Effect of bixin on DNA damage and cell death induced by doxorubicin in HL60 cell line

2016 ◽  
Vol 35 (12) ◽  
pp. 1319-1327 ◽  
Author(s):  
GC Santos ◽  
MR Almeida ◽  
LMG Antunes ◽  
MLP Bianchi
Keyword(s):  
Dna Damage ◽  
Hl60 Cell ◽  
Red Pigment ◽  
Combined Treatments ◽  
Therapeutic Approaches ◽  
Cytotoxic Effects ◽  
Hl60 Cells ◽  
Apoptotic Effect ◽  
Induction Of Apoptosis ◽  
Hl60 Cell Line

Bixin is a natural red pigment extracted from annatto. Although it is widely used as a coloring agent in food, there are few studies about the effect of this carotenoid on DNA. This study aimed to investigate the effects of bixin on cytotoxicity and genotoxicity induced by doxorubicin in HL60 cells. At concentrations above 0.3 μg/mL, bixin demonstrated cytotoxic effects in HL60 cells. Furthermore, this carotenoid was neither mutagenic nor genotoxic to HL60 cells and reduced the DNA damage induced by doxorubicin. Bixin and doxorubicin showed no apoptotic effect in HL60 cells, but the simultaneous combined treatments showed an increase in the percentage of apoptotic cells. In conclusion, our results showed that bixin modulates the cytotoxicity of doxorubicin via induction of apoptosis. The results of this study provide more knowledge about the toxic effects of anticancer treatments and how the natural compounds can be useful on these therapeutic approaches.

Pisosterol induces interphase arrest in HL60 cells with C-MYC amplification

2010 ◽  
Vol 29 (3) ◽  
pp. 235-240 ◽  
Author(s):  
TCR Silva ◽  
PDL Lima ◽  
MO Bahia ◽  
AS Khayat ◽  
FS Bezerra ◽  
...  
Keyword(s):  
Cell Line ◽  
Hl60 Cell ◽  
Leukaemia Cell Line ◽  
Hl60 Cells ◽  
Anti Cancer ◽  
Before And After ◽  
Myc Gene ◽  
Hl60 Cell Line ◽  
High Degree

The leukaemia cell line HL60 is widely used in studies of the cell cycle, apoptosis and adhesion mechanisms in cancer cells. One marked characteristic of HL60 cells is the C-MYC proto-oncogene amplification, resulting in the formation of homogeneously staining regions (HSRs) at 8p24. We conducted a fluorescence in situ hybridization study in an HL60 cell line, using a locus-specific probe for C-MYC, before and after treatment with pisosterol (at 0.5, 1.0 and 1.8 μg/mL), a triterpene isolated from the fungus Pisolithus tinctorius. Before treatment, 87.5% of the cells showed HSRs. After treatment, no effects were detected at lower concentrations of pisosterol (0.5 and 1.0 μg/mL). However, at 1.8 μg/mL only 15% of the cells presented HSRs, and 39.5% presented few fluorescent signals (3 or 4 alleles), suggesting that pisosterol probably blocks the cells with HSRs at interphase. This result is particularly interesting because cells that do not show a high degree of C-MYC gene amplification have a less aggressive and invasive behaviour and are easy targets for chemotherapy. Therefore, further studies are needed to examine the use of pisosterol in combination with conventional anti-cancer therapy.

Bortezomib Combined with Harringtonine or Arsenious Acid Induced Apoptosis in HL-60 Cells and Its Mechanism.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4412-4412
Author(s):  
Fan Yi Meng ◽  
Yun-bi Fu ◽  
Qi-xin Sun ◽  
Jun Xie ◽  
Guang-biao Zhou
Keyword(s):  
Western Blotting ◽  
Caspase 3 ◽  
Hl60 Cell ◽  
Caspase 9 ◽  
Hl60 Cells ◽  
Arsenious Acid ◽  
Associated Proteins ◽  
Induced Apoptosis ◽  
Hl60 Cell Line ◽  
Combined Drugs

Abstract Objective: To explore the apoptosis effect induced by bortezomib combined with harringtonine or arsenious acid in HL60 cell line and the mechanism. Methods: Cell’s apoptosis was demonstrated by MTT assay and Hoechst33342 staining. Expression of Bcl-2, Caspase-9, Caspase-3 and PARP protein was detected by western blotting. Results: HL60 cells’ apoptosis could be induced by bortezomib, harringtonine and arsenious acid respectively, and the apoptosis effect was inhanced significantly when bortezomib combined with harringtonine or arsenious acid. Western blotting showed Bcl-2 protein was down-regulated and Caspase-9, Caspase-3 and PARP proteins were all cleaved activation when cells were treated by 15uM arsenious acid alone, but only cleaved activation of PARP and down-regulation of Bcl-2 protein be detected when cells were treated with 30nM harringtonine alone, expression of Caspase-9 and Caspase-3 has no change compared with the control. The changes of associated proteins were paralleled with the cell’s apoptosis when treated with combined drugs. Conclusion: HL60 cells’ apoptosis could be inhanced significantly when treated by bortezomib combined with harringtonine or arsenious acid compared with treated by bortezomib alone. Arsenious acid and bortezomib can inhibit caspase signaling pathway and down-regulate the expression of Bcl-2 protein together, but harringtonine and bortezomib can only down-regulate the expression of Bcl-2 protein and induce cleaved activation of PARP together.

Expression of the DNA Repair Gene RAD51 Is Associated with FLT3 ITD Transcript Level and Is Down-Regulated by PKC412 Resulting in Suppression of DNA Repair.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 283-283
Author(s):  
Claire H. Seedhouse ◽  
Hannah M. Hunter ◽  
Ian Carter ◽  
Anne-Marie Massip ◽  
Monica Pallis ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Cell Line ◽  
Mammalian Cells ◽  
Transcript Level ◽  
Hl60 Cell ◽  
Prognostic Impact ◽  
Dna Repair Gene ◽  
Increased Risk ◽  
Hl60 Cell Line

Abstract The presence of internal tandem duplication (ITD) mutations in the FLT3 receptor tyrosine kinase confer an adverse prognosis in AML due to an increased risk of disease relapse. However the mechanisms underlying this increased relapse risk are unclear. We have investigated whether AML cells with FLT3 ITD mutations have an enhanced capacity for DNA repair following cytotoxic drug exposure. RAD51 is a key protein in the high-fidelity homologous recombination double strand break repair pathway and is the limiting factor for this pathway in mammalian cells. Using quantitative real-time PCR we found that the level of RAD51 transcripts are significantly correlated with the level of FLT3 transcripts in FLT3 ITD cells (n=27; p=0.017) but not in FLT3 WT cells (n=57; p=0.58). Clinically FLT3 ITDs have the most significant prognostic impact in AML patients with normal cytogenetics and if this group is studied the association between FLT3 ITD and RAD51 transcript levels are particularly pronounced (n=12; p=0.003). To establish whether increases in RAD51 expression correlate with enhanced DNA repair activity we have adopted the comet assay and studied the MV4-11 cell line (FLT3 ITD), HL60 cell line (FLT3 WT) and a number of AML patient cells. The background level of DNA damage in untreated FLT3 ITD AML patients and the MV4-11 cell line was significantly lower than in FLT3 WT patients and the HL60 cell line (n=10; p=0.02), suggesting a constitutive up-regulation of DNA repair in cells harbouring the FLT3 ITD mutation resulting in lower background levels of DNA damage. To test whether the increase in RAD51 and DNA repair was a consequence of the FLT3 ITD, we treated cells with the FLT3 inhibitor PKC412 and then examined the response of the cells to sub-toxic doses of daunorubicin. The MV4-11 FLT3 ITD cells, but not the FLT3 WT HL60 cells, demonstrated a statistically significant suppression of early DNA repair when treated with PKC412 and daunorubicin (p<0.001). Similar results were obtained in primary AML cells, with a loss of early DNA repair in the FLT3 ITD cells and no effect on the WT FLT3 cells. Furthermore the reduction in daunorubicin-induced DNA repair seen in PKC412 treated FLT3 ITD cells was associated with down-regulation of RAD51 expression. There was a statistically significant decrease in RAD51 transcript level following PKC412 treatment in the FLT3 ITD patients and MV4-11 cell line but not in the FLT3 WT patients or HL60 cell line (p<0.05). The decrease in the expression of RAD51 is closely associated with the reduction in DNA repair function in the inhibitor treated FLT3 ITD cells. This work suggests that high expression levels of FLT3 transcripts in AML cells with a FLT3 ITD up-regulate RAD51 resulting in more efficient DNA repair following chemotherapy treatment. This may lead to resistance to cytotoxic therapies and genomic instability, ultimately resulting in the manifestation of a more resistant disease and a greater likelihood of relapse. The use of FLT3 inhibitors concurrently with or following AML therapy may suppress enhanced DNA repair in FLT3 mutated cells.

scholarly journals Cytotoxic and Apoptotic Effects of Different Extracts ofArtemisia turanicaKrasch. on K562 and HL-60 Cell Lines

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Zahra Tayarani-Najaran ◽  
Mahla Sareban ◽  
Atefeh Gholami ◽  
Seyed Ahmad Emami ◽  
Mahdi Mojarrab
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Cytotoxic Activities ◽  
Cytotoxic Effects ◽  
Normal Cells ◽  
Resazurin Assay ◽  
Apoptotic Effect ◽  
Induction Of Apoptosis ◽  
Apoptotic Effects

Artemisiais an important genus of Iranian flora. Cytotoxic activities for some species of the genus have already been reported. In this study, we have investigated the cytotoxic effects ofn-hexane, CH2Cl2, EtOAc, EtOH, and EtOH/H2O (1 : 1) extracts ofA. turanicaKrasch. on two human leukemic cancer cell lines (K562 and HL-60) and J774 as normal cells using alamarBlue (resazurin) assay. PI staining of the fragmented DNA and western blot analysis were used to evaluate the possible apoptotic effect of the extract. The CH2Cl2extract ofA. turanicashowed the most antiproliferative effect on cancer cells among all tested extracts with IC50values of 69 and 104 μg/mL on K562 and HL-60 cells, respectively, whereas the normal cells were not affected significantly by this extract. Sub-G1 peak in the flow cytometry histogram of the cells treated with CH2Cl2extract ofA. turanicaand cleavage of PARP protein confirmed the induction of apoptosis with CH2Cl2extract. Taken together, the findings of the present work suggest the anticancer potential of CH2Cl2extract ofA. turanicaon human leukemic cancer cell lines.

scholarly journals Apoptosis mediated chemosensitization of tumor cells to 5-fluorouracil on supplementation of fish oil in experimental colon carcinoma

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769501 ◽  
Author(s):  
Isha Rani ◽  
Bhoomika Sharma ◽  
Sandeep Kumar ◽  
Satinder Kaur ◽  
Navneet Agnihotri
Keyword(s):  
Fatty Acids ◽  
Dna Damage ◽  
Polyunsaturated Fatty Acids ◽  
Fish Oil ◽  
Tumor Cells ◽  
Apoptotic Index ◽  
Apoptotic Pathway ◽  
Apoptotic Effect ◽  
Underlying Mechanisms ◽  
Apoptotic Pathways

5-Fluorouracil has been considered as a cornerstone therapy for colorectal cancer; however, it suffers from low therapeutic response rate and severe side effects. Therefore, there is an urgent need to increase the clinical efficacy of 5-fluorouracil. Recently, fish oil rich in n-3 polyunsaturated fatty acids has been reported to chemosensitize tumor cells to anti-cancer drugs. This study is designed to understand the underlying mechanisms of synergistic effect of fish oil and 5-fluorouracil by evaluation of tumor cell–associated markers such as apoptosis and DNA damage. The colon cancer was developed by administration of N,N-dimethylhydrazine dihydrochloride and dextran sulfate sodium salt. Further these animals were treated with 5-fluorouracil, fish oil, or a combination of both. In carcinogen-treated animals, a decrease in DNA damage and apoptotic index was observed. There was also a decrease in the expression of Fas, FasL, caspase 8, and Bax, and an increase in Bcl-2. In contrast, administration of 5-fluorouracil and fish oil as an adjuvant increased both DNA damage and apoptotic index by activation of both extrinsic and intrinsic apoptotic pathways as compared to the other groups. The increased pro-apoptotic effect by synergism of 5-fluorouracil and fish oil may be attributed to the incorporation of n-3 polyunsaturated fatty acids in membrane, which alters membrane fluidity in cancer cells. In conclusion, this study highlights that the induction of apoptotic pathway by fish oil may increase the susceptibility of tumors to chemotherapeutic regimens.

scholarly journals Bis[Pyrrolyl Ru(II)] Triads: a New Class of Photosensitizers for Metal-Organic Photodynamic Therapy

2020 ◽  
Author(s):  
Deborah A. Smithen ◽  
Susan Monro ◽  
Mitch Pinto ◽  
John A. Roque III ◽  
Roberto M. Diaz-Rodriguez ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Visible Light ◽  
Red Light ◽  
Visible Region ◽  
Hl60 Cell ◽  
Quantum Yields ◽  
Human Leukemia ◽  
New Family ◽  
Hl60 Cell Line

A new family of ten dinuclear Ru(II) complexes based on the bis[pyrrolyl Ru(II)] triad scaffold, where two Ru(bpy)<sub>2</sub> centers are separated by a variety of organic linkers, was prepared to evaluate the influence of the organic chromophore on the spectroscopic and in vitro photodynamic therapy (PDT) properties of the compounds. The bis[pyrrolyl Ru(II)] triads absorbed strongly throughout the visible region, with several members having molar extinction coefficients (e) ≥10<sup>4</sup> at 600–620 nm and longer. Phosphorescence quantum yields were generally less than 0.1% and in some cases undetectable. The singlet oxygen quantum yields ranged from 5% to 77% and generally correlated with their photocytotoxicities toward human leukemia (HL-60) cells regardless of the wavelength of light used. Dark cytotoxicities varied ten-fold, with EC<sub>50</sub> values in the range of 10–100 µM and phototherapeutic indices (PIs) as large as 5,400 and 260 with broadband visible (28 J cm<sup>-2</sup>, 7.8 mW cm<sup>-2</sup>) and 625-nm red (100 J cm<sup>-2</sup>, 42 mW cm<sup>-2</sup>) light, respectively. The bis[pyrrolyl Ru(II)] triad with a pyrenyl linker (5h) was especially potent, with an EC50 value of 1 nM and PI >27,000 with visible light and subnanomolar activity with 625-nm light (100 J cm<sup>-2</sup>, 28 mW cm<sup>-2</sup>). The lead compound 5h was also tested in a tumor spheroid assay using the HL60 cell line and exhibited greater photocytotoxcicity in this more resistant model (EC<sub>50</sub>=60 nM and PI>1,200 with 625-nm light) despite a lower dark cytotoxicity. The in vitro PDT effects of 5h extended to bacteria, where submicromolar EC<sub>50</sub> values and PIs >300 against <i>S. mutans</i> and <i>S. aureus </i>were obtained with visible light. This activity was attenuated with 625-nm red light, but PIs were still near 50. The ligand-localized <sup>3</sup>ππ* state contributed by the pyrenyl linker of 5h likely plays a key role in its phototoxic effects toward cancer cells and bacteria.<br><br>

scholarly journals Induction of apoptosis and ferroptosis by a tumor suppressing magnetic field through ROS-mediated DNA damage

Aging ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 3662-3681 ◽  
Author(s):  
Lin-Qing Yuan ◽  
Can Wang ◽  
Dong-Fang Lu ◽  
Xia-Di Zhao ◽  
Lin-Hua Tan ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Dna Damage ◽  
Induction Of Apoptosis

scholarly journals Down-Regulation of Interleukin-8 Gene Expression in HL60 Cell Line by Human Kunitz-Type Trypsin Inhibitor

1995 ◽  
Vol 206 (3) ◽  
pp. 927-934 ◽  
Author(s):  
K. Maehara ◽  
N. Kanayama ◽  
A. Halim ◽  
E. Elmaradny ◽  
T. Oda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Line ◽  
Trypsin Inhibitor ◽  
Interleukin 8 ◽  
Hl60 Cell ◽  
Down Regulation ◽  
Kunitz Type ◽  
Hl60 Cell Line

scholarly journals Molecular Mechanisms of Zinc Oxide Nanoparticle-Induced Genotoxicity

Materials ◽  
2017 ◽  
Vol 10 (12) ◽  
pp. 1427 ◽  
Author(s):  
Agmal Scherzad ◽  
Till Meyer ◽  
Norbert Kleinsasser ◽  
Stephan Hackenberg
Keyword(s):  
Dna Damage ◽  
Zinc Oxide ◽  
Mammalian Cells ◽  
Oxidative Dna Damage ◽  
Molecular Mechanisms ◽  
Consumer Products ◽  
Zno Nps ◽  
Cytotoxic Effects

Background: Zinc oxide nanoparticles (ZnO NPs) are among the most frequently applied nanomaterials in consumer products. Evidence exists regarding the cytotoxic effects of ZnO NPs in mammalian cells; however, knowledge about the potential genotoxicity of ZnO NPs is rare, and results presented in the current literature are inconsistent. Objectives: The aim of this review is to summarize the existing data regarding the DNA damage that ZnO NPs induce, and focus on the possible molecular mechanisms underlying genotoxic events. Methods: Electronic literature databases were systematically searched for studies that report on the genotoxicity of ZnO NPs. Results: Several methods and different endpoints demonstrate the genotoxic potential of ZnO NPs. Most publications describe in vitro assessments of the oxidative DNA damage triggered by dissoluted Zn2+ ions. Most genotoxicological investigations of ZnO NPs address acute exposure situations. Conclusion: Existing evidence indicates that ZnO NPs possibly have the potential to damage DNA. However, there is a lack of long-term exposure experiments that clarify the intracellular bioaccumulation of ZnO NPs and the possible mechanisms of DNA repair and cell survival.

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