&lt;p&gt;6,7-Dihydroxy-2-(4′-hydroxyphenyl)naphthalene induces HCT116 cell apoptosis through activation of endoplasmic reticulum stress and the extrinsic apoptotic pathway&lt;/p&gt;

Chiu, Ching-Feng; Lai, Guan Ying; Ch, Chen; Chiu, Chien Chao; Hung, Shao Wen; Chang, Chi Fen

doi:10.2147/dddt.s193914

Cited by 8 publications

(10 citation statements)

References 45 publications

(45 reference statements)

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“…Overall, our results clearly depict the enhanced cytotoxic activity exerted by the FBX drug when encapsulated into the EMLs on the well-characterized human colorectal carcinoma (HCT 116) cells [ 26 , 27 , 28 , 29 ], making the base for the investigation of this optimized formula in vivo.…”

Section: Discussionmentioning

confidence: 77%

“…Based on the above evidence, we carried out in vitro cell experiments in which the encapsulation of FBX into EMLs was performed to enhance the toxic potential of the drug towards human colorectal carcinoma (HCT 116) cells, a well-known experimental model in cancer drug discovery to predict clinical efficacy of anti-cancer drugs [ 26 , 27 , 28 , 29 ]. As a first step, we determined the cytotoxic potential of the free drug (FBX-R) as well as of the optimized formula (FBX encapsulated into EMLs, FBX-EMLs) on HCT 116 cells, expressed as IC50, the concentration of the drug able to reduce the cell viability by 50%, an index frequently employed to compare the anti-proliferative activity and the toxic potential of different anti-cancer drugs [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, EMLs are more stable compared with other well-known vesicular carriers such as liposomes, showing low toxicity profile, prolonged drug release, and improved drug efficacy [ 24 , 25 ]. These characteristics of EMLs make the base for the investigation of this nanocarriers to formulate FBX, with the aim to improve the cytotoxicity of this drug on HCT 116 colorectal cancer cells, a well-established in vitro human cell line model used in drug screenings and drug discovery programs in the field of cancer to predict clinical response to anti-cancer drugs [ 26 , 27 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

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The Encapsulation of Febuxostat into Emulsomes Strongly Enhances the Cytotoxic Potential of the Drug on HCT 116 Colon Cancer Cells

et al. 2020

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Febuxostat (FBX) is a drug able to inhibit xanthine oxidase and reduce uric acid production commonly used for the treatment of hyperuricemia in subjects suffering from gout. Several studies have also been directed at its use as anti-cancer drug during the last years, opening a window for its off-label use. In the present study, an optimized formulation in terms of vesicle size and drug release, obtained by encapsulation of FBX into the emulsomes (FBX-EMLs), was evaluated for its cytotoxic potential in human colorectal carcinoma (HCT 116) cells. The optimized FBX-EMLs formula had an improved half maximal inhibitory concentration (IC50), about 4-fold lower, compared to the free drug. The cell cycle analysis showed a significant inhibition of the HCT 116 cells proliferation following FBX-EMLs treatment compared to all the other conditions, with a higher number of cells accumulating on G2/M and pre-G1 phases, paralleled by a significant reduction of cells in G0/G1 and S phases. The optimized formula was also able to significantly increase the percentage of cell population in both early and late stages of apoptosis, characterized by a higher intracellular caspase-3 concentration, as well as percentage of necrotic cells. Lastly, the FBX ability to decrease the mitochondrial membrane potential was enhanced when the drug was delivered into the EMLs. In conclusion, the new formulation of FBX into EMLs improved all the parameters related to the anti-proliferative activity and the toxic potential of the drug towards colorectal cancer cells.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Encapsulation of Febuxostat into Emulsomes Strongly Enhances the Cytotoxic Potential of the Drug on HCT 116 Colon Cancer Cells

et al. 2020

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“…One study using a pancreatic β-cell line (INS-1 cells) demonstrated that RLX behaves as both an estrogen receptor antagonist through nuclear estrogen response element-dependent actions and as an estrogen receptor agonist by suppressing triglyceride accumulation [ 30 ]. The endoplasmic reticulum (ER) regulates intracellular calcium concentrations and protein folding and trafficking [ 31 , 32 , 33 , 34 ]. ER stress, the disruption of these ER functions, is related to T2DM in humans [ 35 , 36 , 37 ].…”

Section: Introductionmentioning

confidence: 99%

Raloxifene Ameliorates Glucosamine-Induced Insulin Resistance in Ovariectomized Rats

Cheng

Chang

et al. 2021

Biomedicines

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Osteoarthritis (OA) and osteoporosis (OP) are common among older women, especially postmenopausal women. Glucosamine (GlcN) is a common medication for OA, but it may induce insulin resistance and β-cell dysfunction, especially if ovarian hormones are lacking. Raloxifene (RLX) is a selective estrogen receptor modulator and also an OP drug. Previously, we found that estrogen could improve GlcN-induced insulin resistance in ovariectomized (OVX) rats. Here, we further hypothesized that RLX, similarly to estrogen, can ameliorate GlcN-induced insulin resistance in OVX rats. We used GlcN to induce insulin resistance in OVX rats as a model for evaluating the protective effects of RLX in vivo. We used a pancreatic β-cell line, MIN-6, to study the mechanisms underlying the effect of RLX in GlcN-induced β-cell dysfunction in vitro. Increases in fasting plasma glucose, insulin, and homeostasis model assessments of insulin resistance in OVX Sprague Dawley rats treated with GlcN were reversed by RLX treatment (n = 8 in each group). Skeletal muscle GLUT-4 increased, liver PEPCK decreased, pancreatic islet hypertrophy, and β-cell apoptosis in OVX rats treated with GlcN was ameliorated by RLX. The negative effects of GlcN on insulin secretion and cell viability in MIN-6 cells were related to the upregulation of reticulum (ER) stress-associated proteins (C/EBP homologous protein, phospho-extracellular signal-regulated kinase, phospho-c-JunN-terminal kinase), the expression of which was reduced by RLX. Pretreatment with estrogen receptor antagonists reversed the protective effects of RLX. GlcN can induce insulin resistance, β-cell dysfunction, and apoptosis in OVX rats and increase ER stress-related proteins in β-cells, whereas RLX can reverse these adverse effects. The effects of RLX act mainly through estrogen receptor α; therefore, RLX may be a candidate drug for postmenopausal women with OA and OP.

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“…It has been reported that PERK/eIF2alpha/ATF4 activation during UPR increases tolerance to extreme hypoxia and promotes tumor growth under hypoxia condition 26,27 . In addition, PERK/eIF2alpha/ATF4 activation also can potentiate apoptosis in cancer cells 28,29 .…”

Section: Discussionmentioning

confidence: 99%

PUM1 knockdown prevents tumor progression by activating the PERK/eIF2/ATF4 signaling pathway in pancreatic adenocarcinoma cells

et al. 2019

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Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with very poor prognosis. Therefore, it is important to fully understand the molecular mechanism underlying its occurrence and development. Pumilio RNA-binding family member 1 (PUM1) has been reported to function as an oncogene in ovarian cancer and nonsmall cell lung cancer. However, its role and mechanism in PDAC have not been fully illuminated. Here, we found that the PUM1 protein levels were higher in PDAC tissues than in adjacent tissues and that PUM1 levels were significantly associated with TNM stage and overall survival time, indicating a correlation between high PUM1 expression and poor prognosis in patients with PDAC. In vitro and in vivo assays showed that PUM1 knockdown inhibited cell proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT), and promoted apoptosis in MIA PaCa-2 and PANC-1 cells. Through cDNA microarrays and ingenuity pathway analysis, we found that the activation of the eIF2 signaling pathway significantly correlated with PUM1 knockdown. These results were further confirmed by the increased levels of key components of the eIF2 signaling pathway, p-PERK, p-EIF2A, and ATF4 in PUM1 knockdown cells. We also found that PUM1 levels have a significant negative correlation with p-PERK levels in PDAC tissues and that PERK overexpression inhibited cell proliferation, migration, invasion, and EMT, and promoted apoptosis in vitro. Moreover, a PERK inhibitor alleviated the effects of PUM1 knockdown on cell proliferation, apoptosis, migration, invasion, and EMT. Taken together, our results revealed that PUM1 knockdown suppressed cell growth, invasion, and metastasis, and promoted apoptosis by activating the PERK/eIF2/ATF4 signaling pathway in PDAC cells. PUM1 could be a potential target to develop pharmaceuticals and novel therapeutic strategies for the treatment of PDAC.

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<p>6,7-Dihydroxy-2-(4′-hydroxyphenyl)naphthalene induces HCT116 cell apoptosis through activation of endoplasmic reticulum stress and the extrinsic apoptotic pathway</p>

Cited by 8 publications

References 45 publications

The Encapsulation of Febuxostat into Emulsomes Strongly Enhances the Cytotoxic Potential of the Drug on HCT 116 Colon Cancer Cells

The Encapsulation of Febuxostat into Emulsomes Strongly Enhances the Cytotoxic Potential of the Drug on HCT 116 Colon Cancer Cells

Raloxifene Ameliorates Glucosamine-Induced Insulin Resistance in Ovariectomized Rats

PUM1 knockdown prevents tumor progression by activating the PERK/eIF2/ATF4 signaling pathway in pancreatic adenocarcinoma cells

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