Ethanolic Extract of Algerian Propolis and Galangin Decreased Murine Melanoma Tumor Progression in Mice

2016 ◽  
Vol 16 (9) ◽  
pp. 1172-1183 ◽  
Author(s):  
Lamia Benguedouar ◽  
Mesbah Lahouel ◽  
Sophie C. Gangloff ◽  
Anne Durlach ◽  
Florent Grange ◽  
...  
Keyword(s):  
Tumour Growth ◽  
Tumour Progression ◽  
Ethanolic Extract ◽  
Complementary Therapy ◽  
Melanoma Cells ◽  
Biological Properties ◽  
Therapeutic Treatment ◽  
Melanoma Tumor ◽  
Ki 67

Melanoma is the more dangerous skin cancer, and metastatic melanoma still carries poor prognosis. Despite recent therapeutic advances, prolonged survival remains rare and research is still required. Propolis extracts from many countries have attracted a great deal of attention for their biological properties. We here investigated the ability of an ethanolic extract of Algerian propolis (EEP) to control melanoma tumour growth when given to mice bearing B16F1melanoma tumour either as preventive or as therapeutic treatment. EEP given after tumour occurrence increased mice survival (+30%) and reduced tumour growth (-75%). This was associated with a decrease of the Mitotic Index (-75%) and of Ki-67 (-50%) expression. When given either before or both before and after tumour occurrence, EEP reduced tumour growth but without prolonging mice life. Isolation of B16F1 melanoma cells from resected tumour showed that preventive and curative EEP treatments reduced invasiveness by 55% and 40% respectively compared to control. Galangin, one of the most abundant flavonoids in propolis, significantly reduced the number of melanoma cells in vitro and induced autophagy/apoptosis dose dependently. In conclusion, we showed that EEP reduced melanoma tumour progression/dissemination and could extend mice lifespan when used as therapeutic treatment. Then, EEP may help patients with melanoma when used as a complementary therapy to classical treatment for which autophagy is not contraindicated.

scholarly journals Treatment with Uncaria tomentosa Promotes Apoptosis in B16-BL6 Mouse Melanoma Cells and Inhibits the Growth of B16-BL6 Tumours

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1066
Author(s):  
Ali Zari ◽  
Hajer Alfarteesh ◽  
Carly Buckner ◽  
Robert Lafrenie
Keyword(s):  
Tumour Size ◽  
Melanoma Cells ◽  
Tunel Staining ◽  
Aqueous Extracts ◽  
Ki 67 ◽  
Uncaria Tomentosa ◽  
Mouse Melanoma ◽  
Anti Cancer

Uncaria tomentosa is a medicinal plant native to Peru that has been traditionally used in the treatment of various inflammatory disorders. In this study, the effectiveness of U. tomentosa as an anti-cancer agent was assessed using the growth and survival of B16-BL6 mouse melanoma cells. B16-BL6 cell cultures treated with both ethanol and phosphate-buffered saline (PBS) extracts of U. tomentosa displayed up to 80% lower levels of growth and increased apoptosis compared to vehicle controls. Treatment with ethanolic extracts of Uncaria tomentosa were much more effective than treatment with aqueous extracts. U. tomentosa was also shown to inhibit B16-BL6 cell growth in C57/bl mice in vivo. Mice injected with both the ethanolic and aqueous extracts of U. tomentosa showed a 59 ± 13% decrease in B16-BL6 tumour weight and a 40 ± 9% decrease in tumour size. Histochemical analysis of the B16-BL6 tumours showed a strong reduction in the Ki-67 cell proliferation marker in U. tomentosa-treated mice and a small, but insignificant increase in terminal transferase dUTP nick labelling (TUNEL) staining. Furthermore, U. tomentosa extracts reduced angiogenic markers and reduced the infiltration of T cells into the tumours. Collectively, the results in this study concluded that U. tomentosa has potent anti-cancer activity that significantly inhibited cancer cells in vitro and in vivo.

scholarly journals IN VITRO ANTHELMINTIC AND ANTI-AMYLASE PROPERTIES OF GARCINIA PEDUNCULATA ROXB. ETHANOLIC EXTRACT

2016 ◽  
Vol 9 (1) ◽  
pp. 189
Author(s):  
Pinky Sarmah ◽  
Nako Kobing ◽  
Jyotchna Gogoi ◽  
Ananta Madhab Dutta
Keyword(s):  
Anthelmintic Activity ◽  
Ethanolic Extract ◽  
Ethanol Extract ◽  
Biological Properties ◽  
Death Time ◽  
Control Sets ◽  
Point Analysis ◽  
Soxhlet Apparatus ◽  
And Control

<p><strong>Objective</strong>:<strong> </strong>The present study aims to investigate <em>in vitro</em> anthelmintic and anti-amylase properties of the ethanolic fruit extract of <em>Garcinia pedunculata</em>.</p><p><strong>Methods</strong>:<strong> </strong>For the study, mature fruits of <em>G. pedunculata</em> were collected from local markets during April-May. Fleshy pericarps of fruits were chopped into small pieces, dried and extracted by using a Soxhlet apparatus. Ethanol extract of <em>G. pedunculata</em> was used for evaluation of <em>in vitro</em> anthelmintic and anti-amylase activities. <em>In vitro</em> anthelmintic activity was evaluated in animal models, <em>Pheretima posthuma</em>, an earthworm species. <em>In vitro</em> anti-amylase activity was evaluated by using zymographic, achromic point analysis (Starch-Iodine method) and spectrophotometric method [Di Nitro Salicylic acid (DNS)–Maltose method].</p><p><strong>Results</strong>:<strong> </strong>Ethanolic extract of <em>G. pedunculata</em> showed anthelmintic activity at a concentration of 75 mg/ml, paralysis and death timing was reported at 0.62±0.26 min and 1.42±0.07 min, respectively. The reference standard (Albendazole) showed paralysis time: 2.13±0.28 min and death time: 5.12±0.29 min. In the anti-amylase study, a zymographic density analysis of <em>G. pedunculata</em> showed significant variation in band intensity as compared to Starch–Iodine achromic point analysis and DNS–Maltose method. A concentration of 1.5 mg/ml of extract showed inhibition of amylase: 67.65±1.53 % as compared to other concentrations and control sets.</p><strong>Conclusion</strong>:<strong> </strong>It could be concluded that ethanolic extract of <em>G. pedunculata</em>has biological properties which could be utilised in medicine by characterising its bioactive components.<p> </p>

Effect of mebendazole on melanoma xenograft growth through targeting of bcl-2

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9075-9075
Author(s):  
N. A. Doudican ◽  
R. Pennell ◽  
T. Tu ◽  
L. Liebes ◽  
A. Pavlick ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Xenograft Model ◽  
Melanoma Cells ◽  
High Dose ◽  
Tumor Diameter ◽  
Proliferating Cells ◽  
Melanoma Tumor ◽  
Mouse Xenograft Model ◽  
Melanoma Growth

9075 Background: Defects in apoptosis are thought to contribute to melanoma chemoresistance, making the anti-apoptotic protein Bcl-2 an attractive therapeutic target. We identified mebendazole (MBZ), a microtubule binding agent, as an inducer of melanoma cytotoxicity via a Bcl-2 dependent mechanism in vitro (Mol Cancer Res, Aug 2008). In the present study, we assessed the effect of MBZ on human melanoma tumor growth and progression in a mouse xenograft model and compared the ability of MBZ to inhibit growth of cultured melanoma cells to that of oblimersen (OBL), an antisense drug targeting Bcl-2. Methods: Growth of human M-14 melanoma xenografts in mice administered MBZ orally at doses from 0.1 to 2 mg were compared to tumor growth in mice receiving 100mg/kg intraperitoneal temozolomide (TMZ) or vehicle alone. Tumor diameter, volume, histopathology, and immunohistochemical staining of caspase 3 and Ki67 were assessed. Bcl-2 phosphorylation was determined by immunoblotting. MBZ and OBL-induced melanoma growth inhibition was analyzed by MTT assay. Results: Anti-melanoma effects of MBZ were dose- dependent up to 1 mg which displayed a 72% reduction in tumor volume compared to vehicle treated mice. This reduction in volume was accompanied by a 46% decrease in proliferating cells and an 81% increase in apoptotic cells. Moreover, 1 mg MBZ inhibited tumor growth as effectively as high dose TMZ, the current melanoma standard of care. Orally administered MBZ treatment resulted in Bcl-2 phosphorylation in vivo, further confirming its mechanism of action. MBZ inhibited growth of melanoma cells in culture more effectively than OBL with GI50 values of 0.32 uM and 7.45 uM, respectively. Conclusions: MBZ safely and effectively inhibits melanoma growth and progression in a xenograft model. A phase II clinical trial investigating MBZ's utility as adjuvant therapy in patients with stage IV, resected melanoma is planned. No significant financial relationships to disclose.

scholarly journals Antioxidant Extracts of Three Russula Genus Species Express Diverse Biological Activity

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4336
Author(s):  
Marina Kostić ◽  
Marija Ivanov ◽  
Ângela Fernandes ◽  
José Pinela ◽  
Ricardo C. Calhelha ◽  
...  
Keyword(s):  
Ethanolic Extract ◽  
Thiobarbituric Acid ◽  
Biological Properties ◽  
Free Sugar ◽  
Cytotoxic Activities ◽  
Cinnamic Acids ◽  
Mushroom Species ◽  
Oxidative Hemolysis ◽  
Diverse Biological Activity

This study explored the biological properties of three wild growing Russula species (R. integra, R. rosea, R. nigricans) from Serbia. Compositional features and antioxidant, antibacterial, antibiofilm, and cytotoxic activities were analyzed. The studied mushroom species were identified as being rich sources of carbohydrates and of low caloric value. Mannitol was the most abundant free sugar and quinic and malic acids the major organic acids detected. The four tocopherol isoforms were found, and polyunsaturated fatty acids were the predominant fat constituents. Regarding phenolic compounds, P-hydroxybenzoic and cinnamic acids were identified in the prepared methanolic and ethanolic extracts, which displayed antioxidant activity through the inhibition of thiobarbituric acid reactive substances (TBARS) formation and oxidative hemolysis; the highest activity was attributed to the R. nigricans ethanolic extract. This is the first report on the antibacterial and antibiofilm potential of the studied species, with the most promising activity observed towards Streptococcus spp. (0.20–0.78 mg/mL as the minimal inhibitory concentration, MIC). The most promising cytotoxic effect was caused by the R. integra methanolic extract on non-small cell lung cancer cells (NCI-H460). Therefore, due to the observed in vitro bioactive properties, the studied mushrooms arise as a source of functional ingredients with potential to be used in novel nutraceutical and drug formulations, which can be used in the treatment of various diseases and health conditions.

scholarly journals Investigation of the effects of mTOR inhibitors rapamycin and everolimus in combination with carboplatin on canine malignant melanoma cells

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Sarah Bernard ◽  
Andrew C. Poon ◽  
Peyton M. Tam ◽  
Anthony J. Mutsaers
Keyword(s):  
Malignant Melanoma ◽  
Cell Viability ◽  
Cell Lines ◽  
Tumour Progression ◽  
Mtor Inhibitors ◽  
Melanoma Cells ◽  
Combination Drug ◽  
Mechanistic Investigation ◽  
Canine Melanoma

Abstract Background Malignant melanoma in dogs is considered to be largely resistant to conventional chemotherapy, although responses to carboplatin have been documented. Invasion and early metastasis are common features of certain melanoma subtypes that contribute to tumour progression despite aggressive local and systemic therapy. Upregulation of the PI3K/AKT/mTOR pathway has been observed in canine malignant melanoma and may represent a potential target for therapy. Rapamycin (sirolimus) and everolimus are commercially available small molecule inhibitors that target mTOR and therefore may have anticancer activity in canine melanoma. It was hypothesized that there is synergism between rapamycin or everolimus and platinum chemotherapy, and that combination drug treatment would inhibit target/downstream proteins involved in cell viability/proliferation and increase cell death in canine melanoma cells. It was further hypothesized that rapamycin or everolimus would impact metabolism by reducing glycolysis in these cells. Four canine melanoma cell lines were treated in vitro with rapamycin and everolimus as sole treatment or combined with carboplatin. Cell viability, apoptosis, target modulation, and glycolytic metabolism were evaluated by crystal violet colourimetric assay, Annexin V/PI flow cytometry, western blotting, and Seahorse bioanalyzer, respectively. Results When combined with carboplatin chemotherapy, rapamycin or everolimus treatment was overall synergistic in reducing cell viability. Carboplatin-induced apoptosis was noted at 72 h after treatment compared to the vehicle control. Levels of phosphorylated mTOR were reduced by rapamycin and everolimus in all four cell lines, but activation of the downstream protein p70S6K was not consistently reduced by treatment in two of the cell lines. Both mTOR inhibitors decreased the extracellular acidification rate of canine melanoma cells, indicating reduced cancer cell glycolytic activity. Conclusions Inhibition of mTOR by rapalogs, such as rapamycin and everolimus combined with carboplatin chemotherapy may have activity in canine melanoma. Future mechanistic investigation is warranted, including in vivo assessment of this combination therapy.

scholarly journals Polyvinyl Alcohol Carbazate as a Polymer-Based Antitumoral Agent

2021 ◽  
Vol 10 ◽  
Author(s):  
Felix Sellberg ◽  
Robin Fröbom ◽  
Christian Binder ◽  
Erik Berglund ◽  
David Berglund
Keyword(s):  
Mouse Model ◽  
Polyvinyl Alcohol ◽  
Growth Inhibition ◽  
Unmet Need ◽  
Biological Properties ◽  
Tumor Growth Inhibition ◽  
Athymic Mice ◽  
Ki 67

Development of treatment resistance is a major concern during treatment of cancer, and there is an unmet need for therapeutic strategies with novel modes of action. Polyvinyl alcohol carbazate (PVAC) is a polymer compound with unique biological properties. Herein, we describe the antitumoral effects of PVAC. Three well-established cell lines GIST-T1, B16.F10, and A375 were used to determine the in vitro antitumoral effects of PVAC. Assessments included light microscopy, cell viability, cell cycle, and apoptosis assays. In vivo treatment safety and efficacy were characterized in one immunocompetent (B16.F10) mouse model and one athymic nude (MDA-MB-231) mouse model. Excised tumors were measured, weighed, stained for Ki-67, CD3, and histopathologically evaluated. Intact PVAC expressed a non-linear dose-response antitumoral effect in vitro, whereas its separate components, PVA and carbazate, did not display antitumoral effects alone. In vivo, PVAC induced a significant intratumoral CD3+ T-cell recruitment in immunocompetent mice (B16.F10), which was associated with tumor growth inhibition. Although growth inhibition was not significant in athymic mice (MDA-MB-231), histopathological evaluation detected an increase in stromal tissue and leukocyte infiltration. In conclusion, we present evidence for PVAC antitumoral effects both in vitro and in vivo. The mode of action was not elucidated in vitro, but a potential mechanism of in vivo activity was observed, characterized by an increase of immune cells into both immunocompetent and athymic mice. This finding warrants further study to validate its possible role as an immunomodulatory polymeric agent.

scholarly journals The Antifungal Mechanism of Isoxanthohumol from Humulus lupulus Linn.

2021 ◽  
Vol 22 (19) ◽  
pp. 10853
Author(s):  
Yin-Fang Yan ◽  
Tian-Lin Wu ◽  
Sha-Sha Du ◽  
Zheng-Rong Wu ◽  
Yong-Mei Hu ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Ethanolic Extract ◽  
Biological Properties ◽  
Membrane Lipid ◽  
Phytopathogenic Fungi ◽  
Humulus Lupulus ◽  
Edible Plant ◽  
Antifungal Mechanism

Humulus lupulus Linn. is a traditional medicinal and edible plant with several biological properties. The aims of this work were: (1) to evaluate the in vitro antifungal activity of H. lupulus ethanolic extract; (2) to study the in vitro and in vivo antifungal activity of isoxanthohumol, an isoprene flavonoid from H. lupulus, against Botrytis cinerea; and (3) to explore the antifungal mechanism of isoxanthohumol on B. cinerea. The present data revealed that the ethanolic extract of H. lupulus exhibited moderate antifungal activity against the five tested phytopathogenic fungi in vitro, and isoxanthohumol showed highly significant antifungal activity against B. cinerea, with an EC50 value of 4.32 µg/mL. Meanwhile, it exhibited moderate to excellent protective and curative efficacies in vivo. The results of morphologic observation, RNA-seq, and physiological indicators revealed that the antifungal mechanism of isoxanthohumol is mainly related to metabolism; it affected the carbohydrate metabolic process, destroyed the tricarboxylic acid (TCA) cycle, and hindered the generation of ATP by inhibiting respiration. Further studies indicated that isoxanthohumol caused membrane lipid peroxidation, thus accelerating the death of B. cinerea. This study demonstrates that isoxanthohumol can be used as a potential botanical fungicide for the management of phytopathogenic fungi.

scholarly journals The mechanosensitive TRPV2 calcium channel controls melanoma invasiveness and metastatic potential.

2021 ◽  
Author(s):  
Kenji F Shoji ◽  
Elsa Bayet ◽  
Dahiana Le Devedec ◽  
Aude Mallavialle ◽  
Severine Marionneau-lambot ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Metastatic Melanoma ◽  
Metastatic Potential ◽  
Melanoma Cells ◽  
Melanoma Tumor ◽  
Advanced Malignancy ◽  
In Vitro Motility ◽  
Cytoskeleton Remodeling

Discovery of therapeutic targets against metastasis is of primary importance since being the main cause of cancer-related death. Deregulation of calcium homeostasis has been involved in numerous cellular metastatic behaviors, although the molecular determinants supporting these processes remain often unclear. Here, we showed that the expression of the plasma membrane TRPV2 calcium channel is a prominent feature in melanoma progression and dissemination. In fact, TRPV2 activity was sufficient to confer an invasive phenotype to non-invasive melanoma cells. Conversely, the invasive and migratory potential of highly metastatic melanoma cells was abolished upon TRPV2 silencing. Mechanistically, TRPV2 supports melanoma cells aggressiveness by being a new regulator of the calpain-dependent maturation of focal adhesion, and actin cytoskeleton remodeling. Finally, TRPV2 overexpression is a marker of advanced malignancy and bad prognosis in human melanoma tumor samples. Altogether, TRPV2-induced Ca2+ signaling orchestrates in vitro motility and invasiveness of melanoma cells, as well as in vivo metastatic melanoma tumors dissemination.

scholarly journals Cisplatin-Induced Giant Cells Formation Is Involved in Chemoresistance of Melanoma Cells

2020 ◽  
Vol 21 (21) ◽  
pp. 7892
Author(s):  
Chien-Hui Weng ◽  
Chieh-Shan Wu ◽  
Jian-Ching Wu ◽  
Mei-Lang Kung ◽  
Ming-Hsiu Wu ◽  
...  
Keyword(s):  
Multiple Drug Resistance ◽  
Giant Cells ◽  
Melanoma Cells ◽  
Cell Diameter ◽  
Multiple Drug ◽  
Stem Cell Markers ◽  
Ki 67 ◽  
Cancer Stem Cell Markers

Melanoma is notoriously resistant to current cancer therapy. However, the chemoresistance mechanism of melanoma remains unclear. The present study unveiled that chemotherapy drug cisplatin induced the formation of giant cells, which exhibited enlargement in cell diameter and nucleus in mice and human melanoma cells. Giant cells were positive with melanoma maker S100 and cancer stem cell markers including ABCB5 and CD133 in vitro and in vivo. Moreover, giant cells retained the mitotic ability with expression of proliferation marker Ki-67 and exhibited multiple drug resistance to doxorubicin and actinomycin D. The mitochondria genesis/activities and cellular ATP level were significantly elevated in giant cells, implicating the demand for energy supply. Application of metabolic blockers such as sodium azide or 2-deoxy glucose abolished the cisplatin-induced giant cells formation and expression of cancer stemness markers. The present study unveils a novel chemoresistance mechanism of melanoma cells via size alteration and the anti-neoplastic strategy by targeting giant cells.

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