Decitabine, independent of apoptosis, exerts its cytotoxic effects on cell growth in melanoma cells

2011 ◽  
Vol 32 (3) ◽  
pp. 423-429 ◽  
Author(s):  
Qian-Ying Liu ◽  
Da-Wei Chen ◽  
Li-Ping Xie ◽  
Rong-Qing Zhang ◽  
Hong-Zhong Wang
Keyword(s):  
Cell Growth ◽  
Melanoma Cells ◽  
Cytotoxic Effects

Photocatalytic and Cytotoxic Effects of Nitrogen-Doped TiO2 Nanoparticles on Melanoma Cells

2018 ◽  
Vol 18 (5) ◽  
pp. 3722-3728 ◽  
Author(s):  
Pedro Faria Zeni ◽  
Disley Prates Dos Santos ◽  
Rafael Renatino Canevarolo ◽  
José Andrés Yunes ◽  
Francine Ferreira Padilha ◽  
...  
Keyword(s):  
Tio2 Nanoparticles ◽  
Melanoma Cells ◽  
Cytotoxic Effects ◽  
Doped Tio2 ◽  
Nitrogen Doped

scholarly journals Fibroblasts Protect Melanoma Cells from the Cytotoxic Effects of Doxorubicin

2014 ◽  
Vol 20 (17-18) ◽  
pp. 2412-2421 ◽  
Author(s):  
Manoela Tiago ◽  
Edson Mendes de Oliveira ◽  
Carla Abdo Brohem ◽  
Paula Comune Pennacchi ◽  
Rafael Duarte Paes ◽  
...  
Keyword(s):  
Melanoma Cells ◽  
Cytotoxic Effects

scholarly journals Modulation of cell growth and cisplatin sensitivity by membrane γ-glutamyltransferase in melanoma cells

2006 ◽  
Vol 42 (15) ◽  
pp. 2623-2630 ◽  
Author(s):  
Maria Franzini ◽  
Alessandro Corti ◽  
Evelina Lorenzini ◽  
Aldo Paolicchi ◽  
Alfonso Pompella ◽  
...  
Keyword(s):  
Cell Growth ◽  
Melanoma Cells ◽  
Cisplatin Sensitivity

scholarly journals Cinobufagin Suppresses Melanoma Cell Growth by Inhibiting LEF1

2020 ◽  
Vol 21 (18) ◽  
pp. 6706
Author(s):  
Geon-Hee Kim ◽  
Xue-Quan Fang ◽  
Woo-Jin Lim ◽  
Jooho Park ◽  
Tae-Bong Kang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Melanoma Cell ◽  
Transcriptional Activity ◽  
Melanoma Cells ◽  
Lung Cancer Cells ◽  
Luciferase Assay ◽  
Dependent Manner

Constitutive activation of the β-catenin dependent canonical Wnt signaling pathway, which enhances tumor growth and progression in multiple types of cancer, is commonly observed in melanoma. LEF1 activates β-catenin/TCF4 transcriptional activity, promoting tumor growth and progression. Although several reports have shown that LEF1 is highly expressed in melanoma, the functional role of LEF1 in melanoma growth is not fully understood. While A375, A2058, and G361 melanoma cells exhibit abnormally high LEF1 expression, lung cancer cells express lower LEF1 levels. A luciferase assay-based high throughput screening (HTS) with a natural compound library showed that cinobufagin suppressed β-catenin/TCF4 transcriptional activity by inhibiting LEF1 expression. Cinobufagin decreases LEF1 expression in a dose-dependent manner and Wnt/β-catenin target genes such as Axin-2, cyclin D1, and c-Myc in melanoma cell lines. Cinobufagin sensitively attenuates cell viability and induces apoptosis in LEF1 expressing melanoma cells compared to LEF1-low expressing lung cancer cells. In addition, ectopic LEF1 expression is sufficient to attenuate cinobufagin-induced apoptosis and cell growth retardation in melanoma cells. Thus, we suggest that cinobufagin is a potential anti-melanoma drug that suppresses tumor-promoting Wnt/β-catenin signaling via LEF1 inhibition.

An Acidic Milieu Created In Myeloma-Osteoclast Interaction Enhances Tumor Growth, but Triggers Anti-Myeloma Activity of Reveromycin A, a Novel Anti-Resorptive Agent

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 454-454
Author(s):  
Keiichiro Watanabe ◽  
Masahiro Abe ◽  
Qu Cui ◽  
Makoto Kawatani ◽  
Masahiro Hiasa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Death ◽  
Cell Growth ◽  
Bone Marrow Cells ◽  
Lactate Production ◽  
Bone Destruction ◽  
Cytotoxic Effects ◽  
Acidic Microenvironment ◽  
Pit Formation ◽  
Rabbit Bone

Abstract Abstract 454 Multiple myeloma (MM) develops and expands in the bone marrow, and causes devastating bone destruction by enhancing osteoclastic bone resorption in their close vicinity. In MM bone lesions, thus induced osteoclasts (OCs) in turn enhance MM cell growth and survival, thereby forming a vicious cycle between the progression of bone destruction and MM tumor expansion. Such cellular interactions create an acidic milieu not only through acids produced by OCs but also through a large amount of lactate by proliferating tumor cells (Warburg effect). Reveromycin A (RM-A), a small microbial metabolite, preferentially induces cellular apoptosis in an acidic milieu, and draws considerable attention as a novel anti-resorptive agent. In the present study, we explored whether an acidic condition induced by MM-OC interaction affects MM expansion and whether RM-A targets not only OCs but also such an acidic microenvironment to regress tumor expansion in MM. INA6 and RPMI8226 MM cells potently enhanced osteoclastogenesis and osteoclastic pit formation when cocultured with rabbit bone marrow cells on bone slices. Notably, large multinucleated OCs were almost completely disappeared and pit formation on bone slices was abolished upon the treatment with RM-A at concentrations as low as 100nM. The cocultures with rabbit bone marrow cells stimulated INA6 MM cell growth; RM-A at 1microM was however able to substantially decrease the MM cell viability in the cocultures after 12 hours, although RM-A at this concentration did not affect MM cell growth when MM cells were cultured alone at pH7.4. The suppression of INA6 MM cell viability by RM-A was obviously more potent than that under bisphosphonate treatment in which mature OCs and pits on bone slices similarly decreased in number, suggesting that the anti-MM effects of RM-A is not merely due to depletion of mature OCs. Blockade of acid release by the proton pump inhibitor concanamycin A abolished such RM-A effects. Because an acidic microenvironment increases cell permeability of RM-A to cause apoptosis, it is plausible that a highly acidic milieu created by OC-MM interaction allows RM-A to act on nearby MM cells as well as OCs. In order to clarify a role of tumor acidity in RM-A-triggered cell death, we examined the effects of RM-A on MM cell growth upon acidification with lactic acid. When lactic acid was added to media to adjust their pH to be 7.0 and 6.75, the growth of INA6 and RPMI8226 MM cells was enhanced up to 150 and 120%, respectively, after 24 hours compared to that at pH7.4. However, RM-A at 1microM induced cell death in these MM cells at pH7.0 (60-70% reduction of alive MM cells compared to those at pH7.4) and at pH6.75 (>90%), suggesting cytocidal effects of RM-A on lactate-producing MM cells densely proliferated in an acidic milieu. Because metoformin, anti-diabetic agent, up-regulates lactate production through stimulation of glycolysis, we next examined the effects of RM-A on MM cells in combination with metoformin. Metoformin dose-dependently enhanced lactate production by MM cells to decrease pH in their culture media over time; RM-A at 1microM showed potent cytotoxic effects on MM cells upon 24-hour preceded treatment with metoformin at 5 mM even when MM cells were started to be cultured at pH7.4, suggesting induction of anti-MM activity of RM-A with metoformin. Finally, in vivo RM-A effects were studied using INA6 MM cell-bearing SCID-rab mice. We injected RM-A sc at 4mg/kg twice daily for 18 days to the mice after confirming MM cell growth at 4 weeks after the MM cell inoculation. The RM-A treatment substantially decreased osteolytic lesions in X-ray and microCT images and MM tumor area in bone sections along with a reduction of INA6 cell-derived human soluble IL-6 receptor levels in mouse sera as a marker of MM tumor burden. These results collectively suggest that acidic microenvironment produced by MM-OC interaction enhances MM tumor progression but can trigger cytotoxic effects of RM-A on MM cells besides acid-producing OCs. RM-A may become a candidate for a novel therapeutic agent against MM with extensive bone resorption. Disclosures: No relevant conflicts of interest to declare.

The Combination of the Novel Syk Inhibitor TAK659 with Decitabine Exerts Synergistic Cytotoxic Effects Against FLT3/ITD Mutated Acute Myeloid Leukemia Cells

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4928-4928
Author(s):  
Edwin Stage ◽  
Magdalena Czader ◽  
Heather O'Leary ◽  
H. Scott Boswell ◽  
Larry D. Cripe ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Stromal Cells ◽  
Single Agent ◽  
The Novel ◽  
Cytotoxic Effects ◽  
Syk Inhibitor ◽  
Induction Of Apoptosis ◽  
Dose Dependent ◽  
Agent Treatment

Abstract Background: Effective treatment regimens for FLT3/ITD+ AML patients are lacking. Recent data on the effects of FLT3 tyrosine kinase inhibition showed promising clinical activity, but outcomes have been stunted by drug resistance. Targeting additional signaling pathways besides FLT3 might therefore offer therapeutic benefit. Spleen tyrosine kinase (syk) is frequently overexpressed and constitutively activated in primary AML FLT3/ITD+ blasts. Pharmacologic inhibition of syk has been associated with antileukemic potential, consisting of inhibition of cell growth and induction of differentiation in AML cells. Hypomethylating agents (DNMTis) such as Decitabine (DEC) have emerged as attractive agents in the treatment of AML, partially due to their proapoptotic and differentiation inducing effects. There is a strong rationale for combining FLT3- and syk- inhibitors with DNMTis for FLT3/ITD+ AML. Here, we investigated whether the antileukemic effects of the novel, dual FLT3/syk inhibitor TAK659 (TAK) can be enhanced by the co-administration of DEC. Methods: Molm14 (M14) cells were incubated in culture medium in the presence and absence of stromal cells (MS5) for 72 hours. TAK or DEC was added in single agent or combined mode at the indicated concentrations. After the incubation period, cell growth was determined by MTT assays. Apoptosis, autophagy and cell cycle status were assessed by FACS analysis. FLT3- and syk- phosphorylation levels were detected by western blotting. Differentiation was assessed by morphology. A combination index (CI) was calculated using Calcusyn Software. Results: TAK exerted dose dependent effects against M14 cells. However, the presence of stromal cells significantly blunted TAK mediated cytotoxicity (50nM: 61.9±1.3% [off stroma] vs. 10.9±3.1% [on stroma], p<.001; 500nM: 91.2±0.5% [off stroma] vs. 17.4±2.5% [on stroma], p<.001, n=3-9; IC50: 40.6nM [off stroma] vs. 3.9µM [on stroma]). Although less marked when stroma was present, TAK combined with DEC yielded synergistically enhanced growth inhibition (off stroma: 50.2±3.9% [TAK659 50nM], 58.1±3.0% [DEC 1µM], 76.7±3.1% [TAK659 50nM+DEC 1µM; CI=0.77]; on stroma: 9.5±3.0%[TAK659 50nM], 42.9±3.1% [DEC1µM], 57.0±5.2%[TAK659 50nM+DEC 1µM; CI=0.62]) compared to single agent treatment (off stroma: p<.001 vs. TAK, p< .001 vs. DEC, on stroma: p<.001 vs.TAK, p=.03 vs. DEC, n=3). In line with these findings, combined treatment yielded greater levels of FLT3- and syk- dephosphorylation compared to single agent treatment both when stroma was present and absent. When compared to untreated controls (11.6±0.7%), Annexin V/PI staining (n=3) showed that induction of apoptosis was increased with TAK (18.9±3.9%; p=NS), DEC (39.2±4.8%; p<.01), and greatest when the two drugs were combined (44.2±6.7%; p<.01) in the absence stoma. In the presence of stroma, single agent DEC, and when combined with TAK, increased the fraction of apoptotic cells by up to two fold whereas TAK did not induce any meaningful apoptosis. Consistent with the induction of cell death, cell cycle analysis demonstrated the greatest increase in subG0 phase when TAK and DEC were combined. Both in the presence and absence of stroma, autophagic flux was increased when M14 cells were treated with DEC, and when DEC was combined with TAK whereas no difference was observed with TAK alone. The combination of TAK and DEC led to changes consistent with differentiation, as shown by more abundant cytoplasm and nuclei with deep indentations, folds and lobulation compared to untreated cells. DEC treated cells also showed signs of differentiation although these changes were less marked. No evidence of differentiation was observed in M14 cells when treated with TAK alone. Conclusions: 1. Stroma conferred protective effects against all treatments. 2. TAK exerted dose dependent cytotoxicity against M14 cells in the nanomolar to low micromolar range in the absence and presence of stroma, respectively. 3. The cytotoxic effects of TAK were enhanced when TAK was combined with DEC. 4. The antileukemic effects of TAK combined with DEC are multifaceted and include inhibition of cell growth, induction of apoptosis, autophagy and differentiation. 5. The combination of TAK and DEC represents a potentially important novel approach for FLT3/ITD+ AML patients. 6. Clinical trials incorporating syk-inhibitors into standard AML treatment protocols are currently under way. Disclosures Dos Santos: Amgen: Employment.

scholarly journals ROS production induced by BRAF inhibitor treatment rewires metabolic processes affecting cell growth of melanoma cells

2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Giulia Cesi ◽  
Geoffroy Walbrecq ◽  
Andreas Zimmer ◽  
Stephanie Kreis ◽  
Claude Haan
Keyword(s):  
Cell Growth ◽  
Braf Inhibitor ◽  
Melanoma Cells ◽  
Ros Production ◽  
Metabolic Processes ◽  
Inhibitor Treatment

scholarly journals Ceramide generation as a novel biological mechanism for chemo-preventive and cytotoxic effects of hesperidin on HT-144 melanoma cells

2018 ◽  
Vol 7 (4) ◽  
pp. 640-645 ◽  
Author(s):  
Mahdi Mashhadi Akbar Boojar ◽  
Masoud Mashhadi Akbar Boojar ◽  
Sepide Golmohammad ◽  
Mojtaba Nikkhah Yazdi
Keyword(s):  
Melanoma Cells ◽  
Biological Mechanism ◽  
Cytotoxic Effects ◽  
Ceramide Generation
Sign in / Sign up

Export Citation Format

Share Document