scholarly journals Selective and Irreversible Induction of Necroptotic Cell Death in Lung Tumorspheres by Short-Term Exposure to Verapamil in Combination with Sorafenib

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Juan Sebastian Yakisich ◽  
Yogesh Kulkarni ◽  
Neelam Azad ◽  
Anand Krishnan V. Iyer
Keyword(s):  
Cancer Cells ◽  
Culture Conditions ◽  
Serum Starvation ◽  
Adherent Cells ◽  
Key Factors ◽  
Short Term ◽  
Short Term Exposure ◽  
Highly Sensitive ◽  
Free Media ◽  
Drug Free

The presence of highly resistant cancer cells and the toxicity to normal cells are key factors that limit chemotherapy. Here, we used two models of highly resistant lung cancer cells: (1) adherent cells growing under prolonged periods of serum starvation (PPSS) and (2) cells growing as floating tumorspheres (FTs) to evaluate the effect of Verapamil (VP) in combination with Sorafenib (SF). Compared to cells growing under routine culture conditions (RCCs), PPPS cells or FTs were highly sensitive to short-term exposure (24 h) to VP 100 μM + SF 5 μM (VP100 + SF5). Recovery experiments exposing cells to VP100 + SF5 for 24 h followed by incubation in drug-free media for 48 h demonstrated that while PPSS as well as FT cells were unable to recover, cancer cells and the noncancerous cell line Beas-2B growing under RCCs were less sensitive and were also able to recover significantly. VP100 + SF5 induced significant changes in the expression of protein associated with apoptosis, autophagy, and to a lesser extent necroptosis. Coincubation experiments with z-VAD-FMK, necrostatin 1, or chloroquine showed evidence that necroptosis played a central role. Our data demonstrates that highly resistant cancer cells can be selectively eliminated by VP + SF and that necroptosis plays a central role.

69 REMOVAL OF CUMULUS CELLS AND PRE-INCUBATION IN CYTOCHALASIN B IMPROVE SURVIVAL OF IMMATURE CAT OOCYTES DURING VITRIFICATION

2008 ◽  
Vol 20 (1) ◽  
pp. 115 ◽  
Author(s):  
P. Comizzoli ◽  
D. E. Wildt ◽  
B. S. Pukazhenthi
Keyword(s):  
Room Temperature ◽  
Cytochalasin B ◽  
Cumulus Cells ◽  
Lower Percentage ◽  
Short Term ◽  
No Removal ◽  
Short Term Exposure ◽  
Highly Sensitive ◽  
Rapid Transport ◽  
Oocyte Membrane

Vitrification might be the best option to cryopreserve the immature cat oocyte because our recent studies have demonstrated that COCs are (1) highly sensitive to cryoprotectant (CPA) and require short-term exposure to prevent toxicity, and yet (2) resistant to extreme hyperosmotic conditions when pre-incubated in the cytoskeleton stabilizer cytochalasin B (CB). However, surrounding cumulus cells may inhibit the necessary rapid transport of water and CPA across the oocyte membrane during short-term exposure to vitrification solutions (VS) containing high CPA concentrations. The objective was to examine the influence of cumulus cells on oocyte survival during vitrification with or without pre-incubation in CB. Our metric of focus was the chromatin status after warming and IVM. Grade I immature oocytes (n = 420, 4 replicates) were equally allocated to one of four treatments: T1 (removal of cumulus cells in 0.2% hyaluronidase); T2 (pre-incubation in 7.5 µg mL–1 CB for 20 min); T3 (removal of cumulus cells and pre-incubation in CB (as above)); and T4 (control, no removal of cumulus cells and no pre-incubation in CB). After each treatment, half of the oocytes was washed and immediately cultured for IVM (28 h; denuded oocytes being co-cultured with an equal number of fresh COCs to circumvent the absence of cumulus cells). The other half was exposed to 10% (v/v) ethylene glycol (EG) + 10% (v/v) DMSO for 30 s, followed by exposure to VS (20% EG + 20% DMSO + 0.5 m sucrose) for 20 s at room temperature. Oocytes then were vitrified in <1 µL of VS at the tip of a plastic gutter (2 oocytes/gutter) by direct plunge into liquid nitrogen. After 1 day of storage, vitrified oocytes were warmed in 0.25 m sucrose, extensively washed, and cultured for IVM as described above. All oocytes were then fixed and Hoechst-stained to assess their chromatin status. Oocytes subjected to T1, T2, T3, and T4 without vitrification exhibited no degenerated chromatin (clumped or dispersed) after IVM. After vitrification, the incidence of degenerated chromatin was different (P < 0.05; ANOVA) among treatments, with a lower percentage (P < 0.05) when oocytes were subjected to T3 (15.5 � 3.9%; mean � SD) compared to T1 (26.6 � 3.1%), T2 (48.9 � 3.8%), or T4 (71.1 � 3.8%). The percentage of vitrified oocytes reaching the metaphase II stage (MII) also was different (P < 0.05) among treatments with a higher incidence (P < 0.05) in the T3 group (57.8 � 3.9%) compared to T1 (44.6 � 3.7%), T2 (31.1 � 7.7%), or T4 (15.5 � 3.9%) counterparts. Percentages of non-vitrified oocytes reaching the MII were not different (P > 0.05) among treatments (range, 84.7 to 89.0%) but were higher (P < 0.05) compared to vitrified oocytes. The combination of removal of cumulus cells and pre-incubation in CB prior to vitrification had a cumulative, beneficial influence on cat oocyte survival. Interestingly, removal of cumulus cells imparted a greater benefit on oocyte survival than CB pre-incubation alone.

scholarly journals The Biguanides Metformin and Buformin in Combination with 2-Deoxy-glucose or WZB-117 Inhibit the Viability of Highly Resistant Human Lung Cancer Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Juan Sebastian Yakisich ◽  
Neelam Azad ◽  
Vivek Kaushik ◽  
Anand K. V. Iyer
Keyword(s):  
Lung Cancer ◽  
Synergistic Effect ◽  
Cancer Cells ◽  
Human Lung ◽  
Culture Conditions ◽  
Human Lung Cancer ◽  
Adherent Cells ◽  
Single Drug ◽  
Human Lung Cancer Cells ◽  
H460 Cells

The biguanides metformin (MET) and to a lesser extent buformin (BUF) have recently been shown to exert anticancer effects. In particular, MET targets cancer stem cells (CSCs) in a variety of cancer types but these compounds have not been extensively tested for combination therapy. In this study, we investigated in vitro the anticancer activity of MET and BUF alone or in combination with 2-deoxy-D-glucose (2-DG) and WZB-117 (WZB), which are a glycolysis and a GLUT-1 inhibitor, respectively, in H460 human lung cancer cells growing under three different culture conditions with varying degrees of stemness: (1) routine culture conditions (RCCs), (2) floating lung tumorspheres (LTSs) that are enriched for stem-like cancer cells, and (3) adherent cells under prolonged periods (8-12 days) of serum starvation (PPSS). These cells are highly resistant to conventional anticancer drugs such as paclitaxel, hydroxyurea, and colchicine and display an increased level of stemness markers. As single agents, MET, BUF, 2-DG, and WZB-117 potently inhibited the viability of cells growing under RCCs. Both MET and BUF showed a strong synergistic effect when used in combination with 2-DG. A weak potentiation was observed when used with WZB-117. Under RCCs, H460 cells were more sensitive to MET and BUF and WZB-117 compared to nontumorigenic Beas-2B cells. While LTSs were less sensitive to each single drug, both MET and BUF in combination with 2-DG showed a strong synergistic effect and reduced cell viability to similar levels compared to the parental H460 cells. Adherent cells growing under PPSS were also less sensitive to each single drug, and MET and BUF showed a strong synergistic effect on cell viability in combination with 2-DG. Overall, our data demonstrates that the combination of BGs with either 2-DG or WZB-117 has “broad-spectrum” anticancer activities targeting cells growing under a variety of cell culture conditions with varying degrees of stemness. These properties may be useful to overcome the chemoresistance due to intratumoral heterogeneity found in lung cancer.

Short-Term Exposure of Cancer Cells to Micromolar Doses of Paclitaxel, with or without Hyperthermia, Induces Long-Term Inhibition of Cell Proliferation and Cell Death In Vitro

2007 ◽  
Vol 14 (3) ◽  
pp. 1220-1228 ◽  
Author(s):  
John Michalakis ◽  
Spyros D. Georgatos ◽  
Eelco de Bree ◽  
Hara Polioudaki ◽  
John Romanos ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Cancer Cells ◽  
Short Term ◽  
Short Term Exposure

scholarly journals Menadione : Sodium Orthovanadate Combination Eliminates and Inhibits Migration of Detached Cancer Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Zahid M. Delwar ◽  
Åke Siden ◽  
Mabel H. Cruz ◽  
Juan S. Yakisich
Keyword(s):  
Cancer Cells ◽  
Anticancer Agents ◽  
Clinical Problem ◽  
Sodium Orthovanadate ◽  
Drug Induced ◽  
Free Media ◽  
Drug Free ◽  
Total Elimination ◽  
A549 Lung

Exposure of cancer cells to anticancer agents in cultures induces detachment of cells that are usually considered dead. These drug-induced detached cells (D-IDCs) may represent a clinical problem for chemotherapy since they may survive anoikis, enter the circulation, invade other tissues and resume proliferation, creating a metastasis, especially in tissues where the bioavailability of anticancer agents is not enough to eliminate all cancer cells. In this study we evaluated the antiproliferative effect of menadione : sodium orthovanadate (M : SO) combination on A549 lung cancer cells as well as the ability of M : SO to induce cell detachment. In addition, we followed the fate and chemosensitivity of M : SO-induced detached cells. Using transwell chambers, we found that a fraction of the M : SO-induced detached cells were viable and, furthermore, were able to migrate, re-attach, and resume proliferation when re-incubated in drug-free media. The total elimination of A549 detachment-resistant cells and M : SO-induced detached cells were successfully eliminated by equivalent M : SO concentration (17.5 μM : 17.5 μM). Thus, M : SO prevented cell migration. Similar results were obtained on DBTRG.05MG human glioma cells. Our data guarantee further studies to evaluate the in vivo occurrence of D-IDCs, their implications for invasiveness and metastasis and their sensitivity to anticancer drugs.

scholarly journals B33 Short-Term Exposure to REV-5901 Decreases the Viability of Chemotherapy-Resistant Adherent Lung Cancer Cells and Floating Tumorspheres

2020 ◽  
Vol 15 (2) ◽  
pp. S36-S37
Author(s):  
J.S. Yakisich ◽  
R. Venkatadri ◽  
B. Brinceanu ◽  
C. Woodard ◽  
V. Kaushik ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
Short Term ◽  
Short Term Exposure

scholarly journals Nigericin decreases the viability of multidrug-resistant cancer cells and lung tumorspheres and potentiates the effects of cardiac glycosides

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769431 ◽  
Author(s):  
Juan Sebastian Yakisich ◽  
Neelam Azad ◽  
Vivek Kaushik ◽  
George A O’Doherty ◽  
Anand Krishnan V Iyer
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Multidrug Resistant ◽  
Culture Conditions ◽  
Chemotherapeutic Agents ◽  
Serum Starvation ◽  
Synthetic Analog ◽  
Antitumor Effects ◽  
Anticancer Effects

Multiple factors including tumor heterogeneity and intrinsic or acquired resistance have been associated with drug resistance in lung cancer. Increased stemness and the plasticity of cancer cells have been identified as important mechanisms of resistance; therefore, treatments targeting cancer cells independent of stemness phenotype would be much more effective in treating lung cancer. In this article, we have characterized the anticancer effects of the antibiotic Nigericin in cells displaying varying degrees of stemness and resistance to anticancer drugs, arising from (1) routine culture conditions, (2) prolonged periods of serum starvation. These cells are highly resistant to conventional anticancer drugs such as Paclitaxel, Hydroxyurea, Colchicine, Obatoclax, Wortmannin, and LY294002, and the multidrug-resistant phenotype of cells growing under prolonged periods of serum starvation is likely the result of extensive rewiring of signaling pathways, and (3) lung tumorspheres that are enriched for cancer stem-like cells. We found that Nigericin potently inhibited the viability of cells growing under routine culture conditions, prolonged periods of serum starvation, and lung tumorspheres. In addition, we found that Nigericin downregulated the expression of key proteins in the Wnt canonical signaling pathway such as LRP6, Wnt5a/b, and β-catenin, but promotes β-catenin translocation into the nucleus. The antitumor effects of Nigericin were potentiated by the Wnt activator HLY78 and by therapeutic levels of the US Food and Drug Administration–approved drug Digitoxin and its novel synthetic analog MonoD. We believe that Nigericin may be used in a co-therapy model in combination with other novel chemotherapeutic agents in order to achieve potent inhibition of cancers that display varying degrees of stemness, potentially leading to sustained anticancer effects.

scholarly journals Interactions between Cisplatin and Quercetin at Physiological and Hyperthermic Conditions on Cancer Cells In Vitro and In Vivo

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3271
Author(s):  
Nada Oršolić ◽  
Dyana Odeh ◽  
Maja Jazvinšćak Jembrek ◽  
Jelena Knežević ◽  
Darko Kučan
Keyword(s):  
Bladder Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Combined Treatment ◽  
Short Term ◽  
In Vivo Models ◽  
Short Term Exposure ◽  
Bladder Cancer Cells

Quercetin (QU), a hyperthermic sensitizer, when combined with cisplatin (CP) affects tumor growth. To determine the effects of QU and CP and their interactions, multimodal treatment in vitro and in vivo models under physiological and hyperthermic conditions was performed. In vitro, different sensitivity of T24 and UMUC human bladder cancer cells was observed after short-term exposure to QU (2 h) and CP (1 h). Effects of both compounds were investigated at low and high micromolar concentrations (1 and 50 µM, respectively) under both thermal conditions. QU acted in additive or synergistic manner in combination with CP between physiological condition and hyperthermia. As determined by 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, short-term application of QU and CP reduced cell viability. Clonal assay also indicated that combined treatment with QU and CP is lethal to bladder cancer cells in both conditions. In vivo, CP (5 or 10 mg kg−1) and QU (50 mg kg−1) acted synergistically with hyperthermia (43 °C) and inhibited tumor growth, activated immune effectors and increased mice survival. Our results demonstrate that combined treatment with CP and QU may increase death of tumor cells in physiological and hyperthermic conditions which could be clinically relevant in locoregional chemotherapy.

The Effect of Dimethyl Sulfoxide on In Vitro Platelet Function

1976 ◽  
Vol 36 (01) ◽  
pp. 221-229 ◽  
Author(s):  
Charles A. Schiffer ◽  
Caroline L. Whitaker ◽  
Morton Schmukler ◽  
Joseph Aisner ◽  
Steven L. Hilbert
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Dimethyl Sulfoxide ◽  
Platelet Function ◽  
Platelet Volume ◽  
Short Term ◽  
Platelet Factor ◽  
Short Term Exposure ◽  
Structural Abnormalities

SummaryAlthough dimethyl sulfoxide (DMSO) has been used extensively as a cryopreservative for platelets there are few studies dealing with the effect of DMSO on platelet function. Using techniques similar to those employed in platelet cryopreservation platelets were incubated with final concentrations of 2-10% DMSO at 25° C. After exposure to 5 and 10% DMSO platelets remained discoid and electron micrographs revealed no structural abnormalities. There was no significant change in platelet count. In terms of injury to platelet membranes, there was no increased availability of platelet factor-3 or leakage of nucleotides, 5 hydroxytryptamine (5HT) or glycosidases with final DMSO concentrations of 2.5, 5 and 10% DMSO. Thrombin stimulated nucleotide and 5HT release was reduced by 10% DMSO. Impairment of thrombin induced glycosidase release was noted at lower DMSO concentrations and was dose related. Similarly, aggregation to ADP was progressively impaired at DMSO concentrations from 1-5% and was dose related. After the platelets exposed to DMSO were washed, however, aggregation and release returned to control values. Platelet aggregation by epinephrine was also inhibited by DMSO and this could not be corrected by washing the platelets. DMSO-plasma solutions are hypertonic but only minimal increases in platelet volume (at 10% DMSO) could be detected. Shrinkage of platelets was seen with hypertonic solutions of sodium chloride or sucrose suggesting that the rapid transmembrane passage of DMSO prevented significant shifts of water. These studies demonstrate that there are minimal irreversible alterations in in vitro platelet function after short-term exposure to DMSO.

Efficacy of the detection of the early symptoms of Cancer cell, Prevention and the diagnosis procedure

2020 ◽  
Vol 16 ◽  
Author(s):  
Md Mahfujul Islam ◽  
Md Al Amin Molla
Keyword(s):  
Cancer Cells ◽  
Reference Lists ◽  
Web Of Science ◽  
Screening Program ◽  
Bibliographic Databases ◽  
Controlled Trials ◽  
Conference Paper ◽  
Cancer Awareness ◽  
Short Term ◽  
Randomized Controlled

: The aim to examine the signs for the potency of interventions to raise cancer awareness along with promote early demonstration in most cancers to share with future and policy investigation. Several peer-reviewed journals as well as books, conference paper and authentic website (like as NCBI, PubMed, CRI, CRU, Google Scholar, MEDLINE, Web of Science, etc.) Also, we looked for bibliographic databases and reference lists Such as randomized controlled trials of interventions brought to Individuals and commanded or uncontrolled reports of interventions brought to communities. The results found the signs that interventions reach to people subconsciously increase the cancer awareness from the short term and inadequate signs they advertise premature demonstration. This analysis helps to find appropriate info about categorizing the early indicators of many kinds of cancer cells on addition to appropriate guidelines to conquer cancer in low-Mid center income areas. Whereas contained the structured screening program, which helps detect cancer early and having a heightened chance of therapeutic and treatment content, taking essential measures to elevate the consciousness of the detectable symptoms.

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