- Exploiting the unique phenotypes of the earthworm Eudrilus eugeniae to evaluate the toxicity of chemical substances. [Journal Article]
- EMEnviron Monit Assess 2018 Feb 16; 190(3):145
- Both the evaluation and the determination of toxicity of chemical substances present in the environment have implications in human health. In this present study, the natural phenomenon named autotomy...
Both the evaluation and the determination of toxicity of chemical substances present in the environment have implications in human health. In this present study, the natural phenomenon named autotomy, a self-defense mechanism employed by several animals against the toxic chemical contaminants, was considered to assess the toxicity of different chemical substances. We investigated the effects of glucose, sodium chloride, kanamycin, mercuric chloride, arsenic trioxide, and lead oxide on the phenotypes of earthworm Eudrilus eugeniae. Depending on the concentration of different chemicals, worms exhibit unique phenotypes. These phenotypes can be used to identify the toxicity as well as the toxic concentration of the chemicals. Upon exposure to toxic chemicals, worms use different mechanical forces at the site of cleavage furrow to detach its segments. During the detachment, there is no apparent blood loss at both the ends of the worm. Our results show that the mercuric chloride is toxic at the concentration above 5 μg when compared to other chemicals. Based on our findings, the toxic effects of a chemical and the toxic concentration of a chemical can be evaluated in both cost and time-efficient manner; in addition, these chemicals can be classified into the following categories: (1) mercuric chloride is extreme-toxic, (2) arsenic trioxide and lead oxide is toxic, (3) kanamycin and sodium chloride is low-toxic, and (4) glucose is non-toxic.
- Transcriptomic analysis of the PI3K/Akt signaling pathway reveals the dual role of the c-Jun oncogene in cytotoxicity and the development of resistance in HL-60 leukemia cells in response to arsenic trioxide. [Journal Article]
- ACAdv Clin Exp Med 2017; 26(9):1335-1342
- CONCLUSIONS: The overall results indicate that CCND1, FOXO1, and JUN may contribute to the induction of resistance to ATO, and that the C-Jun N-terminal kinase (JNK) signaling pathway may have greater significance than the phosphoinositide 3-kinase (PI3K)/Akt pathway in mediating the cytotoxic effects of ATO and the development of resistance to ATO in the HL-60 cell line.
- Chloroquine exerts antitumor effects on NB4 acute promyelocytic leukemia cells and functions synergistically with arsenic trioxide. [Journal Article]
- OLOncol Lett 2018; 15(2):2024-2030
- Chloroquine (CQ) has been confirmed to exhibit antitumor effects on different types of cancer cell, but whether it exerts the same effect on acute promyelocytic leukemia (APL) cells remains to be con...
Chloroquine (CQ) has been confirmed to exhibit antitumor effects on different types of cancer cell, but whether it exerts the same effect on acute promyelocytic leukemia (APL) cells remains to be confirmed. In the present study, the effects of various concentrations of CQ on the growth, apoptosis and cell cycle distribution of NB4 cells, as well as the potential mechanisms underlying these effects, were examined. The combined effect of CQ and arsenic trioxide (ATO) on the growth of NB4 cells was also determined. The results of the present study demonstrated that CQ treatment inhibited cell proliferation, and induced mitochondrial pathway apoptosis and S phase arrest in a dose-dependent manner by regulating apoptosis- and cell cycle-related proteins. CQ and ATO had a synergistic effect on the growth inhibition of NB4 cells, which may have been induced through the inhibition of autophagy. In conclusion, the results of the present study indicated that CQ exhibits a cytotoxic effect on NB4 cells and has a synergistic effect when combined with ATO, which thereby improves the curative effect of ATO on APL.
- Oxidative phosphorylation as an emerging target in cancer therapy. [Journal Article]
- CCClin Cancer Res 2018 Feb 02
- Cancer cells have upregulated glycolysis compared to normal cells, which has led many to the assumption that oxidative phosphorylation (OXPHOS) is downregulated in all cancers. However, recent studi...
Cancer cells have upregulated glycolysis compared to normal cells, which has led many to the assumption that oxidative phosphorylation (OXPHOS) is downregulated in all cancers. However, recent studies have shown that OXPHOS can be also upregulated in certain cancers, including leukemias, lymphomas, pancreatic ductal adenocarcinoma, high OXPHOS subtype melanoma and endometrial carcinoma, and that this can occur even in the face of active glycolysis. OXPHOS inhibitors could therefore be used to target cancer subtypes in which OXPHOS is upregulated, and to alleviate therapeutically adverse tumor hypoxia. Several drugs including metformin, atovaquone and arsenic trioxide are used clinically for non-oncological indications, but emerging data demonstrates their potential use as OXPHOS inhibitors. We highlight novel applications of OXPHOS inhibitors with a suitable therapeutic index to target cancer cell metabolism.
- Arsenic trioxide attenuates STAT-3 activity and epithelial-mesenchymal transition through induction of SHP-1 in gastric cancer cells. [Journal Article]
- BCBMC Cancer 2018 02 06; 18(1):150
- CONCLUSIONS: Our data suggest that ATO inhibits STAT3 activity and EMT process by upregulation of SHP-1 in gastric cancer cells.
- [Acute Promyelocytic Leukemia - A Rare, Life-Threatening Disease with High Healing Chance]. [Journal Article]
- DMDtsch Med Wochenschr 2018; 143(3):152-156
- The acute promyelocytic leukemia (APL) is a rare disease. However, if diagnosed early and treated immediately high cure rates can be achieved. Signs of hematopoietic insufficiency such as cytopenias ...
The acute promyelocytic leukemia (APL) is a rare disease. However, if diagnosed early and treated immediately high cure rates can be achieved. Signs of hematopoietic insufficiency such as cytopenias or leucocytosis can be present at first presentation of the patients. Moreover, hemorrhagic diatheses due to coagulpathy are present in approximately 80 % of cases and contribute substatially to the high early death rate in APL patients, which has been reported as high as 30 % in population based studies. In case of initial suspicion of APL treatment with all-trans retinoic acid (ATRA) should be initated immediately to reduce the risk of fatal bleeding events and confirmation or exclusion of the PML-RARA transcript should not be awaited before start of ATRA treatment. While patients with a low or intermediate risk of relapse are treated with a combination of ATRA and arsenic trioxide (ATO), those with high risk of relapse still receive a combination regimen consisting of ATRA, anthracyclines and cytosine-arabinosid. However, treatment strategies are under clinical investigation aiming at reducing the administration of conventional chemotherapy in high risk APL patients. With the current treatment approaches cure rates of approximately 90 % of the patients with low or intermeditae risk APL can be achieved. Nevertheless, particularly the high initial death rate warrants further clinical and pathiobiologic studies to identify targets and means to decrease hemorrhagic complications in patients with APL.
- Comparison of induction therapy in non-high risk acute promyelocytic leukemia with arsenic trioxide or in combination with ATRA. [Journal Article]
- LRLeuk Res 2018 Jan 29; 66:85-88
- CONCLUSIONS: Although ATO has been considered a first-line therapy in patients with APL, several studies have reported improved outcomes with a combination of ATO plus ATRA. This study demonstrated a significant decrease in relapse with this combination compared with single ATO therapy and supported the importance of ATRA in APL treatment.
- Characteristics of doxorubicin-selected multidrug-resistant human leukemia HL-60 cells with tolerance to arsenic trioxide and contribution of leukemia stem cells. [Journal Article]
- OLOncol Lett 2018; 15(1):1255-1262
- The present study selected and characterized a multidrug-resistant HL-60 human acute promyelocytic leukemia cell line, HL-60/RS, by exposure to stepwise incremental doses of doxorubicin. The drug-res...
The present study selected and characterized a multidrug-resistant HL-60 human acute promyelocytic leukemia cell line, HL-60/RS, by exposure to stepwise incremental doses of doxorubicin. The drug-resistant HL-60/RS cells exhibited 85.68-fold resistance to doxorubicin and were cross-resistant to other chemotherapeutics, including cisplatin, daunorubicin, cytarabine, vincristine and etoposide. The cells over-expressed the transporters P-glycoprotein, multidrug-resistance-related protein 1 and breast-cancer-resistance protein, encoded by the adenosine triphosphate-binding cassette (ABC)B1, ABCC1 and ABCG2 genes, respectively. Unlike other recognized chemoresistant leukemia cell lines, HL-60/RS cells were also strongly cross-resistant to arsenic trioxide. The proportion of leukemia stem cells (LSCs) increased synchronously with increased of drug resistance in the doxorubicin-induced HL-60 cell population. The present study confirmed that doxorubicin-induced HL-60 cells exhibited multidrug-resistance and high arsenic-trioxide resistance. Drug-resistance in these cells may be due to surviving chemoresistant LSCs in the HL-60 population, which have been subjected to long and consecutive selection by doxorubicin.
- Arsenic trioxide: insights into its evolution to an anticancer agent. [Review]
- JBJ Biol Inorg Chem 2018 Feb 02
- Arsenic and its various forms have been in use in ancient Chinese medicine for more than 2000 years. Arsenicals have gained importance for having remedial effects for various diseases from syphilis t...
Arsenic and its various forms have been in use in ancient Chinese medicine for more than 2000 years. Arsenicals have gained importance for having remedial effects for various diseases from syphilis to cancer thus highlighting its role as a therapeutic agent even though it has been labelled as a potential 'poison'. The ability of arsenic, specifically arsenic trioxide, to treat acute promyelocytic leukaemia has radically changed the perception of this poison and has been the main factor for the re-emergence of this candidate to Western medicine for the treatment of leukaemia and other solid tumours. This review highlights the glorious history of arsenic and its various forms with major emphasis on arsenic trioxide as a therapeutic agent. The mechanism of action, pathogenesis, pharmacokinetic profile, safety concerns, ongoing clinical trials and various new forms of arsenic trioxide are discussed. The review also outlines the therapeutic ability of this drug, discusses the latest developments and recent investigations and potential advancement of arsenic trioxide as nanoformulations that has made it emerge as a potential remedial agent.
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- Antileukemic effects of neurokinin-1 receptor inhibition on hematologic malignant cells: a novel therapeutic potential for aprepitant. [Journal Article]
- ADAnticancer Drugs 2018; 29(3):243-252
- Genetic and laboratory studies have remodeled the conventional understanding of cancer pathogenesis by identifying different molecular alterations. Intrigued by the contribution of neurokinin-1 recep...
Genetic and laboratory studies have remodeled the conventional understanding of cancer pathogenesis by identifying different molecular alterations. Intrigued by the contribution of neurokinin-1 receptor (NK1R) network in cancer pathogenesis, we investigated the antileukemic effects of aprepitant, a nonpeptide antagonist of NK1R, in a panel of hematological cell lines. In this study, we found that aprepitant decreased the survival of all the tested cells; however, as compared with NB4, viability of the other cell lines was inhibited at higher concentrations. By increasing both p21 and p73 along with suppressing c-Myc and hTERT, aprepitant probably disordered cell distribution in the cell cycle, decreased DNA replication rate, and, thereby, impeded the proliferative capability of NB4 cells. Moreover, exposing cells to this agent led to activation of the caspase-3-dependent apoptotic pathway through altering the expression of apoptosis-related genes. Noteworthy, aprepitant also sensitized NB4 cells to the cytotoxic effects of arsenic trioxide and vincristine. Overall, it seems that pharmaceutical targeting of NK1R using aprepitant, either as a single agent or in combination, possesses novel promising potential for leukemia treatment strategies.