scholarly journals Growth Effects of Some Platinum(II) Complexes with Sulfur-Containing Carrier Ligands on MCF7 Human Breast Cancer Cell Line upon Simultaneous Administration with Taxol

2002 ◽  
Vol 9 (1-2) ◽  
pp. 33-43 ◽  
Author(s):  
Gordana Bogdanović ◽  
Vesna Kojić ◽  
Tatjana Srdić ◽  
Dimitar Jakimov ◽  
Miloš I. Djuran ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Recovery Period ◽  
Cancer Cell Line ◽  
Inhibitory Effect ◽  
Mcf7 Cells ◽  
Cisplatin Analogues ◽  
Ic50 Values ◽  
G2m Phase ◽  
Induced Apoptosis

The platinum (II)complexes, cis-[PtCl2(CH3SCH2CH2SCH3)] (Pt1), cis-[PtCl2(dmso)2] (dmso is dimethylsulfoxide; Pt2) and cis-[PtCl2(NH3)2] (cisplatin), and taxol (T) have been tested at different equimolar concentrations. Cells were exposed to complexes for 2 h and left to recover in fresh medium for 24, 48 or 72 h. Growth inhibition was measured by tetrazolium WST1 assay Analyses of the cell cycle, and apoptosis were performed by flow cytometry, at the same exposure times. The IC50 value of each platinum(II) complex as well as combination index (CI; platinum(II) complex + taxol) for various cytotoxicity levels were determined by median effects analysis.MCF7 cells were found to be sensitive to both Pt1 and Pt2 complexe These cisplatin analogues influenced the cell growth more effectively as compared to cisplatin. Cytotoxic effect was concentration and time-dependent. Profound growth inhibitory effect was observed for Pt1 complex, across all its concentrations at all recovery periods. A plateau effect was achieved three days after treatment at Pt1 concentrations ≤ 1 μM. Pt2, however, decreased MCF7 cells survival only for the first 24 h ranging between 50-55%. Pt2 cytotoxicity sharply decreased thereafter, approaching 2 h - treatment cytotoxicity level. The median IC50 values for Pt1 and Pt2 were similar (0.337 and 0.3051 μM, respectively) but only for the first 24 h. The IC50 values for Pt1 strongly depend on the recovery period. On simultaneos exposure of cells to taxol and platinum(II) complexes no consistent effect was found. The Cls for combinations of taxol with Pt1 or Pt2 revealed cytotoxic effects that were in most Cases synergistic (Pt1) or less than addtiive (Pt2). Flow cytometry analysis has shown that each platinum(II) complex induced apoptosis in MCF7 cells. The level of apoptosis correlated with cytotoxicity level for the range concentrations. Both cisplatin analogues, at IC50 concentrations, increased the number of MCF7 cells in G0G1 phase of cell cycle. Pt2-treated cells remained arrested in G0G1 phase up to 72 h after treatment. Combination of Pt2 and taxol caused further arrest of cells in G0G1 phase (24 h) in parallel with strong decrement of G2M phase cells.

Antitumor Activity and Underlying Mechanism of Phomoxanthone B in MCF7 Cells

2020 ◽  
Vol 20 ◽  
Author(s):  
Chuan Chen ◽  
Ziyue Zhao ◽  
Qian Dong ◽  
XueHui Gao ◽  
Huibin Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Antitumor Activity ◽  
Oxidative Phosphorylation ◽  
Tumor Cells ◽  
Transcriptome Analysis ◽  
Mcf7 Cells ◽  
Er Positive ◽  
Induced Apoptosis ◽  
Positive Breast Cancer

Background:: Xanthones are a class of heterocyclic natural products, which are promising sources of anticancer leads. Phomoxanthone B（PXB）and Phomoxanthone A（PXA）are xanthone dimers. PXA is well studied as an anti-cancer agent, but PXB is not. In our study, PXB was isolated from the endophytic fungus Phomopsis sp. By254. Objective:: The purpose of this study was to identify the underlying anti-tumor mechanisms of PXB in breast cancer MCF7 cell line. Methods:: Apoptosis, cell cycle, proliferation, invasion and migration assays were used to assess the antitumor activity of PXB. RNA sequencing was used to analyze the effect of PXB treatment on gene expression in MCF7 cells. Results:: PXB showed cytotoxicity toward a variety of tumor cells, especially MCF7 cells. PXB inhibited the migration and invasion, arrested cell cycle at G2/M phase and induced apoptosis associated with caspase-3 activation in MCF7 cells. The detailed transcriptome analysis revealed that PXB affected several pathways related to tumorigenesis, metabolisms-, and oxidative phosphorylation in MCF7 cells. KEGG transcriptome analysis revealed that PXB upregulated pro-survival signal pathways such as MAPK, PI3K-AKT and STAT3 pathways. We found that PXB also significantly upregulated the expression of IL24, DDIT3 and XAF1, which may contribute to PXB-induced apoptosis. We further found that PXB may downregulate oxidative phosphorylation by decreasing the expression of electron transport chain genes, especially MT-ND1, which is a potential unfavorable prognostic marker for ER-positive breast cancer. Conclusion:: PXB exerts strong cytotoxicity against human tumor cells and has a potential for ER-positive breast cancer treatment.

Evaluating the Effect of Cinnarizine on Promastigotes and Amastigotes forms of Leishmania major

2020 ◽  
Vol 20 (4) ◽  
pp. 550-555 ◽  
Author(s):  
Lima Asgharpour Sarouey ◽  
Parvaneh Rahimi-Moghaddam ◽  
Fatemeh Tabatabaie ◽  
Khadijeh Khanaliha
Keyword(s):  
Flow Cytometry ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Inhibitory Effect ◽  
Control Group ◽  
Secondary Infections ◽  
Ic50 Values ◽  
J774 Cells ◽  
Mtt Assays

: As an important global disease, cutaneous leishmaniasis is associated with complications such as secondary infections and atrophic scars. The first line treatment with antimonials is expensive and reported to have serious side effects and enhance resistance development. The main objective of this study was to evaluate the effect of Cinnarizine on standard strains of Leishmania major because of paucity of information on this subject. Methods: In this experimental study, four concentrations of the drug (5, 10, 15 and 20 μg/ml) were added to Leishmania major cultures at 24, 48 and 72 hours intervals. MTT assays were performed to determine parasite viability and drug toxicity. Leishmania major promastigotes were augmented to the in vitro cultured macrophages (J774 cells) and then incubated for 72 hours. Half maximal inhibitory concentration (IC50) was ascertained by counting parasites. The inhibitory effect of the drug was compared with that of Glucantime. Flow-cytometry was performed to investigate apoptosis. Each test was repeated thrice. Results: The IC50 values of Cinnarizine after 72 hours were calculated to be 34.76 μg/ml and 23.73 μg/ml for promastigotes and amastigotes, respectively. The results of MTT assays showed 48 % promastigote viability after 72 hour-exposure to Cinnarizine at 20 μg/ml concentration. Programmed cell death in promastigote- and amastigote-infected macrophages was quantified to be 13.66 % and 98.7 %, respectively. Flow- cytometry analysis indicated that Cinnarizine induced early and late apoptosis in parasites. All treatments produced results which differed significantly from control group (P<0.05). Conclusion: Cinnarizine showed low toxicity with anti-leishmanial and apoptosis effects on both promastigote and intracellular amastigote forms. Therefore, we may suggest further assessment on animal models of this drug as candidates for cutaneous leishmaniasis therapy.

Relationship between the As2O3 Induced Expression of NF-κB and Drug Resistance in K562/ADR Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4414-4414
Author(s):  
Xiao-hong Zhang ◽  
Li-da Su ◽  
Xiao-ying Zhao ◽  
Qing-hua Lv
Keyword(s):  
Flow Cytometry ◽  
Drug Resistance ◽  
K562 Cells ◽  
Suppressive Effect ◽  
Resistance Mechanisms ◽  
Leukemic Cells ◽  
Ic50 Values ◽  
Induced Apoptosis ◽  
The Relationship ◽  
Cells Cultured

Abstract Summery: Anti-apoptosis is one of drug resistance mechanisms in leukemic cells. It was found in our early study that As2O3 can induce apoptosis of K562 cells, and this effect involve the degradation of IκB-αand consequently the activation of NF-κB. The relationship between drug resistance of leukemic cells and the expression of both IκB-αand NF-κB associated with apoptosis induced by arsenic trioxide(As2O3) was studied in K562 and K562/ADR cells. Methods: Apoptosis was induced in K562 and K562/ADR cells cultured with As2O3 in different concentrations. Western blot was used to analyze the expression of NF-κB in nuclear and IκB-α in cytoplasm of these cells. Apoptosis and degradation of IκB-αprotein were also observed by flow cytometry. Results: The suppressive effect of As2O3 on proliferation of K562/ADR was lower than that in K562 cell, IC50 values were 19.07μmol/L and 5.26μmol/L, respectively. After exposure to As2O3, the ratio of apoptosis cells increased with the concentration of As2O3 in K562 cells, from(13.25±1.83)% to (50.56±8.62)% with variation of As2O3 from 1μmol/L to 4μmol/L(P<0.05). The ratio of apoptosis cells in K562/ADR cultured with 4μmol/L As2O3 was significantly lower than that in K562 cells, (8.00±1.47)% vs. (50.56±8.62)%, (P<0.05). The level of IκB-α in K562 cytoplasm was down-regulated from (88.07±0.99)% to (49.21±0.95)%, (P<0.01) after As2O3 stimulation, while NF-κB in nuclear was up-regulated, that was not found in K562/ADR cells. Conclusion: As2O3 could induce apoptosis of K562 cells, associated with the degradation of IκB-αand the activation of NF-κB. There were resistance to As2O3 induced apoptosis and an abnormal regulation of NF-κB expression by As2O3 in K562/ADR cells.

Apoptosis Was Induced by Casticin in Acute Myelocytic Leukemia Cells

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3991-3991
Author(s):  
Jie Jin ◽  
Jia-Kun Shen ◽  
Hua-ping Du ◽  
Min Yang ◽  
Yun-Gui Wang
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Cell Death ◽  
Leukemic Cell ◽  
K562 Cells ◽  
Acute Myelocytic Leukemia ◽  
Myelocytic Leukemia ◽  
Cycle Arrest ◽  
M Phase ◽  
Ic50 Values

Abstract Casticin, a component from Vitex rotundifolia wich was widely used as an anti-inflammatory agent in Chinese traditional medicine, was reported to have anti-tumor activities in lung cancer and breast cancer. There are yet no reports on roles against acute myelocytic leukemia (AML). This study aims to elucidate the anti-leukemic activity of casticin on AML cells. We investigated the efficient efficacy and the mechanisms by which casticin triggers cell death in AML cells by analyzing cell cycle perturbations, apoptosis-related marker expression. Cell viability was measured by MTT method; apoptosis and cell cycle arrest were determined by flow cytometry and AV-PI assay. Western blot was performed to measure the apoptosis-related marker. Concentration-dependant cell deaths were observed in AML cell lines including K562, U937 and THP-1, with IC50 values of 24h (hours) being 47.4μM, 67.8μM and 61.7μM, respectively. Time-dependant cell deaths were also observed. At the concentration of 20μM casticin, 45.7%, 76.1% and 80.9% of K562 cells were inhibited at 24h, 48h and 72h, respectively; 24.7%, 30% and 61% of U937 cells were inhibited at 24h, 48h and 72h, respectively; while for THP-1, 29%, 41.8% and 53.9% were inhibited at 24h, 48h and 72h, respectively. Apoptosis was found using AV-PI staining by flow cytometry analysis. We observed an obvious G2/M phase increase prolongation in casticin treated K562 cells. BThe distribitions of G2/M phase were 2.9%, 33.6%, 75.3%, 54.9%, 29.7% and 27.0% in K562 cells after treated by 20μM casticin for 0h, 6h, 12h, 24h, 36h and 48h, respectively. Furthermore, apoptosis-related proteins, PARP and caspase 3, were cleaved in casticin treated K562 cells. Taken together, these results demonstrated that casticin can induce leukemic cell death through apoptosis, suggesting that casticin could be a promising therapeutic agent against acute myeloid leukemia.

scholarly journals Evaluation of Anticancer Activity of Olmesartan and Ramipril On A549 Cell Line

2018 ◽  
Vol 11 (3) ◽  
pp. 1351-1357 ◽  
Author(s):  
E Gayathri ◽  
K. Punnagai ◽  
D. Darling Chellathai
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Anticancer Activity ◽  
Cell Line ◽  
A549 Cell ◽  
Enzyme Inhibitor ◽  
A549 Cell Line ◽  
Ic50 Values

Angiotensin Converting Enzyme Inhibitor (ACEI) and Angiotensin II type 1 receptor antagonist (ARBs) are the most efficient cardiovascular drugs and exhibited efficient cytostatic activity in vitro in many malignant and normal cells1.OBJECTIVE: This study aims to assess the anticancer activity of these two drugs in a dose dependant manner using A549 cell line through MTT assay and Cell cycle analysis.. MATERIALS AND METHODS: Ramipril and Olmesartan were added to A549 at various concentrations ranging from 10⁻⁶ to 10mM.The dot plot of the cytotoxicity results were used to extrapolate the IC50 values. The dot plot of flow cytometry results were used to extrapolate the DNA percentage in phases of cell cycle. The plates were read at 570 nm by using a PERCLIN ELMER (multimode reader). Measurements for concentration required for 50% inhibition was noted. RESULTS: Ramipril and Olmesartan were added to A549 at various concentrations ranging from 10⁻⁶ to 10mM.The dot plot of the cytotoxicity results were used to extrapolate the IC50 values. The dot plot of flow cytometry results were used to extrapolate the DNA percentage in phases of cell cycle.

scholarly journals TR57, an Inhibitor of the Integrated Stress Response, Is Synergistic with Venetoclax Against CLL Cells, Independent of Their TP53 Status

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1735-1735
Author(s):  
Narjis Fatima ◽  
Yandong Shen ◽  
Kyle R Crassini ◽  
Edwin Iwanowicz ◽  
Richard Christopherson ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Stress Response ◽  
Stromal Cell ◽  
Single Agent ◽  
Significant Proportion ◽  
Integrated Stress Response ◽  
Significant Difference ◽  
Highly Effective ◽  
Ic50 Values

Introduction Despite recent advances in the treatment of chronic lymphocytic leukemia (CLL), a significant proportion of patients still relapse with drug-resistant disease. Patients with deletions and/or mutations in TP53 remain a poor prognostic sub-group. There remains a need for on-going research on identifying novel treatment strategies. We have investigated the therapeutic potential of TR57 (Madera Therapeutics, USA), as a single agent and in combination with the Bcl-2 inhibitor venetoclax in CLL. TR57 is an inhibitor of the integrated stress response (ISR) and has shown efficacy in pre-clinical studies of breast cancer. Methods TR57 and venetoclax, as single agents or in combination, were studied against primary CLL cells co-cultured with CD40L-expressing fibroblasts to mimic the tumour microenvironment (TME). The effects of the drugs were also assessed against an OSU-CLL TP53 knock-out cell line generated using CRISPr Cas-9. Cell viability was assessed using the mitochondrial membrane potential dye DiIC1(5), propidium iodide (PI) and flow cytometry. Cytotoxic synergy between TR57 and venetoclax was determined by calculating combination indices (CI) using the CompuSyn software, with CI values of <1 indicative of synergy. Primary CLL cells were stimulated into cycle primary using Dsp30 in combination with IL-2. Cell cycle distribution and proliferation were analysed by flow cytometry using PI and CFSE, respectively. The migratory and adhesive capacities of primary CLL cells was assessed using stroma-derived factor 1a and by assessing expression of CXCR4 and CD49d. The mechanisms of the synergy between TR57 and venetoclax were studied by immunoblotting. Statistical analyses were performed using the students t-test with P-values of < 0.05 considered significant. Results TR57 was cytotoxic towards primary CLL cells in a nanomolar range, with IC50 values of 38 ± 1.38 nM and 287 ± 50.45 nM against cells in medium and stromal cell co-culture, respectively. No significant difference was observed in the sensitivity of samples with ATM or TP53 aberrations (n=12). Synergy between TR57 and venetoclax against CLL cells in stromal cell co-culture was consistent with a significant (P < 0.001) decrease in the IC50 for both drugs (Figure 1A). A CI value of 0.13 was calculated at a fractional effect of 0.5. TR57 was cytotoxic towards OSU-CLL and OSU-CLLTP53ko cells, with IC50 values of 3.98 ± 1.03 nM and 90.7 ± 3.51 nM, respectively. Synergy between TR57 and venetoclax was evident in both lines with a CI = 0.1 at Fa 0.5. Dose-response analyses in the OSU-CLLTP53ko line are shown in Figure 1B. Following stimulation of primary CLL cells with Dsp30/IL-2 we observed a significant (P < 0.01) increase in the proportion of cells in S, G2 and M phases, which was consistent with an increase in cell proliferation. TR57 and venetoclax in combination had a greater effect than individual drug treatments, significantly reduced the proportion of cells in these cell cycle phases and the proliferative fraction of cells. TR57 and venetoclax in combination also had a significantly greater effect on the migratory capacity (P < 0.05) of CLL cells and on the expression of CXCR4 and CD49d (P < 0.001) than either drug as a single agent. Immunoblotting of primary CLL and OSU-CLL cells showed that treatment with TR57 decreased expression of Grp78, which supports the notion that this drug may function through inhibition of the ISR. We also observed that TR57, alone and in combination with venetoclax, down-regulated the expression of the pro-survival Mcl-1 and Bcl-2 proteins, up-regulated expression of the pro-apoptotic Noxa and Bax proteins and inhibited the phosphorylation of AKT and ERK1/2-MAPK. Conclusions The data presented demonstrate that TR57 is cytotoxic towards CLL cells under in vitro conditions that mimic the TME and cells with lesions of the TP53 pathway. The synergy observed between TR57 and venetoclax suggests that the drug combination may be highly effective at limiting the survival and proliferation of CLL cells as well as their ability to migrate to, and be retained within, the TME. The mechanisms of this synergy include a shift towards a pro-apoptotic balance in Bcl-2 family proteins and inhibition of signalling via the AKT and ERK1/2-MAPK pathways. Collectively, these data suggest that TR57 alone and in combination with venetoclax may be a highly effective treatment strategy for high risk CLL. Disclosures Iwanowicz: Madera Therapeutics, LLC: Other: President;Ownership.

scholarly journals ONC-212 (I-39), a Novel Inhibitor of the UPR, Is Cytotoxic and Cytostatic Against CLL Cells Under in Vitro Conditions That Mimic the Tumor Microenvironment

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3145-3145
Author(s):  
Narjis Rizwan ◽  
Yandong Shen ◽  
Edwin Iwanowicz ◽  
Stephen P. Mulligan ◽  
Kyle R Crassini ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Effective Treatment ◽  
Cell Line ◽  
Propidium Iodide ◽  
Cycle Arrest ◽  
Migratory Capacity ◽  
Ic50 Values ◽  
Cells Cultured

Abstract Introduction Despite the revolution in the treatment of chronic lymphocytic leukemia (CLL) over the past decade with the introduction of novel inhibitors targeting the B-cell receptor (BCR) signaling pathway and the Bcl-2 family of proteins, relapse is still common. Recent studies suggest that imipridones, a novel class of small molecule agents that attenuate mitochondrial respiration and modulate an immune response against cancer cells, may be an effective treatment option for several difficult to treat cancers. We investigated the effects of the imipridone, ONC-212 (I-39, first published by Nanjing Gator Meditech), as a potential therapeutic strategy for CLL using the OSU-CLL cell line and a modified OSU-CLL line in which TP53 was stably knocked out and primary CLL cells cultured under conditions that mimic the tumour microenvironment (TME). Methodology Primary CLL cells were co-cultured with CD40L-expressing fibroblasts to mimic aspects of the TME. The cytotoxicity of ONC-212 was assessed using the mitochondrial dye DiIC1(5), propidium iodide and flow cytometry. The effects of the drug on the adhesive and migratory capacity of primary CLL cells were evaluated using antibodies against CD49d, CXCR4 and an in vitro migration assay using stroma-derived factor 1a (SDF1-α). Changes in protein expression were assessed by immuno-blotting. The effects of ONC-212 on the cell cycle and proliferation were assessed using the OSU-CLL cell line. OSU-CLL cells were modified using the CRISPr-Cas9 technology to be TP53 deficient (OSU-TP53ko). The proportion of cells in each cycle phase was determined using propidium iodide and flow cytometry. Cell proliferation rates were determined using carboxyfluorescein succinimidyl ester (CFSE) and flow cytometry. Results ONC-212 induced apoptosis in a dose-dependent manner in primary CLL cells cultured in medium alone or in contact with CD40L-fibroblasts (Figure 1); the IC50 values were 72.97 nm +/- 1.45 nM and 472 +/- 2.04 nM, respectively. OSU-CLL and OSU-TP53ko cells were also sensitive to ONC-212, although the TP53 deficient line was less sensitive than OSU-CLL(Figure 1). IC50 values for the cell lines were 22 +/- 1.37 nM (OSU-CLL) and 48 +/- 3.25 nM (OSU-TP53ko). ONC-212 induced cell cycle arrest of the OSU-CLL and OSU-TP53ko lines at the G1/S phase transition. This effect was concomitant with a significant reduction in the proliferation of both lines. ONC-212 significantly down-regulated expression of the adhesion molecule CD49d and the G-coupled protein receptor CXCR4 on primary CLL cells. Down-regulation of CXCR4 translated into a decrease in the migratory capacity of CLL cells along an SDF1-α gradient. Immunoblotting suggested the mechanisms of action of ONC-212 include inhibition of ERK1/2-MAPK, a decrease in the Bcl-2/Bax ratio and upregulation of the pro-apoptotic Puma and Bak proteins. Conclusions ONC-212 is highly effective against CLL cells at nanomolar concentrations, against cells cultured under conditions that mimic aspects of the TME and against TP53-deficient cells. ONC-212 has cytotoxic effects, induces cell cycle arrest, slows proliferation and inhibits the mechanisms by which CLL cells migrate to and are retained within the TME. ONC-212 inhibited signaling downstream of the BCR and induced a pro-apoptotic 'tipping' of the balance in expression of BCl-2 family proteins. These data suggest ONC-212 may represent an effective treatment for CLL, particularly for patients who have high risk, relapsed/refractory disease associated with loss or mutation of TP53. Disclosures No relevant conflicts of interest to declare.

scholarly journals Isoliquiritigenin inhibits the proliferation, migration and metastasis of Hep3B cells via suppressing cyclin D1 and PI3K/AKT pathway

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Yun Huang ◽  
Chen Liu ◽  
Wu-Cha Zeng ◽  
Guo-Yan Xu ◽  
Jian-Min Wu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Inhibitory Effect ◽  
Cycle Arrest ◽  
Novel Drugs ◽  
Epithelial Marker ◽  
Hep3b Cells ◽  
Induced Apoptosis

Abstract The overall survival rate of patients with hepatocellular carcinoma (HCC) has remained unchanged over the last several decades. Therefore, novel drugs and therapies are required for HCC treatment. Isoliquiritigenin (ISL), a natural flavonoid predominantly isolated from the traditional Chinese medicine Glycyrrhizae Radix (Licorice), has a high anticancer potential and broad application value in various cancers. Here, we aimed to investigate the anticancer role of ISL in the HCC cell line Hep3B. Functional analysis revealed that ISL inhibited the proliferation of Hep3B cells by causing G1/S cell cycle arrest in vitro. Meanwhile, the inhibitory effect of ISL on proliferation was also observed in vivo. Further analysis revealed that ISL could suppress the migration and metastasis of Hep3B cells in vitro and in vivo. Mechanistic analysis revealed that ISL inhibited cyclin D1 and up-regulated the proteins P21, P27 that negatively regulate the cell cycle. Furthermore, ISL induced apoptosis while inhibiting cell cycle transition. In addition, phosphatidylinositol 3′-kinase/protein kinase B (PI3K/AKT) signal pathway was suppressed by ISL treatment, and the epithelial marker E-cadherin was up-regulated when the mesenchymal markers Vimentin and N-cadherin were down-regulated. In brief, our findings suggest that ISL could be a promising agent for preventing HCC tumorigenesis and metastasis.

In vitro Cytotoxicity, Apoptosis, Effects on Cell Cycle Kinetics and Schedule-Dependent Effects Induced by Paclitaxel on C6 and CHO-K1 Cell Lines

2020 ◽  
Author(s):  
Mohammad Aamir Bhat ◽  
Chandresh Varshneya ◽  
Pallavi Bhardwaj ◽  
Rajendra Damu Patel ◽  
Ashok Kumar Panda
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Prolonged Exposure ◽  
Fluorescent Microscopy ◽  
In Vitro Cytotoxicity ◽  
M Phase ◽  
Ic50 Values ◽  
Induced Apoptosis ◽  
In Vitro Data

Exposure of C6 and CHO-K1 cells to different concentrations of the antineoplastic drug paclitaxel resulted in a loss of cellular viability. The percentage of surviving cells fell significantly after 48 hours of treatment and IC50 values observed were between 0.5 to 0.75 and 0.25 to 0.75 µg/ml in C6 and CHO-K1 cells, respectively. No significant cytotoxicity was observed after 24 hours of treatment and cells incubated at higher concentrations of paclitaxel showed increased survivability. Paclitaxel induced apoptosis by caspase 3/7 activation and caused accumulation of cells in the G2/M phase of the cell cycle. Upon fluorescent microscopy, both the cell lines lost the morphology, confluence and adherence at 24 hours but effects were much more pronounced at 48 hours of treatment. The in vitro data suggested that paclitaxel is highly effective when there is prolonged exposure of tumor to the drug rather than increasing the intratumoral or biophasic concentration of the drug. 

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