Niclosamide, an FDA approved salicyclamide derivative used for the treatment of tapeworm infections, targets the Wnt/β-catenin pathway. Annexin V-fluorescein isothiocyanate (FITC)/ propidium iodide (PI) apoptosis detection kit was purchased from BD (San Jose, CA, USA). Importantly, we demonstrated that cellular bioenergetics was dramatically repressed by Niclosamide addition. Giving abiraterone acetate, niclosamide, and prednisone may be a better treatment for patients with castration-resistant prostate cancer. Niclosamide suspension (20 mg/kg) was injected via intraperitoneal perfusion, once a day, for two consecutive weeks. We found that abolishment of the excess ROS production with NAC (10 mM) abrogated the Niclosamide-induced cell apoptosis under glucose deprivation (Figure 4D). Basal ECAR were measured at three time points, followed by sequential injections of the Glucose (10 mM), Oligomycin (1 μM), and 2-DG (100 mM). E. Changes in body weight in saline- or Niclosamide-treated mice. Molecular Cancer Therapeutics. Representative images of colonies and total colonies were recorded and calculated. Epithelial ovarian cancer (EOC) is the leading cause of gynecologic cancer mortality worldwide. thismailbody4 = thismailbody4 + "4;";
2014;5(4):1281-1294, 26. Ovarian carcinoma is a common malignant tumor of the female reproductive organs with an incidence rate second only to cervical and endometrial cancers [1]. Drugs with few side effects and high safety are clearly needed. Tumorspheres were treated, and Wnt transcriptional activity was measured by the TOPflash reporter assay. B. SKOV3 cells were treated with Niclosamide in the presence or absence of glucose for 12 hr, then subjected to culture for 3 days. Both SKOV3 and HO8910 cells were counted and a total of 800 cells per well were seeded evenly into 6-well plates and incubated at 37°C for 7-10 days in a humidified incubator with 5% CO2. A. 2011;71(12):4172-4182, 8. var thismailbody1 = "";
These results suggest that using niclosamide is an attractive strategy to suppress the growth of ovarian cancer cells with aberrant Wnt signaling activation. A functional mammalian target of rapamycin complex 1 signaling is indispensable for c-Myc-driven hepatocarcinogenesis. Bethesda, MD 20894, Copyright Gynecologic Oncology. Ovarian cancer treatment remains a challenge and targeting cancer stem cells presents a promising strategy. The Anti-Helminthic Niclosamide inhibits Wnt/Frizzled1 signaling. Antihelminth Compound Niclosamide downregulates Wnt signaling and elicits antitumor responses in tumors with activating APC mutations. Each assay was performed in triplicate and data was derived from at least three independent experiments. Cellular Signalling. Niclosamide suppresses cancer cell growth by inducing Wnt co-receptor LRP6 degradation and inhibiting the Wnt/β-catenin pathway. 1. Copyright © 2014 Elsevier Inc. All rights reserved. The chemical constitution of respiration ferment. thismailbody4 = thismailbody4 + "4;";
A. F. Western blot analyses of p-MSK1, p-MEK1/2, MEK1/2, p-ERK1/2, and ERK1/2 pathways in tumor tissues derived from saline- or Niclosamide-treated mice. Immunoreactive proteins were detected by ECL reagent according to the manufacturer's protocol (Biyetime bioteconology). The primary antibodies against HK2 (500994), PFKM (505477), PGK1 (501965), and LDHA (501146) were obtained from Zen Bioscience (Chengdu, China). JAK-STAT signaling also appears to be a potential target of Niclosamide in multiple myeloma and human lung cancer cells [12, 13]. Glucose metabolism, glutamine metabolism, and lipid metabolism are the most significant metabolic pathways that commonly reprograming in tumor cells. This causes the worms to detach from the intestinal wall and be excreted with the feces [5]. Walters Haygood CL, Arend RC, Gangrade A, Chettiar S, Regan N, Hassmann CJ 2nd, Li PK, Hidalgo B, Straughn JM Jr, Buchsbaum DJ. document.write(thismailbody4 + thismailbody3+thismailbody2)
Immunotherapeutic approaches are primarily aimed at the use of immunological checkpoint inhibitors, including PD-1/PD-L1 inhibitors and inhibitors of CTLA-4 [4]. We also found that the cell growth inhibition in Niclosamide-treated, glucose-deprived cells was also rescued by NAC (10 mM) administration (Figure 4E). Importantly, Niclosamide has been confirmed to target the Wnt/β-catenin, mTOR, STAT3, NF-κB, and Notch pathways has been widely investigated in multiple cancer types. E. SKOV3 cells were treated with Niclosamide and/or NAC in the presence or absence of glucose for 12 hr, and then cultured for 3 days. Li Y, Li P K, Roberts M J. et al. Multi-targeted therapy of cancer by Niclosamide: A new application for an old drug. Cells were then treated with different concentrations (0, 0.5, 1, 2, 4, 8, 16, or 32 μM) of Niclosamide or DMSO (vehicle control) for 48 hr, followed by Niclosamide incubating with CCK-8 for another 3 hr at 37°C. Assessment and management of diarrhea following VEGF receptor TKI treatment in patients with ovarian cancer. Mol Cell. 1. Recent Patents on Anti-Cancer Drug Discovery. Blots were blocked at room temperature for 1.5 hr in 5% non-fat milk in Tris-buffered saline (TBS)-Tween (TBS-T) on a shaker, and then incubated with the primary antibodies in 5% non-fat milk TBS-T overnight at 4°C. Western blot analysis showed a decrease in Wnt/β-catenin pathway proteins and the expression of target genes. Niclosamide In ovarian cancer, niclosamide significantly decreased the expression of proteins in the wingless/integrated (Wnt), mammalian target F.G.S., S.D.Y., G.W.Q., and Q.Z.C. Western blotting was used to detect expressed proteins. Alexiou A, Soursou G, Chatzichronis S. et al. Trypan blue was obtained from Life Technologies (Carlsbad, CA). B. Interestingly, Niclosamide triggered ROS-mediated JNK activation to promote cell apoptosis under glucose deprivation, suggesting that Niclosamide may be a promising compound for ovarian cancer therapy. These findings warrant further research of this drug and other niclosamide analogs as a treatment option for ovarian cancer. Although recent studies demonstrated that niclosamide could be a potential anticancer agent, its poor water solubility needs to be overcome before further preclinical and clinical investigations can be conducted. Breast carcinoma is the most common female cancer with considerable metastatic potential. Keywords: Niclosamide, ovarian carcinoma, cellular bioenergetics, MEK1/2-ERK1/2 signal. Niclosamide suppresses cancer cell growth by inducing Wnt Co-Receptor LRP6 degradation and inhibiting the Wnt/β-Catenin pathway. Arend RC, Londoño-Joshi AI, Straughn JM Jr, Buchsbaum DJ. F. Western blot analysis of p-JNK and JNK in Niclosamide treated SKOV3 cells with or without NAC and in the presence or absence of glucose for 12 hr. Liu J, Nicum S, Reichardt P. et al. Actin was used as a loading control. We speculated that Niclosamide treatment may interrupt mitochondrial homeostasis and then may up-regulate SLC1A5 to activate mTOR signaling. thismailbody12 = thismailbody12+thismailbody11;
Overall, mitochondrial respiration and aerobic glycolysis were both decreased by Niclosamide treatment. Tissue homogenates were cleared by centrifugation at 13,000 rpm for 25 min at 4°C, and the supernatants were collected in clean microcentrifuge tubes on ice.
The mitochondria also showed morphological fragmentation changes and were fewer in number following Niclosamide addition (Figure 2E). In the present studies, Niclosamide showed tumor-suppressive activity in SKOV3 and HO8910 ovarian cancer cells as confirmed by a dose-dependent decrease in cell viability (Figure 1A). A previous study showed that c-Myc up-regulates SLC1A5 to promote amino acid metabolism, which subsequently activates mTORC1 signaling to favor hepatocarcinogenesis [24, 25]. The Wnt/β-catenin pathway is known to regulate cellular proliferation and plays a role in chemoresistance. Epub 2013 Oct 11. 2011;1(10):e39, 14. Actin was used as a loading control. Even Cancer Cells Watch Their Cholesterol. Cancer Cell. Objective Niclosamide has shown activity against ovarian cancer in vitro; however, it has low bioavailability in vivo. Here, we reported our finding with niclosamide, an FDA approved anthelmintic drug. Warburg O. Cancer Research. We also found a slight increase in the basal glycolytic rate and expression of the glycolytic enzymes HK2 and PKM2, despite the overall decrease in glycolysis. Therefore, we evaluated a novel nanosuspension of niclosamide (nano-NI) for its effect against ovarian cancer. 2009;48(43):10267-10274, 7. Tel: +86-535-6913227 E-mail address: caoqizhi
However, the effective rate of a single drug is still only about 10%, so the efficacy of combined drugs needs further study. 2019;56(6):4530-4538, 23. Colonies were counted by two independent investigators. Result: Niclosamide treatment significantly suppressed ovarian carcinoma growth and induced cell apoptosis by inactivating MEK1/2-ERK1/2 mediated signal transduction. Cell apoptosis was measured by flow cytometry. Targeting metabolic reprograming can therefore significantly inhibit tumor growth and promote apoptosis. E. The mitochondrial morphology in Niclosamide treated SKOV3 and HO8910 cells were examined by DAPI and MitoTracker Red. 2018;1859(4):263-269, 24. To understand the cleavage of OPA1 in niclosamide treated cells, we further detected mitochondrial membrane potential (MMP) and found MMP was signidicantly decreased which indicated niclosamide caused mitochodnrial depolarization (Figure 2G). Chen M, Wang J, Lu J. et al. Science. Importantly, niclosamide was able to inhibit the tumor formation of ovarian-cancer-initiating cells derived from cancer cell lines in vivo and tumor growth of breast cancer stem-like cell subpopulations in vivo. International Journal of Gynecological Cancer. doi: 10.1371/journal.pone.0029290. Jin B, Wang C, Li J, Du X, Ding K, Pan J. Anthelmintic niclosamide disrupts the interplay of p65 and FOXM1/beta-catenin and eradicates leukemia stem cells in chronic myelogenous leukemia. Wang Q, Holst J. L-type amino acid transport and cancer: targeting the mTORC1 pathway to inhibit neoplasia. International Journal of Biological Sciences, International Journal of Medical Sciences, J Cancer
Molecular Cancer Therapeutics. Further work is needed to determine the detailed mechanism underlying this process. Niclosamide suppresses abnormal cellular processes by targeting RELA (NFKB) and STAT3 signaling in cancer cells [32– 35, 37, 38]. Representative images of sacrificed mice from physiological saline and Niclosamide treated groups. Cancer cell must meet new requirements for materials, energy, and redox forces to support their rapid proliferation, so tumor cells commonly show reprograming of metabolic pathways [20]. D. Changes in tumor weight in mice treated with saline or Niclosamide. Niclosamide, a drug used to deal with tapeworm infections, attacks cells with a p53 deficiency, a deficiency that the majority of cancer cells possess, causing apoptosis or cancer cell death and reducing tumour size by up to 50%; it can also attack restrict metastasis and cancer cell migration and inhibit cancer stem cells. A and B. Several studies have evaluated the anti-tumor activity of Niclosamide in suppressing prostate cancer, breast cancer, osteosarcoma, and colorectal carcinoma. Flow cytometry analysis of cell apoptosis after the ovarian carcinoma cells treated with Niclosamide in the presence or absence of glucose for 12 hr. These data confirmed that Niclosamide has promising tumor-suppressive activity in ovarian carcinoma cells. Actin was used as a loading control. JNK is known to play dual roles in multiple carcinogenesis by activating tumor-associated signal pathways and by initiating cell apoptosis. For OCR determinations, cells were incubated in base assay medium (according to manufacturer's instructions) supplemented with 2 mM glutamine, 10 mM glucose, and 1 mM pyruvate for 1 hr, prior to the measurements using the XF Cell Mito Stress Kit (Seahorse Bioscience). Background: Ovarian carcinoma is a common malignant tumor of the female reproductive organs with an incidence rate second only to cervical and endometrial cancers. Data are presented as mean ± SD. Data are presented as mean ± SD. Female athymic nude mice were purchased from Shanghai Laboratory Animal Center, CAS (Shanghai, China) and housed in a specific pathogen-free (SPF) environment. doi:10.7150/jca.41418, Fugen Shangguan1,2*, Yan Liu3*, Li Ma3, Guiwu Qu4, Qing Lv4, Jing An5, Shude Yang6, Bin Lu1 , Qizhi Cao3,4. The Seahorse bioenergetics analysis data confirmed that Niclosamide dramatically inhibited the overall mitochondrial oxygen consumption rate (OCR) (Figure 2A). 2015;3(11):1257-1268, 5. Niclosamide is an "old" antihelminthic drug that uncouples mitochondria of intestinal parasites. 2019;38(1):184. All authors read and approved the final manuscript. Therefore, we investigated the cytotoxicity of niclosamide analogs in combination with carboplatin against ovarian cancer patient ascites cells and tissue slices. A Seahorse XF96 analyzer was used to measure cellular bioenergetics. Therefore, we investigated the cytotoxicity of niclosamide analogs in combination with carboplatin against ovarian cancer patient ascites cells and tissue slices. Niclosamide examination of tumor growth associated pathways and MEK1/2-ERK1/2 signaling associated molecules revealed inactivation of MSK1, MEK1/2, and ERK1/2 as well as reduction of K-ras in Niclosamide-treated cells (Figure 1E). Calculation of the OCR indexes of basal respiration, ATP production, and maximal respiration revealed dramatic reductions in all these indexes in Niclosamide-treated cells (Figure 2B-D). The potency of niclosamide on breast cancer was assessed in vitro and in vivo. Cancer Letters. Our interpretation is that the increase in basal ECAR maybe a stress response arising from the inhibition of mitochondrial respiration. In recent years, Niclosamide has been widely investigated in cancer research and has shown effective inhibition of multiple cancer-associated signal pathways. 2015;25(8):1377-1385, 18. Oral niclosamide inhibited tumor growth and progression in an intraperitoneal xenograft mouse model representative of human ovarian cancer. Redeployment-based drug screening identifies the anti-helminthic Niclosamide as anti-myeloma therapy that also reduces free light chain production. Data are presented as mean ± SE (n = 6). Cancer stem cells; Chemoresistance; LRP6; Niclosamide; Ovarian cancer; Wnt/β-catenin. edu.cn. The data presented in right graphs represent the mean ± SD. thismailbody1 = thismailbody12+"u&"+"#x";
Emerging agents that target signaling pathways in cancer stem cells. Molecular Metabolism. 2020 Apr 24;102(5):1011-1019. doi: 10.1093/biolre/ioaa010. In acute myelogenous leukemia and primary human glioblastoma cells, Niclosamide suppresses TAK1→IKK→IκBα→NF-κB signal transduction cascades and the expression of cleaved activated Notch1 receptor [14, 15]. Moreover, the strongest tumor suppressive phenotype was rescued by NAC (Figure S4B). COVID-19 is an emerging, rapidly evolving situation. Mechanistically, we found that Solute Carrier Family 1, Member 5 (SLC1A5) was increased in Niclosamide-treated SKOV3 and HO8910 cells. E. Western blotting analyses of p-MSK1, p-MEK1/2, MEK1/2, p-ERK1/2, ERK1/2 and K-ras in SKOV3 and HO8910 cells 24 hr after treatment with Niclosamide. Cells were then treated with gradient concentrations (0, 4, and 8 μM) of Niclosamide for 1, 2, 3 and 4 days, and followed by incubating with Cell Counting Kit-8 (CCK-8) for 3 hr at 37°C, respectively. var thismailbody2 = "";
The autonomous Notch signal pathway is activated by baicalin and baicalein but is suppressed by Niclosamide in K562 cells. Result: Niclosamide treatment significantly suppressed ovarian carcinoma growth and induced cell apoptosis by inactivating MEK1/2drial -ERK1/2 mediated signal transduction. Consistent with the in vitro carcinoma cell data, Niclosamide significantly suppressed tumor growth in this nude mouse model (Figure 5A and B). and S.D.Y., wrote the paper. For in vivo tumorigenesis analysis, nude mice at the age of 5 weeks were injected subcutaneously in the left flanks with 5 x 106 of SKOV3 cells in 0.1 mL serum-free PBS. This work was supported by the National Natural Science Foundation of China (81672757), Project of Science and Technology of Yantai (2016ZH082). Data are presented as mean ± SD. Osada T, Chen M, Yang X Y. et al. At the same time, the control group was injected with the same volume of castor oil. Recently, Niclosamide was also shown to enhance the efficacy of PD-1/PD-L1 immune checkpoint blockade and the cytotoxicity of cisplatin in non-small cell lung cancer (NSCLC) cells [16]. 2011;6(12):e29290, 9. The anthelmintic niclosamide inhibits colorectal cancer cell lines via modulation of the canonical and noncanonical Wnt signaling pathway. Eight human OPA1 isoforms, long and short: What are they for?. Aerobic glycolysis alterations in response to nNiclosamide. Niclosamide inhibits ovarian cancer in vivo and in vitro through metabolic approach [ 42 ]. thismailbody4 = thismailbody4 + "";
D. Flow cytometry analysis of cell apoptosis after the ovarian carcinoma cells were treated with Niclosamide and/or NAC in the presence or absence of glucose for 12 hr. Combination treatment produced increased cytotoxicity compared to single agent treatment in 32/34 patient samples. D. Representative morphological changes of SKOV3 and HO8910 cells in response to different concentrations of Niclosamide. We also found marked activation of JNK, a crucial kinase belonging to MAPK family, in Niclosamide-treated cells under glucose deprivation, but not when cells were treated with Niclosamide alone or under glucose deprivation alone (Figure 4C). Biochemistry. The most common type of ovarian cancer is epithelial cancer, followed by malignant germ cell tumors. In ovarian cancer cell lines, niclosamide may impact the Wnt/beta-catenin, mTOR, and STAT3 pathways. 2012 Apr;31(4):178-84. doi: 10.5732/cjc.011.10290. var thismailbody11 = "";
OBJECTIVE: Niclosamide has shown activity against ovarian cancer in vitro; however, it has low bioavailability in vivo. Epub 2020 Mar 21. Further work is needed to elucidate the mechanism by which Niclosamide promotes OPA1 cleavage and mitochondrial fission. Data are presented as mean ± SD. 2016 Jun 1;203(1):193-205. doi: 10.1016/j.jss.2016.03.051. BCA protein assay kit and Pierce ECL western blotting substrate were obtained from Beyotime Biotechnology (Shanghai, China). The cells were incubated at 37°C in a humidified incubator with 5% CO2. Metabolic reprogramming is one of the important features of tumor cells. Data are presented as mean ± SE (n = 6). Platinum-based therapy is the standard first line treatment Niclosamide (amuricide or molluscicide) is an anthelmintic salicylamide derivative that inhibits mitochondrial oxidative phosphorylation in the cells of parasitic worms, thereby restricting ATP production. The invention relates to niclosamide and derivates thereof, which effectively inhibit transcription of the S100A4 gene, resulting in inhibition and/or reduction of S100A4-induced cell motility, invasiveness, metastasis and proliferation of human cancer cells. The poor prognosis of this disease is due to difficult in an early diagnosis because of the anatomical location of the ovaries deep in the pelvic cavity, the small size of the ovaries, and the lack of typical symptoms of this cancer.
Scienze Del Turismo Bicocca,
17 Novembre 1999,
Due Multe Autovelox Stesso Giorno,
Ninna Nanna Bumbi,
La Città Del Futuro Libro,
Lucio Dalla Spartiti Pianoforte Pdf,