The Effect of Lycopene Preexposure on UV-B-Irradiated Human Keratinocytes

Lycopene has been reported as the antioxidant most quickly depleted in skin upon UV irradiation, and thus it might play a protective role. Our goal was to investigate the effects of preexposure to lycopene on UV-B-irradiated skin cells. Cells were exposed for 24 h to 10 M lycopene, and subsequently irradiated and left to recover for another 24 h period. Thereafter, several parameters were analyzed by FCM and RT-PCR: genotoxicity/clastogenicity by assessing the cell cycle distribution; apoptosis by performing the Annexin-V assay and analyzing gene expression of apoptosis biomarkers; and oxidative stress by ROS quantification. Lycopene did not significantly affect the profile of apoptotic, necrotic and viable cells in nonirradiated cells neither showed cytostatic effects. However, irradiated cells previously treated with lycopene showed an increase in both dead and viable subpopulations compared to nonexposed irradiated cells. In irradiated cells, lycopene preexposure resulted in overexpression ofBAXgene compared to nonexposed irradiated cells. This was accompanied by a cell cycle delay at S-phase transition and consequent decrease of cells in G0/G1 phase. Thus, lycopene seems to play a corrective role in irradiated cells depending on the level of photodamage. Thus, our findings may have implications for the management of skin cancer.

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Sensitization of breast cancer cells to doxorubicin via stable cell line generation and overexpression of DFF40

Biochemistry and Cell Biology ◽

10.1139/bcb-2015-0007 ◽

2015 ◽

Vol 93 (6) ◽

pp. 604-610 ◽

Cited By ~ 6

Author(s):

Fatemeh Bagheri ◽

Shahrokh Safarian ◽

Mohamadreza Baghaban Eslaminejad ◽

Nader Sheibani

Keyword(s):

Cell Cycle ◽

Annexin V ◽

Eukaryotic Expression ◽

Stable Cell Line ◽

Cell Cycle Distribution ◽

Distribution Analysis ◽

Transfected Cells ◽

Dna Laddering ◽

Stable Cell Line Generation ◽

Cell Line Generation

There are a number of reports demonstrating a relationship between the alterations in DFF40 expression and development of some cancers. Here, increased DFF40 expression in T-47D cells in the presence of doxorubicin was envisaged for therapeutic usage. The T-47D cells were transfected with an eukaryotic expression vector encoding the DFF40 cDNA. Following incubation with doxorubicin, propidium iodide (PI) staining was used for cell cycle distribution analysis. The rates of apoptosis were determined by annexin V/PI staining. Apoptosis was also evaluated using the DNA laddering analysis. The viability of DFF40-transfected cells incubated with doxorubicin was significantly decreased compared with control cells. However, there were no substantial changes in the cell cycle distribution of pIRES2-DFF40 cells incubated with doxorubicin compared to control cells. The expression of DFF40, without doxorubicin incubation, had also no significant effect on the cell cycle distribution. There was no DNA laddering in cells transfected with the empty pIRES2 vector when incubated with doxorubicin. In contrast, DNA laddering was observed in DFF40 transfected cells in the presence of doxorubicin after 48 h. Also, the expression of DFF40 and DFF45 was increased in DFF40 transfected cells in the presence of doxorubicin enhancing cell death. Collectively our results indicated that co-treatment of DFF40-transfected cells with doxorubicin can enhance the killing of these tumor cells via apoptosis. Thus, modulation of DFF40 level may be a beneficial strategy for treatment of chemo-resistant cancers.

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Biological Evaluation of Arylsemicarbazone Derivatives as Potential Anticancer Agents

Pharmaceuticals ◽

10.3390/ph12040169 ◽

2019 ◽

Vol 12 (4) ◽

pp. 169

Author(s):

Anne Cecília Nascimento da Cruz ◽

Dalci José Brondani ◽

Temístocles I´talo de Santana ◽

Lucas Oliveira da Silva ◽

Elizabeth Fernanda da Oliveira Borba ◽

...

Keyword(s):

Cell Cycle ◽

Cell Lines ◽

Anticancer Agents ◽

Cell Cycle Progression ◽

Annexin V ◽

Biological Evaluation ◽

G1 Phase ◽

Cellular Functions ◽

Ic50 Values ◽

Annexin V Assay

Fourteen arylsemicarbazone derivatives were synthesized and evaluated in order to find agents with potential anticancer activity. Cytotoxic screening was performed against K562, HL-60, MOLT-4, HEp-2, NCI-H292, HT-29 and MCF-7 tumor cell lines. Compounds 3c and 4a were active against the tested cancer cell lines, being more cytotoxic for the HL-60 cell line with IC50 values of 13.08 μM and 11.38 μM, respectively. Regarding the protein kinase inhibition assay, 3c inhibited seven different kinases and 4a strongly inhibited the CK1δ/ε kinase. The studied kinases are involved in several cellular functions such as proliferation, migration, cell death and cell cycle progression. Additional analysis by flow cytometry revealed that 3c and 4a caused depolarization of the mitochondrial membrane, suggesting apoptosis mediated by the intrinsic pathway. Compound 3c induced arrest in G1 phase of the cell cycle on HL-60 cells, and in the annexin V assay approximately 50% of cells were in apoptosis at the highest concentration tested (26 μM). Compound 4a inhibited cell cycle by accumulation of abnormal postmitotic cells at G1 phase and induced DNA fragmentation at the highest concentration (22 μM).

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Carvacrol Induced Program Cell Death and Cell Cycle Arrest in Androgen-Independent Human Prostate Cancer Cells via Inhibition of Notch Signaling

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190731152942 ◽

2019 ◽

Vol 19 (13) ◽

pp. 1588-1608 ◽

Cited By ~ 3

Author(s):

Fahad Khan ◽

Vipendra K. Singh ◽

Mohd Saeed ◽

Mohd A. Kausar ◽

Irfan A. Ansari

Keyword(s):

Prostate Cancer ◽

Cell Cycle ◽

Notch Signaling ◽

Cancer Cells ◽

Prostate Cancer Cell ◽

Cancer Cell Line ◽

Annexin V ◽

Prostate Cancer Cell Line ◽

Prostate Cancer Cells ◽

Annexin V Assay

Background: Several studies have revealed that abnormal activation of Notch signaling is closely related with the development and progression of prostate cancer. Although there are numerous therapeutic strategies, a more effective modality with least side effects is urgently required for the treatment of prostate cancer. Carvacrol is a monoterpenoid phenol and majorly present in the essential oils of Lamiaceae family plants. Many previous reports have shown various biological activities of carvacrol like antioxidant, antiinflammatory and anticancer properties. Recently, we have shown potent anticancer property of carvacrol against prostate cancer cell line DU145. In the current study, we report the chemopreventive and therapeutic potential of carvacrol against another prostate cancer cell line PC-3 with its detailed mechanism of action. Methods: To determine the effect of the carvacrol on prostate cancer cells, the cell viability was estimated by MTT assay and cell death was estimated by LDH release assay. The apoptotic assay was performed by DAPI staining and FITC-Annexin V assay. Reactive Oxygen Species (ROS) was estimated by DCFDA method. Cell cycle analysis was performed by flow cytometry. Gene expression analysis was performed by quantitative real time PCR. Results: Our results suggested that the carvacrol treatment significantly reduced the cell viability of PC-3 cells in a dose- and time-dependent manner. The antiproliferative action of carvacrol was correlated with apoptosis which was confirmed by nuclear condensation, FITC-Annexin V assay, modulation in expression of Bax, Bcl-2 and caspase activation. The mechanistic insight into carvacrol-induced apoptosis leads to finding of elevated level of Reactive Oxygen Species (ROS) and mitochondrial membrane potential disruption. Cell cycle analysis revealed that carvacrol prevented cell cycle in G0/G1 that was associated with decline in expression of cyclin D1 and Cyclin-Dependent Kinase 4 (CDK4) and augmented expression of CDK inhibitor p21. Having been said the role of hyperactivation of Notch signaling in prostate cancer, we also deciphered that carvacrol could inhibit Notch signaling in PC-3 cells via downregulation of Notch-1, and Jagged-1. Conclusion: Thus, our previous and current findings have established the strong potential of carvacrol as a chemopreventive agent against androgen-independent human prostate cancer cells.

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Hsa-miR-186-5p regulates TGFβ signaling pathway through expression suppression of SMAD6 and SMAD7 genes in colorectal cancer

Biological Chemistry ◽

10.1515/hsz-2019-0407 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Zahra Bayat ◽

Zahra Ghaemi ◽

Mehrdad Behmanesh ◽

Bahram M. Soltani

Keyword(s):

Colorectal Cancer ◽

Cell Cycle ◽

Annexin V ◽

Luciferase Assay ◽

Tgfβ Signaling ◽

Normal Tissues ◽

A Cell ◽

Bona Fide ◽

And Migration ◽

Hct116 Cells

Abstract TGFβ signaling is a known pathway to be involved in colorectal cancer (CRC) progression and miRNAs play crucial roles by regulating different components of this pathway. Hence, finding the link between miRNAs and the pathway could be beneficial for CRC therapy. Array data indicated that miR-186-5p is a differentially expressed miRNA in colorectal Tumor/Normal tissues and bioinformatics tools predicted SMAD6/7 (inhibitory SMADs) as bona fide targets of this miRNA. Here, we intended to investigate the regulatory effect of the miR-186-5p expression on TGFβ signaling in CRC. Firstly, the miR-186-5p overexpression in HCT116 cells resulted in a significant reduction of SMAD6/7 expression, measured through RT-qPCR. Then, the direct interactions of miR-186-5p with SMAD6/7 3′UTRs were supported through dual luciferase assay. Furthermore, miR-186-5p overexpression suppressed proliferation, cell viability, and migration while, it increased apoptosis in CRC cells, assessed by cell cycle, MTT, scratch and Annexin V/PI apoptosis assays. Consistently, miR-186-5p overexpression resulted in reduced CyclinD1 protein using western blot, and also resulted in increased P21 and decreased c-Myc expression. Overall, these results introduced miR-186-5p as a cell cycle suppressor through downregulation of SMAD6/7 expression. Thus, miR-186-5p might be served as a novel tumor suppressive biomarker and therapeutic target in CRC treatment.

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Anti-Tumour Effect of Zoledronate in Cells from B Chronic Lymphoytic Leukemia and Low-Grade Lymphoma Patients.

Blood ◽

10.1182/blood.v104.11.4830.4830 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4830-4830

Author(s):

Deborah Vidal Vasconcellos ◽

Karina Lani Silva ◽

Eric Delfraro de Paula Castro ◽

Arthur Coelho Moellman ◽

Maria do Socorro Pombo-de-Oliveira ◽

...

Keyword(s):

Annexin V ◽

Previous Treatment ◽

Lymphocytic Leukemia ◽

Low Grade ◽

Complementary Role ◽

Apoptotic Effect ◽

Previously Treated ◽

Annexin V Assay ◽

Anti Tumour Effect ◽

In Cells

Abstract Recent studies demonstrate that bisphosphonates - anti-resorptive drugs - have direct anti-tumour effect in many tumour cell lines, including hematopoietic ones. The aim of this study was to evaluate the apoptotic effect of Zoledronate in cells from B chronic lymphocytic leukemia (B-CLL) and low-grade lymphoma (LGL) patients. Samples of 19 B-CLL or LGL patients were incubated with Zoledronate 100 μM in RPMI medium supplemented with fetal bovine serum 10% at 370C for 12h. Apoptosis using Annexin V assay, by flow cytometry (FC), was observed in 8 out of 19 (42,1%) patients despite previous treatment. Multidrug resistance (MDR) phenotype was performed using rhodamine-123 efflux assay by FC. Our results demonstrate that Zoledronate 100 m M can induce apoptosis in B malignant lymphocytes despite previous treatment and MDR phenotype. So, patients previously treated with distinct therapeutic agents or not can potentially benefit from the anti-tumour effect of Zoledronate. This is the first work demonstrating the anti-tumour effect of Zoledronate in newly obtained cells from patients with B-CLL and LGL. These results in association with evidences from recent studies suggest that Zoledronate may have an important and complementary role in hematological malignant diseases.

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T3 preserves ovarian granulosa cells from chemotherapy-induced apoptosis

Journal of Endocrinology ◽

10.1530/joe-12-0153 ◽

2012 ◽

Vol 215 (2) ◽

pp. 281-289 ◽

Cited By ~ 23

Author(s):

Cecilia Verga Falzacappa ◽

Eleonora Timperi ◽

Barbara Bucci ◽

Donatella Amendola ◽

Piero Piergrossi ◽

...

Keyword(s):

Cell Cycle ◽

Thyroid Hormone ◽

Granulosa Cells ◽

Lethal Effect ◽

Living Cells ◽

Cell Cycle Distribution ◽

Ovarian Granulosa Cells ◽

A Cell ◽

Induced Apoptosis ◽

Dying Cells

Infertility is a dramatic and frequent side effect in women who are undergoing chemotherapy. Actual strategies are mainly focused on oocyte cryopreservation, but this is not always a suitable option. Considering the key role that granulosa cells play in follicle life, we studied whether thyroid hormone 3,5,3′-triiodothyronine (T3) protects rat ovarian granulosa cells from chemotherapy-induced apoptosis. To this aim, a cell line was established from fresh isolated rat granulosa cells and named rGROV. Cells were exposed to paclitaxel (PTX) and T3, and apoptosis, cell viability, and cell cycle distribution were analyzed under different conditions. First, the integrity of the steroidogenic pathway was demonstrated, and the presence of thyroid receptors, transporters, and deiodinases was confirmed by quantitative PCR. Cells were then exposed to PTX alone or contemporary to T3. MTT and TUNEL assays revealed that while there was a relevant percentage of dying cells when exposed to PTX (40–60%), the percentage was sensibly reduced (20–30%) in favor of living cells if T3 was present. Cell cycle analysis showed that cells exposed to PTX alone were first collected in G2 and then died by apoptosis; on the other hand, the T3 granted the cells to cycle regularly and survive PTX insult. In addition, western blot and FCM analyses confirmed that caspases activation, casp 3 and Bax, were downregulated by T3 and that Bcl2 and cyclins A and B together with cdk1 were upregulated by T3. In conclusion, we demonstrated that thyroid hormone T3 can counteract the lethal effect of taxol on granulosa cells.

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Antibacterial and Cytotoxic Activity of Compounds Isolated fromFlourensia oolepis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/912484 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 18

Author(s):

Mariana Belén Joray ◽

Lucas Daniel Trucco ◽

María Laura González ◽

Georgina Natalia Díaz Napal ◽

Sara María Palacios ◽

...

Keyword(s):

Cell Cycle ◽

Cytotoxic Activity ◽

Lymphoblastic Leukemia ◽

Annexin V ◽

Multidrug Resistant ◽

Leukemic Cells ◽

Cell Cycle Distribution ◽

Cycle Arrest ◽

M Phase ◽

Lower Effect

The antibacterial and cytotoxic effects of metabolites isolated from an antibacterial extract ofFlourensia oolepiswere evaluated. Bioguided fractionation led to five flavonoids, identified as 2′,4′-dihydroxychalcone (1), isoliquiritigenin (2), pinocembrin (3), 7-hydroxyflavanone (4), and 7,4′-dihydroxy-3′-methoxyflavanone (5). Compound1showed the highest antibacterial effect, with minimum inhibitory concentration (MIC) values ranging from 31 to 62 and 62 to 250 μg/mL, against Gram-positive and Gram-negative bacteria, respectively. On further assays, the cytotoxic effect of compounds1–5was determined by MTT assay on acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML) cell lines including their multidrug resistant (MDR) phenotypes. Compound1induced a remarkable cytotoxic activity toward ALL cells (IC50= 6.6–9.9 μM) and a lower effect against CML cells (IC50= 27.5–30.0 μM). Flow cytometry was used to analyze cell cycle distribution and cell death by PI-labeled cells and by Annexin V/PI staining, respectively. Upon treatment,1induced cell cycle arrest in the G2/M phase accompanied by a strong induction of apoptosis. These results describe for the first time the antibacterial metabolites ofF. oolepisextract, with1being the most effective. This chalcone also emerges as a selective cytotoxic agent against sensitive and resistant leukemic cells, highlighting its potential as a lead compound.

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Synergism between Anti-Leukemia Therapeutics and Isoprenoid Pathway Inhibitors in K562 Leukemia Cells.

Blood ◽

10.1182/blood.v108.11.4815.4815 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4815-4815

Author(s):

Eric J. Askeland ◽

Andrew J. Wiemer ◽

Raymond J. Hohl

Keyword(s):

Cell Cycle ◽

Western Blot ◽

Imatinib Mesylate ◽

Annexin V ◽

Cell Cycle Distribution ◽

Isoprenoid Pathway ◽

Apoptotic Proteins ◽

Zaragozic Acid ◽

Digeranyl Bisphosphonate

Abstract Chronic myeloid leukemia (CML) is a consequence of the BCR-ABL oncogene which mediates a phosphorylation cascade of downstream effectors including those of the Ras family. Drugs that target the isoprenoid pathway, such as the farnesyl transferase (FT) inhibitors have shown promise as novel anti-cancer therapies for some hematologic malignancies. Leukemias are treated with specific inhibitors, like imatinib mesylate in the case of CML, and less-specific chemotherapeutic drugs such as the pyrimidine analog cytarabine (ara-C). We systematically evaluated combinations of these and other agents with isoprenoid pathway inhibitors for synergistic anti-leukemia effects. Toxicity was measured in the BCR-ABL-expressing K562 cells using an MTT assay, and drug synergy was assessed using a modified isobologram method. Cell cycle distribution, Annexin-V apoptosis detection, and Western blot analyses were performed on cells treated with synergistic drug combinations. Imatinib mesylate exhibited significant synergy with the squalene synthase inhibitor zaragozic acid, but not with inhibitors for HMG coenzyme A reductase (lovastatin), FPP synthase (zoledronic acid), GGPP synthase (digeranyl bisphosphonate), and FT (alpha-hydroxyfarnesyl phosphonate). Western blot analysis revealed a moderate decrease in Ras protein levels upon treatment with zaragozic acid. This zaragozic acid-mediated decrease in Ras protein may explain the synergy seen between the drugs since imatinib mesylate also affects Ras by decreasing its phosphorylation through inhibition of the BCR-ABL protein. Apoptosis detection and cell cycle distribution did not yield insight into the mechanism underlying this synergy. Ara-C displayed synergy with digeranyl bisphosphonate in the MTT assay. Subsequent cell cycle analysis showed a concentration-dependent G0–G1 arrest by digeranyl bisphosphonate which was enhanced by ara-C. Annexin-V/propidium iodide staining revealed increased cellular apoptosis in response to either digeranyl bisphosphonate or ara-C with synergistic apoptosis to combination treatments. Western blot analysis for anti-apoptotic proteins showed a decrease in Mcl-1 and Bcl-XL protein levels in the presence of digeranyl bisphosphonate. Ara-C has been shown to alter pro-apoptotic and anti-apoptotic proteins in a manner that induces apoptosis. These modifications in pro- and anti-apoptotic proteins and alterations in cell cycling may constitute a mechanism for the synergy seen between digeranyl bisphosphonate and ara-C. Discovery of these synergistic combinations is important because translation of these cell culture results to in vivo testing and human clinical trials may enhance treatment efficacy and diversify available treatment options. Future work will focus on further determining the mechanisms for these synergistic interactions, finding new synergistic combinations, and applying these regimens to in vivo models and clinical trials.

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In Vitro Antigenotoxic, Antihelminthic and Antioxidant Potentials Based on the Extracted Metabolites from Lichen, Candelariella vitellina

Pharmaceutics ◽

10.3390/pharmaceutics12050477 ◽

2020 ◽

Vol 12 (5) ◽

pp. 477 ◽

Cited By ~ 2

Author(s):

Islam El-Garawani ◽

Mahmoud Emam ◽

Waill Elkhateeb ◽

Hesham El-Seedi ◽

Shaden Khalifa ◽

...

Keyword(s):

Cell Cycle ◽

Human Peripheral Blood ◽

Radical Scavenging ◽

Annexin V ◽

Peripheral Blood Lymphocytes ◽

Cell Cycle Distribution ◽

Primary And Secondary Metabolites ◽

Normal Human ◽

Low Cytotoxicity

Lichens have recently received great attention due to their pharmacological potentials. The antigenotoxic potential of C. vitellina extract (25 and 50 µg/mL) was assessed in normal human peripheral blood lymphocytes (HPBL) against Mitomycin C (MMC) co-treatments. Flow cytometric analyses of cell cycle distribution, as well as apoptosis (Annexin V/PI), revealed that the extract had significantly (p ≤ 0.05) ameliorated the MMC toxicity by reducing the apoptotic cells and normalized the cell cycle phases. C. vitellina exhibited antigenotoxicity by ameliorating the diminished mitotic index and DNA single-strand breaks caused by MMC. Herein, the hydromethanolic extract (80%) of Candelariella vitellina (Japan) lichen, exhibited very low cytotoxicity towards normal human peripheral lymphocytes (HPBL) with IC50 >1000 µg/mL. In order to explore the antihelminthic effect, Echinococcus granulosus protoscoleces were used in vitro. Eosin staining revealed significant (p ≤ 0.05) dose and time-dependent scolicidal effects of the extract confirmed by degenerative alterations as observed by electron scan microscopy. Furthermore, primary and secondary metabolites were investigated using GC-MS and qualitative HPLC, revealing the presence of sugars, alcohols, different phenolic acids and light flavonoids. Significant antioxidant capacities were also demonstrated by DPPH radical-scavenging assay. In conclusion, the promising antigenotoxic, antihelminthic and antioxidant potentials of C. vitellina extract encourage further studies to evaluate its possible therapeutic potency.

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Radotinib Enhances Cytarabine (Ara-C)-Induced Acute Myeloid Leukemia Cell Death

10.21203/rs.3.rs-48479/v1 ◽

2020 ◽

Author(s):

Sook-Kyoung Heo ◽

Eui-Kyu Noh ◽

Ho-Min Yu ◽

Do Kyoung Kim ◽

Hye Jin Seo ◽

...

Keyword(s):

Cell Cycle ◽

Cell Death ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Caspase 3 ◽

Annexin V ◽

Chemotherapeutic Agents ◽

Cell Cycle Distribution ◽

Acute Myeloid

Abstract Background: Acute myeloid leukemia (AML) is a heterogeneous disease that frequently relapses after standard chemotherapy. Therefore, there is a need for the development of novel chemotherapeutic agents that could treat AML effectively. Radotinib, an oral BCR-ABL tyrosine kinase inhibitor, was developed as a drug for the treatment of chronic myeloid leukemia. Previously, we reported that radotinib exerts increased cytotoxic effects towards AML cells. However, little is known about the effects of combining radotinib with Ara-C, a conventional chemotherapeutic agent for AML, with respect to cell death and cell cycle distribution in AML cells. Methods: Synergistic anti-cancer effects of radotinib and Ara-C in AML cells including HL60, HEL92.1.7, THP-1 and bone marrow cells from AML patients have been examined. Diverse cell biological assays such as cell viability assay, Annexin V-positive cells, caspase-3 activity, cell cycle distribution, and related signaling pathway have been performed. We also confirmed synergistic effects of radotinib and Ara-C on the xenograft model in vivo. Results: The combination of radotinib and Ara-C was found to induce AML cell apoptosis, which involved the mitochondrial pathway. In brief, combined radotinib and Ara-C significantly induced Annexin V-positive cells, cytosolic cytochrome C, and the pro-apoptotic protein Bax in AML cells including HL60, HEL92.1.7, and THP-1. In addition, mitochondrial membrane potential and Bcl-xl protein were markedly decreased by radotinib and Ara-C. Moreover, this combination induced caspase-3 activity. Cleaved caspase-3, 7, and 9 levels were also increased by combined radotinib and Ara-C. Additionally, radotinib and Ara-C co-treatment induced G0/G1 arrest via the induction of CDKIs such as p21 and p27 and the inhibition of CDK2 and cyclin E. Thus, radotinib/Ara-C induces mitochondrial-dependent apoptosis and G0/G1 arrest via the regulation of the CDKI–CDK–cyclin cascade in AML cells. In addition, our results showed that combined treatment with radotinib and Ara-C inhibits AML cell growth, including tumor volumes and weights in vivo. Also, the combination of radotinib and Ara-C can sensitize cells to chemotherapeutic agents such as daunorubicin or idarubicin in AML cells. Conclusions: Therefore, our results can be concluded that radotinib in combination with Ara-C possesses a strong anti-AML activity.

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