Ex Trained. Exercise training did not affect vessel contractile function. These results demonstrate that after exercise training, there is a large increase in the driving force of O2 from the tumor microcirculation, which likely contributes to the considerable reduction in tumor hypoxia. These results suggest that exercise training can modulate the microenvironment of the tumor, such that a sustained reduction in tumor hypoxia occurs, which may lead to a less aggressive phenotype and improve patient prognosis.

Stromal and antitumor effects of BIBF 1120 (nintedanib) in a preclinical lung cancer model.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13563-e13563
Author(s):  
David E. Gerber ◽  
Bercin Kutluk Cenik ◽  
Katherine T Ostapoff ◽  
Rolf A. Brekken
Keyword(s):  
Lung Cancer ◽  
Microvessel Density ◽  
Single Agent ◽  
Preclinical Model ◽  
Antitumor Effects ◽  
Perfusion Studies ◽  
Significant Difference ◽  
Bibf 1120

e13563 Background: BIBF 1120 is an angiogenic receptor tyrosine kinase inhibitor that potently inhibits VEGFR, PDGFR and FGFR kinase activity in in vitro enzymatic assays. This study investigated the effect and mechanism of BIBF 1120, in vitro and in vivo, as a single agent and in combination with chemotherapy in preclinical models of lung cancer. Methods: Anti-tumor effects of BIBF 1120 in vitro were assessed using cell proliferation assays on five lung cancer lines (A549, Calu-3, Calu-6, H1993, H1703) with BIBF 1120 as a single agent and in combination with gemcitabine and cisplatin. To demonstrate anti-tumor activity in vivo, NOD/SCID mice bearing subcutaneous A549 grafts were treated daily with BIBF 1120 or BIBF 1120 plus chemotherapy. Perfusion studies were conducted using labeled dextrans. Ex vivo tumor tissues were assessed for architecture, microvessel density, pericyte coverage, proliferation, and apoptosis. Results: In vitro, BIBF 1120 did not show anti-proliferative effects at pharmacologically achievable concentrations (IC50>20μM) as a single agent; nor did it sensitize tumor cells to chemotherapy. However, BIBF 1120 inhibited primary tumor growth as a single agent and in combination therapy in subcutaneous endpoint studies with A549 xenografts. There was no significant difference in tumor architecture between BIBF 1120 and control-treated animals. Microvessel density (CD31,endomucin) and pericyte-covered vessels (NG2) were significantly decreased in BIBF 1120-treated animals compared to the control and chemotherapy only groups. Proliferation (phospho-histone 3) was decreased and apoptosis (cleaved caspase 3) was increased in BIBF 1120-treated animals compared to the control and chemotherapy only groups. Finally, BIBF 1120 significantly decreased perfusion in A549 xenografts. Conclusions: BIBF 1120 demonstrated potent anti-tumor and anti-angiogenic activity in a preclinical model of lung cancer. Because A549 was previously demonstrated to be an anti-VEGFR therapy resistant cell line, this study highlights the importance of FGFR and PDGFR pathways in the treatment of lung cancer.

scholarly journals Antioxidant and Neuroprotective Properties of Non-Centrifugal Cane Sugar and Other Sugarcane Derivatives in an In Vitro Induced Parkinson’s Model

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1040
Author(s):  
Javier Cifuentes ◽  
Vivian A. Salazar ◽  
Mónica Cuellar ◽  
María Claudia Castellanos ◽  
Jader Rodríguez ◽  
...  
Keyword(s):  
Bioactive Compounds ◽  
Thermal Processing ◽  
Biological Activities ◽  
Thermal Conditions ◽  
Cane Sugar ◽  
Neuroprotective Effects ◽  
Diphenyltetrazolium Bromide ◽  
Juice Extraction ◽  
Traditional Processing

Non-centrifugal cane sugar (NCS) is a traditional sweetener in most sugarcane regions of the world. In Colombia, this product has a socio-economic importance due to the extensive cultivation area and the high consumption rate per capita. NCS traditional processing involves consecutive stages of thermal processing that begin with juice extraction, clarification, evaporation, and finish with syrup crystallization into a solid commercial product, identified as NCS. Sugarcane is known to have a natural content of polyphenols, amino acids, vitamins, minerals, and complex sugars, some of which are reported as antioxidant and antiproliferative agents thought to be responsible for the product’s bioactive profile. There is evidence to suggest that traditional thermal processing to obtain NCS leads to a considerable decrease in the contents of these bioactive compounds, mainly due to uncontrolled process variables such as temperature. Accordingly, the aim of this study was to assess and compare the bioactivity of sugarcane (SC) derivatives produced under controlled thermal conditions versus the traditional method. To achieve this goal, we evaluated the cytotoxic, antioxidant, and neuroprotective effects of varying concentrations of SC derivatives in an in vitro induced Parkinson’s model. Results demonstrate non-cytotoxic activity on the cellular model by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and LDH assays, even at the highest tested concentration of 8 mg/mL, for all SC derivatives. The effect of SC derivatives on the induced oxidative stress model showed a biological reversion and recovering effect of the mitochondrial membrane potential and a halting of the progress into the early apoptosis phase. In conclusion, we demonstrated that the bioactive compounds present in SC derivatives obtained by a process under controlled temperature conditions are largely preserved, and even their biological activities are enhanced compared with SC derivatives obtained by the traditional thermal evaporation of SC-juice.

scholarly journals Comprehensive Analysis and Assessment of the Role of Major Bioactive Compounds Isolated from Justicia Adhatoda Leaves as Potent Antimycobacterial Agents

2022 ◽  
Author(s):  
Smita Mishra ◽  
Manisha Khatri ◽  
Varsha Mehra
Keyword(s):  
Bioactive Compounds ◽  
Ex Vivo ◽  
Scientific Evidence ◽  
Traditional Medicines ◽  
Ancient Times ◽  
Infectious Pathogen ◽  
Justicia Adhatoda ◽  
Global Population

Abstract Tuberculosis (TB) continues to be one of the world's leading causes of death by the infectious pathogen Mycobacterium tuberculosis, which infects one-third of the global population. The emergence of the COVID-19 pandemic made its spread rapid and the treatment task more daunting. With the havoc of infectious disease expansion, traditional medicines have triggered tremendous interest worldwide. However, less availability of scientific evidence still hinders its practical use. In the present study, we evaluated the potential of the traditional medicinal plant, Justicia adhatoda, which has been used to treat respiratory ailments since ancient times. We have successfully isolated and characterized several bioactive compounds viz- Vasicoline, Vasicolinone, Adhatodine, Adhavasine, Aniflorine, and Vasicinone from J. adhatoda plant leaves, including Vasicine as the principal compound, and showed their anti-tubercular activity on nutrient-starved Mycobacterium smegmatis and Mycobacterium bovis. The study also directs their in-vitro and ex-vivo antimycobacterial potential on THP1 macrophages with internalized Mycobacterium. Our study is one of its first kind, where we assessed the synergistic antimycobacterial effect of the isolated compounds with the first-line drug Isoniazid (INH). Their potential role in promoting phagolysosome fusion and apoptosis of M. bovis infected THP1 macrophages is further evaluated.

scholarly journals CYP24A1 Inhibition Enhances the Antitumor Activity of Calcitriol

Endocrinology ◽  
2010 ◽  
Vol 151 (9) ◽  
pp. 4301-4312 ◽  
Author(s):  
Josephia R. Muindi ◽  
Wei-Dong Yu ◽  
Yingyu Ma ◽  
Kristie L. Engler ◽  
Rui-Xian Kong ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Cytochrome P450 Enzymes ◽  
Antitumor Effects ◽  
Apoptosis Pathway ◽  
Antiproliferative Effects ◽  
Pc3 Cells ◽  
Apoptosis Inducing Factor

High systemic exposures to calcitriol are necessary for optimal antitumor effects. Human prostate cancer PC3 cells are insensitive to calcitriol treatment. Therefore, we investigated whether the inhibition of 24-hydroxylase (CYP24A1), the major calcitriol inactivating enzyme, by ketoconazole (KTZ) or RC2204 modulates calcitriol serum pharmacokinetics and biologic effects. Dexamethasone (Dex) was added to minimize calcitriol-induced hypercalcemia and as a steroid replacement for the KTZ inhibition of steroid biosynthesis cytochrome P450 enzymes. KTZ effectively inhibited time-dependent calcitriol-inducible CYP24A1 protein expression and enzyme activity in PC3 cells and C3H/HeJ mouse kidney tissues. Systemic calcitriol exposure area under the curve was higher in mice treated with a combination of calcitriol and KTZ than with calcitriol alone. KTZ and Dex synergistically potentiated calcitriol-mediated antiproliferative effects in PC3 cells in vitro; this effect was associated with enhanced apoptosis. After treatment with calcitriol and KTZ/Dex, although caspase-9 and caspase-3 were not activated and cytochrome c was not released by mitochondria, caspase-8 was activated and the truncated Bid protein level was increased. Translocation of apoptosis-inducing factor to the nucleus was observed, indicating a role of the apoptosis-inducing factor-mediated and caspase-independent apoptotic pathways. Calcitriol and KTZ/Dex combination suppressed the clonogenic survival and enhanced the growth inhibition observed with calcitriol alone in PC3 human prostate cancer xenograft mouse model. Our results show that the administration of calcitriol in combination with CYP24A1 inhibitor enhances antiproliferative effects, increases systemic calcitriol exposure, and promotes the activation of caspase-independent apoptosis pathway.

scholarly journals Brassicasterol from Edible Aquacultural Hippocampus abdominalis Exerts an Anti-Cancer Effect by Dual-Targeting AKT and AR Signaling in Prostate Cancer

Biomedicines ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 370
Author(s):  
Yinzhu Xu ◽  
Sooin Ryu ◽  
You-Kyung Lee ◽  
Hyo-Jeong Lee
Keyword(s):  
Prostate Cancer ◽  
Scientific Evidence ◽  
Specific Antigen ◽  
Bioactive Compound ◽  
Mass Spectrometry Data ◽  
Lncap Cells ◽  
Dual Targeting ◽  
Anti Cancer ◽  
Induced Apoptosis

In the Compendium of Materia Medica, seahorse (Hippocampus) is considered effective for the reinforcement of kidney and men’s health. However, the role of seahorse on human health lacks scientific evidence. Therefore, we evaluated the effect of seahorse on human prostate cancer using various in vitro methods and identified bioactive compound. Seahorse lipid extract (SHL) decreased androgen receptor (AR) and prostate-specific antigen (PSA) expression in dihydrotestosterone (DHT)-induced LNCaP cells of prostate cancer. Gas Chromatography (GC)-mass spectrometry data showed that brassicasterol was present in H. abdominalis. Brassicasterol downregulated the expression of AR and PSA in DHT-induced LNCaP cells. Brassicasterol induced apoptosis accompanied by sub-G1 phase arrest and inhibited migration in LNCaP cells. We confirmed that AKT and AR mediated the anti-cancer effect of brassicasterol using siRNA transfection. Brassicasterol exerts an anti-cancer effect in AR-independent cancer as well as in AR-dependent cells by AKT inhibiting. Our findings suggest that SHL has the anticancer potential via inhibition of AR and demonstrated that brassicasterol from H. abdominalis exerted an anti-cancer effect by dual-targeting AKT and AR signaling in prostate cancer.

scholarly journals Hemocyanins from Helix and Rapana Snails Exhibit in Vitro Antitumor Effects in Human Colorectal Adenocarcinoma

Biomedicines ◽  
2020 ◽  
Vol 8 (7) ◽  
pp. 194
Author(s):  
Ani Georgieva ◽  
Katerina Todorova ◽  
Ivan Iliev ◽  
Valeriya Dilcheva ◽  
Ivelin Vladov ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Mtt Assay ◽  
Biological Activities ◽  
Antitumor Effects ◽  
Α Subunit ◽  
Transmission Electron ◽  
Diphenyltetrazolium Bromide ◽  
Potential Applications ◽  
Ht 29

Hemocyanins are oxygen-transporting glycoproteins in the hemolymph of arthropods and mollusks that attract scientific interest with their diverse biological activities and potential applications in pharmacy and medicine. The aim of the present study was to assess the in vitro antitumor activity of hemocyanins isolated from marine snail Rapana venosa (RvH) and garden snails Helix lucorum (HlH) and Helix aspersa (HaH), as well the mucus of H. aspersa snails, in the HT-29 human colorectal carcinoma cell line. The effects of the hemocyanins on the cell viability and proliferation were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the alterations in the tumor cell morphology were examined by fluorescent and transmission electron microscopy. The results of the MTT assay showed that the mucus and α-subunit of hemocyanin from the snail H. aspersa had the most significant antiproliferative activity of the tested samples. Cytomorphological analysis revealed that the observed antitumor effects were associated with induction of apoptosis in the tumor cells. The presented data indicate that hemocyanins and mucus from H. aspersa have an antineoplastic activity and potential for development of novel therapeutics for treatment of colorectal carcinoma.

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