scholarly journals Antimutagenic and Synergistic Cytotoxic Effect of Cisplatin and Honey Bee Venom on 4T1 Invasive Mammary Carcinoma Cell Line

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Faranak Shiassi Arani ◽  
Latifeh Karimzadeh ◽  
Seyed Mohammad Ghafoori ◽  
Mohammad Nabiuni
Keyword(s):  
Cell Death ◽  
Cell Line ◽  
Honey Bee ◽  
Mtt Assay ◽  
Mammary Carcinoma ◽  
Ames Test ◽  
Cytotoxic Effect ◽  
Bee Venom ◽  
Antimutagenic Activity ◽  
Dependent Manner

Introduction. Honey bee venom (HBV) has various biological activities such as the inhibitory effect on several types of cancer. Cisplatin is an old and potent drug to treat most of the cancers. Our aim in the present study was to determine antimutagenic and cytotoxic effects of HBV on mammary carcinoma, exclusively and in combination with cisplatin. Methods. In this study, 4T1 cell line was cultured in RPMI-1640 with 10% fetal bovine serum (FBS), at 37°C in humidified CO2 incubator. The cell viabilities were examined by the MTT assay. Also, HBV was screened‏ for its antimutagenic activity via the Ames test. The results were assessed by SPSS software version 19 and one-way ANOVA method considering p<0.05 level of significance. Results. The results showed that 6 mg/ml of HBV, 20 μg/ml of cisplatin, and 6 mg/ml HBV with 10 μg/ml cisplatin could induce approximately 50% of 4T1 cell death. The concentration 7 mg/ml of HBV with of 62.76% inhibitory rate showed the highest antimutagenic activity in comparison with other treatment groups. Conclusions. The MTT assay demonstrated that HBV and cisplatin could cause cell death in a dose-dependent manner. The cytotoxic effect of cisplatin also promoted by HBV. Ames test outcomes indicated that HBV could act as a significant mutagenic agent. The antimutagenic activity of HBV was increased considerably in the presence of S9 mix. Therefore, our findings have revealed that HBV can enhance the cytotoxic effect of cisplatin drug and its cancer-preventing effects.

scholarly journals Anti-mutagenic and synergistic cytotoxic effect of cisplatin and Honey Bee venom on 4T1 invasive mammary carcinoma cell line

2017 ◽  
Author(s):  
Faranak Shiassi Arani ◽  
Latifeh Karimzadeh ◽  
Seyed Mohammad Ghafoori ◽  
Mohammad Nabiuni
Keyword(s):  
Cell Death ◽  
Cell Line ◽  
Honey Bee ◽  
Mtt Assay ◽  
Sodium Azide ◽  
Mammary Carcinoma ◽  
Ames Test ◽  
Cytotoxic Effect ◽  
Mutagenic Activity ◽  
Bee Venom

ABSTRACTHoney Bee Venom has various biological activities such as inhibitory effect on several types of cancer. Cisplatin is an old and potent drug to treat the most of cancer. Our aims in this study were determination of the anti-mutagenic and cytotoxic effects of HBV on mammary carcinoma, lonely and in combination with cisplatin. In this study 4T1 cell line were cultured and incubated at 37 C in humidified CO2-incubator. The cell viabilities were examined by MTT assay. Also HBV was screened for its anti-mutagenic activity against sodium azide by Ames test. The result showed that 6μg/ml HBV, 20μg/ml cisplatin and 6μg/ml HBV with 10μg/ml cisplatin can induce an approximately 50% 4T1 cell death. 7mg/ml HBV with the inhibition of 62.76% sodium azide showed high potential in decreasing the mutagenic agents. MTT assay demonstrated that HBV and cisplatin can cause cell death in a dose-dependent manner. The cytotoxic effect of cisplatin is also promoted by HBV. Ames test results indicated that HBV can inhibit sodium azide as a mutagenic agent. Anti-mutagenic activity of HBV was increased significantly in presence of S9 mix. Hence, our findings reveal that HBV can enhance the cytotoxic effect of cisplatin drug and it has cancer preventing effects.

scholarly journals Antioxidant and Proapoptotic Activities ofSclerocarya birrea[(A. Rich.) Hochst.] Methanolic Root Extract on the Hepatocellular Carcinoma Cell Line HepG2

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Maria Francesca Armentano ◽  
Faustino Bisaccia ◽  
Rocchina Miglionico ◽  
Daniela Russo ◽  
Nicoletta Nolfi ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Line ◽  
Hepg2 Cells ◽  
Cytotoxic Effect ◽  
Antioxidant Activities ◽  
Dermal Fibroblasts ◽  
Root Extract ◽  
Dependent Manner ◽  
Mitochondrial Membrane Depolarization

The main goal of this study was to characterize thein vitroantioxidant activity and the apoptotic potential ofS. birreamethanolic root extract (MRE). Among four tested extracts, obtained with different solvents, MRE showed the highest content of polyphenols, flavonoids, and tannins together with antioxidant activities tested with superoxide, nitric oxide, ABTS, and beta-carotene bleaching assays. Moreover, the cytotoxic effect of MRE was evaluated on the hepatocarcinoma cell line HepG2. In these cells, MRE treatment induced apoptosis and generated reactive oxygen species (ROS) in dose-dependent manner. The cytotoxic effect promoted by MRE was prevented by pretreatment of HepG2 cells with N-acetyl-L-cysteine (NAC), suggesting that oxidative stress was pivotal in MRE-mediated cell death. Moreover, we showed that the MRE treatment induced the mitochondrial membrane depolarization and the cytochromecrelease from mitochondria into the cytosol. It suggests that the apoptosis occurred in a mitochondrial-dependent pathway. Interestingly, MRE showed a sensibly lower cytotoxicity, associated with a low increase of ROS, in normal human dermal fibroblasts compared to HepG2 cells. It is suggested that the methanolic root extract ofS. Birreais able to selectively increase intracellular ROS levels in cancer cells, promoting cell death.

Honey Bee Dry Venom Reduces Hepatitis B Virus Surface Antigen Secretion in PLC/PRF/5 Cell Line

2019 ◽  
Author(s):  
Hussein Khani ◽  
Mahdi Ghorbani ◽  
Farshad Nojoomi ◽  
Alireza Mohebbi
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Cell Line ◽  
Honey Bee ◽  
Surface Antigen ◽  
Post Treatment ◽  
Bee Venom ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
B Virus

Background and Aims: Currently, many efforts are directed toward functional Hepatitis B virus (HBV) treatment. This is achievable by suppression of HBV surface antigen (HBsAg) secretion. In this regard, use of natural products has been the areas of interest by scientific communities.  Materials and Methods: Dried Honey Bee venom was extracted for assessing its anti-HBsAg secretion potential. Hepatoma cell-derived PLC/PRF/5 was propagated in complete medium. The cell line was treated by a serial dilution of Bee venom. Cell cytotoxicity (IC50) was measured by MTT colorimetric assay at three post-treatment times. HBsAg secretion was evaluated from PLC/PRF/5 supernatant treated by under-cytotoxic concentrations of Bee venom by using enzyme-linked immunosorbent assay.  Results: The results indicated that dried Bee venom extract is able to reduce secretion of HBsAg from the cell line with Selectivity Index (SI) of eight. Reduced levels of HBsAg were in dose-dependent manner and it was in its lower concentrations at 8 ppm after 12 hr post treatment. The IC50 was observed to be 63.78 ppm. Conclusions: The Bee venom has anti-HBV activity. The way we used under-cytotoxic concentration of Bee venom, the HBsAg secretion was restored after 24 hr post treatment. Furthermore, mechanism of action of Bee venom in reducing HBsAg level needs to be further investigated.

Antiproliferative and Apoptotic Properties of Andrographolide Against Human Colon Cancer DLD1 Cell Line

2020 ◽  
Vol 20 (6) ◽  
pp. 930-942 ◽  
Author(s):  
Imran Khan ◽  
Sadaf Mahfooz ◽  
Irfan A. Ansari
Keyword(s):  
Colon Cancer ◽  
Cell Line ◽  
Mtt Assay ◽  
Caspase 3 ◽  
Chemotherapeutic Agents ◽  
Synergistic Activity ◽  
Dependent Manner ◽  
Apoptosis Induction ◽  
Dld1 Cell ◽  
Activation Assay

Background: In recent years, natural products have received great attention for cancer prevention owing to their various health benefits, noticeable lack of toxicity and side effects, and the limitations of chemotherapeutic agents. Andrographolide, a labdane diterpenoid is a principal bioactive constituent of Andrographis paniculata Nees, exhibits significant anticancer activity. Objective: The efficacy of andrographolide on colon cancer cells is yet to be elucidated completely. Therefore, we investigated the anticancer efficiency of andrographolide in colon cancer DLD1 cell line. Methods: Antiproliferative activity of andrographolide on DLD1 cells was evaluated by MTT assay, LDH release assay, morphological analysis and colony formation assay. Induction of apoptosis was determined by DAPI staining, Annexin V-FITC staining assay, and caspase-3 activation assay. Role of andrographolide induced cellular reactive oxygen species (ROS) and its association with apoptosis induction in DLD1 cells was elucidated by DCFDA dye. Synergistic ability of andrographolide with 5- fluorouracil (5-FU) and paclitaxel (PTX) was evaluated by MTT assay. Results: Results of the present study indicated that andrographolide declined cell viability of DLD1 cells in a concentration and time-dependent manner. Andrographolide induced apoptosis via nuclear condensation, phosphatidylserine externalization and caspase-3 activation. It also augmented cellular ROS levels which were in turn associated with apoptosis induction in DLD1 cells. Moreover, andrographolide displayed synergistic activity with 5-FU and PTX against DLD1 cells. Conclusion: The present study showed that andrographolide demonstrated antiproliferative and apoptotic properties, moreover it also displayed synergistic effect with chemotherapeutic drugs in colon cancer DLD1 cells.

scholarly journals In vitro cytotoxic study for partially purified resveratrol extracted from grape skin fruit Vitis vinifera

2009 ◽  
Vol 3 (2) ◽  
pp. 40-47
Author(s):  
Zainab Y. Mohammed ◽  
Essam F. Al-Jumaily ◽  
Nahi Y. Yaseen
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Cytotoxic Effect ◽  
Inhibitory Effect ◽  
Mammary Adenocarcinoma ◽  
Dependent Manner ◽  
Grape Skin ◽  
Grape Fruit ◽  
Glass Column

The partial purified resveratrol was obtained from the skin of black grape fruit cultivated in Iraq using 80% ethanolic solution, then an acid hydrolysis with 10% HCl solution for (10–30) min at 60Cº was carried out. The aglycone moiety was taken with an organic solvent (chloroform), then using an open glass column packed with silica gelG 60 as a stationary phase and a mobile phase of; benzene: methanol: actic acid (20:4:1). The study utilized an in vitro evaluation for the cytotoxic effect of the partially purified resveratrol on some cell lines including, the murine mammary adenocarcinoma (Ahmed –Mohammed –Nahi–2003 -AMN -3) cell line; the human laryngeal carcinoma (Hep -2) cell line and the Rat Embryo Fibroblast (REF) cell line at different concentrations and different exposure time of treatment. The partial purified resveratrol extract concentrations ranging (7.8–4000) µg/ml in a two fold serial dilutions were used to treat the three types of cell lines for 48 and 72 hours intervals. AMN-3 cell lines showed highest sensitivity toward the cytotoxic effect of the paritial purified resveratrol than other cell lines after 48 hours in a dose dependent manner. While Hep-2 cell line showed novel behavior, the lowest concentration of cell treatment gave the most significant (P< 0.01) inhibitory effect. Only the highest concentration gave significant inhibitory effect (P< 0.01) with the transformed Ref cell line.

scholarly journals Effect of Calomelanone, a Dihydrochalcone Analogue, on Human Cancer Apoptosis/Regulated Cell Death in an In Vitro Model

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Wasitta Rachakhom ◽  
Ratana Banjerdpongchai
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Hepg2 Cells ◽  
Cytotoxic Effect ◽  
Human Cancer ◽  
Autophagic Flux ◽  
Dependent Manner ◽  
Anticancer Activities ◽  
Human Cancer Cells ◽  
Regulated Cell Death

Calomelanone, 2 ′ ,6 ′ -dihydroxy-4,4 ′ -dimethoxydihydrochalcone, possesses anticancer activities. This study was conducted to investigate the cytotoxic effect of calomelanone, a dihydrochalcone analogue, on human cancer cells and its associated mechanisms. The cytotoxic effect of calomelanone was measured by MTT assay. Annexin V-FITC/propidium iodide and DiOC6 staining that employed flow cytometry were used to determine the mode of cell death and reduction of mitochondrial transmembrane potential (MTP), respectively. Caspase activities were measured using specific substrates and colorimetric analysis. The expression levels of Bcl-2 family proteins were determined by immunoblotting. Reactive oxygen species were also measured using 2 ′ ,7 ′ -dihydrodichlorofluorescein diacetate and dihydroethidium (fluorescence dyes). Calomelanone was found to be toxic towards various human cancer cells, including acute promyelocytic HL-60 and monocytic leukemic U937 cells, in a dose-dependent manner at 24 h and human hepatocellular HepG2 cells at 48 h. However, the proliferation of HepG2 cells increased at 24 h. Calomelanone was found to induce apoptosis in HL-60 and U937 at 24 h and HepG2 apoptosis at 48 h via the intrinsic pathway by inducing MTP disruption. This compound also induced caspase-3, caspase-8, and caspase-9 activities. Calomelanone upregulated proapoptotic Bax and Bak and downregulated antiapoptotic Bcl-xL proteins in HepG2 cells. Moreover, signaling was also associated with oxidative stress in HepG2 cells. Calomelanone induced autophagy at 24 h of treatment, which was evidenced by staining with monodansylcadaverine (MDC) to represent autophagic flux. This was associated with a decrease of Akt (survival pathway) and an upregulation of Atg5 (the marker of autophagy). Thus, calomelanone induced apoptosis/regulated cell death in HL-60, U937, and HepG2 cells. However, it also induced autophagy in HepG2 depending on duration, dose, and type of cells. Thus, calomelanone could be used as a potential anticancer agent for cancer treatment. Nevertheless, acute and chronic toxicity should be further investigated in animals before conducting investigations in human patients.

scholarly journals St. John’s Wort Suppresses Growth in Triple-Negative Breast Cancer Cell Line MDA-MB-231 by Inducing Prodeath Autophagy and Apoptosis

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3175
Author(s):  
Mikyoung You ◽  
Young-Hyun Lee ◽  
Hwa-Jin Kim ◽  
Ji Hyun Kook ◽  
Hyeon-A Kim
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cell Line ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Apoptotic Cell ◽  
Cancer Cell Line ◽  
Dependent Manner ◽  
St John’S Wort ◽  
St John's Wort

The rational regulation of programmed cell death by means of autophagy and apoptosis has been considered a potential treatment strategy for cancer. We demonstrated the inhibitory effect of St. John’s Wort (SJW) on growth in the triple-negative breast cancer (TNBC) cell line and xenografted mice and its target mechanism concerning autophagic and apoptotic cell death. SJW ethanol extract (SJWE) inhibited proliferation in a dose-dependent manner. SJWE treatment dramatically increased autophagy flux and apoptosis compared with the control. The autophagy inhibitor, 3-methyladenine (3-MA), reversed the SJWE-induced inhibition of cell proliferation and regulation of autophagy and apoptosis, indicating that SJWE induced apoptosis through prodeath autophagy. Furthermore, SJWE inhibited tumor growth and induced autophagy and apoptosis in the tumor of MDA-MB-231 xenografted athymic nude mice. Our results indicate that SJWE might have great potential as a new anticancer therapy for triple-negative breast cancer by inducing prodeath autophagy and apoptosis.

scholarly journals Apoptotic Effect of Melittin Purified from Iranian Honey Bee Venom on Human Cervical Cancer HeLa Cell Line

2017 ◽  
Vol 24 (4) ◽  
pp. 563-570 ◽  
Author(s):  
Hannaneh Zarrinnahad ◽  
Amir Mahmoodzadeh ◽  
Monireh Parviz Hamidi ◽  
Mehdi Mahdavi ◽  
Ali Moradi ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Hela Cell ◽  
Cell Line ◽  
Honey Bee ◽  
Bee Venom ◽  
Hela Cell Line ◽  
Apoptotic Effect ◽  
Human Cervical Cancer

A Novel Pan-PI3K/Akt Inhibitor, SF1126, Inhibits In Vitro Growth of Multiple Myeloma Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4806-4806
Author(s):  
Jeannine Silberman ◽  
Kimberly Dalbey ◽  
Claire Torre ◽  
Ebenezer David ◽  
Leif Bergsagel ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Death ◽  
Growth Inhibition ◽  
Cell Line ◽  
Cell Lines ◽  
Mtt Assay ◽  
Immunoblot Analysis ◽  
Akt Inhibitor ◽  
Downstream Targets

Abstract Backround: Dysregulation of the PI3K/Akt signal transduction pathway has been implicated in the development of a number of malignancies, including multiple myeloma (MM). This cellular signaling mechanism and its downstream targets (eg mTOR) regulate cell growth, proliferation and apoptosis. SF1126 (Semafore) is a water soluble prodrug of the pan-PI3K inhibitor, LY294002, whose anti-proliferative and pro-apoptotic activity has been well described in the literature. Preclinical studies using SF1126 in a variety of malignancies including glioma, prostate, non-small cell lung cancer, and breast cancer appear promising and have demonstrated profound antiangiogenic effects mediated through VEGF inhibition. Aim: To demonstrate in vitro anti-myeloma activity of SF1126, alone and in combination with dexamethasone, bortezomib, and melphalan and evaluate their effects on downstream targets of PI3K/Akt. Methods: MM cell lines (MM.1R, MM.1S, RPMI 8226) were treated with SF1126 (1–100uM), dexamethasone (5uM), bortezomib (5nM), melphalan (10uM) alone, and in combination. Growth inhibition following treatment was measured by MTT assay at 24 and 48 hours. Apoptosis was assessed by annexin-V binding assay using flow cytometry. Immunoblot analysis was performed to measure downstream targets of Akt including: p-PDK1 and mTOR (4E-BP1). Results: A clear dose response was established with an IC50 of 8.75uM in the MM.1R and 7.5uM in the MM.1S cell lines at 48 hours. At 24 and 48 hours, 5uM SF1126 alone resulted in 80% and 64% cell viability by MTT assay, respectively, in the MM.1R cell line. The combination of 5uM SF1126 with conventional agents was then tested in the MM.1R cell line. Combination with 5uM dexamethasone enhanced the efficacy of 5uM SF1126 by 26% at 48 hours. Combination with 10uM melphalan enhanced the efficacy of 5uM SF1126 by 20% at 24 hours. The combination with 5nM bortezomib enhanced the efficacy of 5uM SF1126 by 23% at 48 hours. Given prior experience demonstrating that short exposure to bortezomib activates Akt, we tested sequential administration of bortezomib and SF1126 in the MM.1R cell line. Optimal cell death was induced with bortezomib prior to SF1126, followed by concurrent administration. Immunoblot analysis of p-PDK1, downstream mTOR target (4E-BP1) were performed on the MM.1S cell line treated with 5, 10, 20, and 50uM SF1126 at 12 and 24 hours. At the 12 hour time point, p-PDK-1 appeared to increase, but was significantly reduced by 48 hours. A similar pattern of initial upregulation followed by reduction by 24 hours was seen with the mTOR protein 4E-BP1. Conclusion: SF1126 has dose dependent, in vitro activity in several multiple myeloma cell lines both as a single agent and in combination with dexamethasone, bortezomib, and melphalan. The addition of SF1126 to dexamethasone in a dexamethasone resistant cell line results in increased cell death, possibly by overcoming resistance mechanisms. The addition of SF1126 to bortezomib and melphalan also resulted in increased growth inhibition over either agent alone. These results warrant further study of this promising new pan-PI3K/Akt inhibitor.

scholarly journals Selective Death of Leukemia Initiating Cells Induced By Deferasirox

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 581-581 ◽  
Author(s):  
Saar Shapira ◽  
Pia Raanani ◽  
Arnon Nagler ◽  
Ido Lubin ◽  
Nadir Arber ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Line ◽  
Progenitor Cells ◽  
Cytotoxic Effect ◽  
Conflicts Of Interest ◽  
Remission Rate ◽  
Iron Chelator ◽  
Inhibition Of Proliferation ◽  
Apoptotic Effect ◽  
Cell Fractions

Abstract Despite high remission rate after therapy, only 30-40% of acute myeloid leukemia (AML) patients survive 5 years after diagnosis. The main cause of treatment failure is thought to be insufficient eradication of leukemia initiating cells (LIC). Identifying drugs that can efficiently eradicate LICs is therefore imperative. HIF1α is essential for LIC maintenance and targeting HIF1α selectively eliminates LIC. Deferasirox is an iron chelator used to reduce chronic iron overload in patients receiving long-term blood transfusions. Our aim is to study the ability ofdeferasirox to induce apoptosis and to target HIF1α in AML LICs. CD34+CD38- LIC-like cells, sorted from the KG1a cell line, exhibited increased sensitivity to deferasirox with an IC50 of 1.3μM compared to 8.9μM calculated for the more mature CD34+CD38+ cells. The LIC-like cells, which were more sensitive to deferasirox, were less sensitive to ARA-C compared to the CD34+CD38+ cells. Deferasirox was >2-fold more efficient in inducing apoptosis in the CD34+CD38− cells, compared to the CD34+CD38+ cells (74±7.2% & 32±6.2% apoptosis, respectively). Deferasirox demonstrated a synergistic cytotoxic effect with ARA-C on both the CD34+CD38− and CD34+CD38+ KG1a cell fractions. Similar results were observed with CD34+CD38-CD123+ LICs and CD34+CD38+ CD123+ progenitor cells isolated from AML patients. As shown with the cell line, AML patient LICs were 2-fold more sensitive to deferasirox treatment showing a 62±15% induction of cell death compared to only a 34±9% induction in leukemic progenitor cell death (p<0.01). The increase in cell death was accompanied by an increment of reactive oxygen species (ROS) levels which was more prominent in the LICs compared to the progenitor cells. Furthermore, deferasirox enhanced the cytotoxic effects of ARA-C on both the LSCs and the leukemic progenitor cells. These data indicate that deferasirox is highly cytotoxic to AML cells; however, it is significantly more specific to AML initiating cells. In addition, deferasirox exhibited significant inhibitory effect on the proliferation of both the CD34+CD38− and CD34+CD38+ KG1a cell fractions accompanying by an S-phase arrest. The inhibition of proliferation was also demonstrated using proliferation dye and colony assay on both the LIC-like cells and the LICs isolated from AML patient (p<0.001). Since deferasirox is an NFkB inhibitor which regulates HIF1α levels, and since HIF1α is selectively activated in AML stem cells and is essential for maintenance of these cells, we studied the effect of deferasirox on this pathway. We found that NFkB translocation to the nucleus was reduced by over 80% and as a result the binding of NFkB to the HIF1α promoter was decreased in the LIC-like cells treated with deferasirox. HIF1α was downregulated transcriptionally (~45% reduction) and translationally (~55% reduction) in the LIC-like cells while it was upregulated in the CD34+CD38+KG1a cells following deferasirox treatment. In order to understand which of deferasirox's properties is crucial for its apoptotic effect, we used the iron chelator, deferipron, which does not effect on NFkB or HIF1α and siHIF1α. Each one of these treatments alone did not lead to an apoptotic effect in LIC-like cells or in the CD34+CD38+ kg1a cells. Conversely, the combination of the two lead to an increase in apoptosis in the LIC-like cells suggesting that only a combination of iron chelation and HIF1α reduction is sufficient to result in an apoptotic response. The apoptotic effect wasn't observed in the CD34+CD38+ fraction. These data hint that AML-LICs are selectively targeted by deferasirox. We describe a novel and unique anti-LIC property of deferasirox, which was originally developed as an iron chelator. We found clinically relevant concentrations of deferasirox to be cytotoxic in vitro to AML progenitor cells but even more potent against LICs. We believe that deferasirox exerts its cytotoxic effect, at least in part, by downregulating HIF1α levels in the LIC population. Pending further characterization, deferasirox can be considered as a potential therapeutic agent for eradicating LICs. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document