1,724,074 research outputs found
HO-3867 Induces Apoptosis via the JNK Signaling Pathway in Human Osteosarcoma Cells
No full textMetastatic osteosarcoma often results in poor prognosis despite the application of surgical en bloc excision along with chemotherapy. HO-3867 is a curcumin analog that induces cell apoptosis in several cancers, but the apoptotic effect and its mechanisms on osteosarcoma cells are still unknown. After observing the decrease in cellular viability of three human osteosarcoma U2OS, HOS, and MG-63 cell lines, and the induction of cellular apoptosis and arrest in sub-G1 phase in U2OS and HOS cells by HO-3867, the human apoptosis array showed that heme oxygenase (HO)-1 and cleaved caspase-3 expressions had significant increases after HO-3867 treatment in U2OS cells and vice versa for cellular inhibitors of apoptosis (cIAP)1 and X-chromosome-linked IAP (XIAP). Western blot analysis verified the results and showed that HO-3867 activated the initiators of both extrinsic caspase 8 and intrinsic caspase 9, and significantly increased cleaved PARP expression in U2OS and HOS cells. Moreover, with the addition of HO-3867, ERK1/2, and JNK1/2 phosphorylation were increased in U2OS and HOS cells. Using the inhibitor of JNK (JNK in 8), HO-3867’s increases in cleaved caspases 3, 8, and 9 could be expectedly suppressed, indicating that JNK signaling is responsible for both apoptotic pathways, including extrinsic and intrinsic, in U2OS and HOS cells caused by HO-3867. Through JNK signaling, HO-3867 has proven to be effective in causing both extrinsic and intrinsic apoptotic pathways of human osteosarcoma cells
HO-3867 Induces ROS-Dependent Stress Response and Apoptotic Cell Death in Leishmania donovani
No full textLack of vaccine and increasing chemotherapeutic toxicities currently necessitate the development of effective and safe drugs against various forms of leishmaniases. We characterized the cellular stress induced by a novel curcumin analogue, HO-3867, encapsulated within the phosphatidylcholine-stearylamine (PC-SA) liposome for the first time against Leishmania. The liposomal formulation of HO-3867 (i.e., PC-SA/HO-3867) initiated oxidative stress-induced apoptosis in L. donovani, revealed by altered cell morphology, phosphatidylserine externalization, mitochondrial depolarization, intracellular lipid accumulation, and cell cycle arrest in promastigotes. Liposomal HO-3867 was observed to be a strong apoptosis inducer in L. donovani and L. major in a dose-dependent manner, yet completely safe for normal murine macrophages. Moreover, PC-SA/HO-3867 treatment induced L. donovani metacaspase and PARP1 activation along with downregulation of the Sir2 gene. PC-SA/HO-3867 arrested intracellular L. donovani amastigote burden in vitro, with reactive oxygen species (ROS) and nitric oxide (NO)-mediated parasite killing. These data suggest that liposomal HO-3867 represents a highly promising and non-toxic nanoparticle-based therapeutic platform against leishmaniasis inspiring further preclinical developments
DataSheet_1_HO-3867 Induces ROS-Dependent Stress Response and Apoptotic Cell Death in Leishmania donovani.doc
No full textLack of vaccine and increasing chemotherapeutic toxicities currently necessitate the development of effective and safe drugs against various forms of leishmaniases. We characterized the cellular stress induced by a novel curcumin analogue, HO-3867, encapsulated within the phosphatidylcholine-stearylamine (PC-SA) liposome for the first time against Leishmania. The liposomal formulation of HO-3867 (i.e., PC-SA/HO-3867) initiated oxidative stress-induced apoptosis in L. donovani, revealed by altered cell morphology, phosphatidylserine externalization, mitochondrial depolarization, intracellular lipid accumulation, and cell cycle arrest in promastigotes. Liposomal HO-3867 was observed to be a strong apoptosis inducer in L. donovani and L. major in a dose-dependent manner, yet completely safe for normal murine macrophages. Moreover, PC-SA/HO-3867 treatment induced L. donovani metacaspase and PARP1 activation along with downregulation of the Sir2 gene. PC-SA/HO-3867 arrested intracellular L. donovani amastigote burden in vitro, with reactive oxygen species (ROS) and nitric oxide (NO)-mediated parasite killing. These data suggest that liposomal HO-3867 represents a highly promising and non-toxic nanoparticle-based therapeutic platform against leishmaniasis inspiring further preclinical developments.</p
Anticancer Efficacy of a Difluorodiarylidenyl Piperidone (HO-3867) in Human Ovarian Cancer Cells and Tumor Xenografts
No full textThe purpose of this study was to evaluate the anticancer potency and mechanism of a novel difluorodiarylidenyl
piperidone (H-4073) and its N-hydroxypyrroline modification (HO-3867) in human ovarian cancer.
Studies were done using established human ovarian cancer cell lines (A2870, A2780cDDP, OV-4, SKOV3,
PA-1, and OVCAR3) as well as in a murine xenograft tumor (A2780) model. Both compounds were comparably
and significantly cytotoxic to A2780 cells. However, HO-3867 showed a preferential toxicity toward
ovarian cancer cells while sparing healthy cells. HO-3867 induced G2-M cell cycle arrest in A2780 cells
by modulating cell cycle regulatory molecules p53, p21, p27, cyclin-dependent kinase 2, and cyclin, and
promoted apoptosis by caspase-8 and caspase-3 activation. It also caused an increase in the expression of
functional Fas/CD95 and decreases in signal transducers and activators of transcription 3 (STAT3; Tyr705)
and JAK1 phosphorylation. There was a significant reduction in STAT3 downstream target protein levels including
Bcl-xL, Bcl-2, survivin, and vascular endothelial growth factor, suggesting that HO-3867 exposure
disrupted the JAK/STAT3 signaling pathway. In addition, HO-3867 significantly inhibited the growth of
the ovarian xenografted tumors in a dosage-dependent manner without any apparent toxicity. Western blot
analysis of the xenograft tumor tissues showed that HO-3867 inhibited pSTAT3 (Tyr705 and Ser727) and JAK1
and increased apoptotic markers cleaved caspase-3 and poly ADP ribose polymerase. HO-3867 exhibited
significant cytotoxicity toward ovarian cancer cells by inhibition of the JAK/STAT3 signaling pathway.
The study suggested that HO-3867 may be useful as a safe and effective anticancer agent for ovarian cancer
therapy
Cellular uptake, retention and bioabsorption of HO-3867, a fluorinated curcumin analog with potential antitumor properties
No full textCurcumin, a naturally-occurring compound found in the rhizome of Curcuma longa plant, is known for its antitumor
activities. However, its clinical efficacy is limited due to poor bioabsorption. A new class of synthetic analogs of curcumin,
namely diarylidenylpiperidone (DAP ), has been developed with substantially higher anticancer activity than curcumin.
However, its cellular uptake and bioabsorption have not been evaluated. In this study we have determined the absorption
of a representative DAP compound, HO-3867, using optical and electron paramagnetic resonance spectrometry. The
cellular uptake of HO-3867 was measured in a variety of cancer cell lines. HO-3867 was taken in cells within 15 minutes
of exposure and its uptake was more than 100-fold higher than curcumin. HO-3867 was also retained in cells in an active
form for 72 hours and possibly longer. HO-3867 was substantially cytotoxic to all the cancer cells tested. However, there
was no direct correlation between cellular uptake and cytotoxicity suggesting that the cytotoxic mechanisms could be cell-type specific. When administered to rats by intraperitoneal injection, significantly high levels of HO-3867 were found in the liver, kidney, stomach and blood after 3 hours. Also, significant accumulation of HO-3867 was found in murine tumor xenografts with a dose-dependent inhibition of tumor growth. The results suggest that the curcumin analog has substantially higher bioabsorption when compared to curcumin
The interactional origins of foreigner talk : municipal employees and foreign workers
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3867.pdf (Publisher’s version ) (Open Access
HO-3867, a STAT3 inhibitor induces apoptosis by inactivation of STAT3 activity in BRCA1-mutated ovarian cancer cells
No full textBRCA1 plays an important role in DNA damage and repair, homologous recombination, cell-cycle regulation and apoptosis. BRCA-mutated ovarian cancer often presents at an advanced stage, however, tend to have better response to platinum-based chemotherapy as compared with sporadic cases of epithelial ovarian cancer (EOC). In spite of this, most patients will develop a recurrence and eventually succumb to the disease. Preclinical studies are currently investigating natural compounds and their analogs for tumor-directed targets in ovarian cancer. The aim of this study is to investigate whether the STAT3 inhibitor HO-3867, a novel curcumin analog, has a therapeutic effect on BRCA1-mutated ovarian cancer. Our novel agent, HO-3867 and a commercial STAT3 inhibitor, STATTIC, significantly inhibited BRCA-mutated ovarian cancer cells in vitro in a dose- and time-dependent manner. BRCA-mutated ovarian cancer cells treated with HO-3867 exhibited a significant degree of apoptosis with elevated levels of cleaved caspase-3, caspase-7 and PARP. HO-3867 treatment induced more reactive oxygen species (ROS) in BRCA-mutated cells compared with wild-type cells, however, there was no increased ROS when benign ovarian surface epithelial cells were treated with HO-3867. BRCA1-mutated cancer cells had higher expression of Tyrosine-phosphorylated STAT3 (pTyr705) as compared with other STAT proteins. Furthermore, treatment of these cells with HO-3867 resulted in decreased expression of pTyr705 and its downstream targets cyclin D1, Bcl-2 and survivin. In addition, overexpression of STAT3 cDNA provided resistance to HO-3867-induced apoptosis. Our results show that HO-3867, a potent STAT3 inhibitor, may have a role as a biologically targeted agent for BRCA1-mutated cancers either as an adjunct to cytotoxic chemotherapy or as a single agent
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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