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          6-Methylguanine-DNA-methyltransferase promoter demethylation is involved in basic fibroblast growth factor–induced resistance against temozolomide in human melanoma cells

Fontijn, Dennis; Adema, Auke D.; Bhakat, Kishor K.; Pinedo, H.M.; Peters, Godefridus J.; Boven, Epie

doi:10.1158/1535-7163.mct-07-0044

Cited by 11 publications

(7 citation statements)

References 33 publications

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“…6,7,9 Temozolomide, a DNA-alkylating agent, inhibits tumor growth by its ability to add methyl groups to the O 6 position of guanines. 3,[12][13][14]40,41 In addition, TMZ induces autophagy. 18 Thus, it has been proposed that the autophagic pathway plays a role in the cytotoxic effects of TMZ.…”

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confidence: 99%

Chloroquine enhances temozolomide cytotoxicity in malignant gliomas by blocking autophagy

Golden

Cho²,

Jahanian

et al. 2014

FOC

153

117

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Object In a recent clinical trial, patients with newly diagnosed glioblastoma multiforme benefited from chloroquine (CQ) in combination with conventional therapy (resection, temozolomide [TMZ], and radiation therapy). In the present study, the authors report the mechanism by which CQ enhances the therapeutic efficacy of TMZ to aid future studies aimed at improving this therapeutic regimen. Methods Using in vitro and in vivo experiments, the authors determined the mechanism by which CQ enhances TMZ cytotoxicity. They focused on the inhibition-of-autophagy mechanism of CQ by knockdown of the autophagy-associated proteins or treatment with autophagy inhibitors. This mechanism was tested using an in vivo model with subcutaneously implanted U87MG tumors from mice treated with CQ in combination with TMZ. Results Knockdown of the autophagy-associated proteins (GRP78 and Beclin) or treatment with the autophagy inhibitor, 3-methyl adenine (3-MA), blocked autophagosome formation and reduced CQ cytotoxicity, suggesting that autophagosome accumulation precedes CQ-induced cell death. In contrast, blocking autophagosome formation with knockdown of GRP78 or treatment with 3-MA enhanced TMZ cytotoxicity, suggesting that the autophagy pathway protects from TMZ-induced cytotoxicity. CQ in combination with TMZ significantly increased the amounts of LC3B-II (a marker for autophagosome levels), CHOP/GADD-153, and cleaved PARP (a marker for apoptosis) over those with untreated or individual drug-treated glioma cells. These molecular mechanisms seemed to take place in vivo as well. Subcutaneously implanted U87MG tumors from mice treated with CQ in combination with TMZ displayed higher levels of CHOP/GADD-153 than did untreated or individual drug-treated tumors. Conclusions Taken together, these results demonstrate that CQ blocks autophagy and triggers endoplasmic reticulum stress, thereby increasing the chemosensitivity of glioma cells to TMZ.

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confidence: 99%

Chloroquine enhances temozolomide cytotoxicity in malignant gliomas by blocking autophagy

Golden

Cho²,

Jahanian

et al. 2014

FOC

153

117

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“…9). In addition, growth factor-mediated signaling has been reported to induce resistance in tumor cells (10,11). Other studies have also shown that the transcription factor hypoxia-inducible factor-1α (HIF-1α) and its downstream gene products [e.g., MDR1 and vascular endothelial growth factor (VEGF)] were responsible for drug resistance (12,13) and angiogenesis under hypoxic conditions (14).…”

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confidence: 99%

An Akt/Hypoxia-Inducible Factor-1α/Platelet-Derived Growth Factor-BB Autocrine Loop Mediates Hypoxia-Induced Chemoresistance in Liver Cancer Cells and Tumorigenic Hepatic Progenitor Cells

Lau

Yang

et al. 2009

Clinical Cancer Research

106

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Purpose: The goals of the present study were to investigate the mechanism of hypoxiamediated chemoresistance in liver cancer cells and tumorigenic hepatic progenitor (oval) cells and to determine whether disrupting an Akt/hypoxia-inducible factor-1α (HIF-1α)/platelet-derived growth factor (PDGF)-BB autocrine loop can enhance chemotherapeutic efficacy in hypoxia. Experimental Design: Five hepatocellular carcinoma (HCC) cell lines and two hepatic progenitor cell lines were treated in vitro with cisplatin under both normoxic and hypoxic conditions. To generate ischemic hypoxia for tumor cells in vivo, hepatic artery ligation was applied to an orthotopic HCC model. Cisplatin and YC1, which is a HIF-1α inhibitor, were administered by portal vein and intratumoral injections, respectively. Results: Cell viability was higher under hypoxic than normoxic conditions. HIF-1α and Akt were up-regulated under hypoxic conditions, forming an autocrine signaling loop with PDGF-BB. Akt/HIF-1α/PDGF-BB signaling regulated Akt to confer cisplatin resistance to HCC cell lines in vitro. This autocrine signaling loop also contributed to chemoresistance in the tumorigenic hepatic progenitor cell line PIL2 under hypoxic conditions but not in the nontumorigenic cell line PIL4. In an orthotopic HCC model, combining blockade of HIF-1α activity with ischemic hypoxia significantly enhanced the efficacy of chemotherapy, leading to suppression of tumor growth and prolongation of animal survival. Conclusion: Blockade of Akt/HIF-1α/PDGF-BB autocrine signaling could enhance the chemosensitivity of liver cancer cells and tumorigenic hepatic progenitor cells under hypoxic conditions and thus provide an effective therapeutic strategy for HCC.

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“…For comparison of cytotoxicity and establishment of the leader compound the organotin complexes 3 , 4 , 6 , 7 based on 2,6‐di‐ tert ‐butyl‐4‐mercaptophenol were also tested against 8 types of human cancer cell lines. The activity was compared with literature data for cisplatin …”

Section: Resultsmentioning

confidence: 99%

Antioxidative vs cytotoxic activities of organotin complexes bearing 2,6‐di‐tert‐butylphenol moieties

Antonenko

Shpakovsky

Vorobyov

et al. 2018

Applied Organom Chemis

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Two series of organotin(IV) complexes with Sn–S bonds on the base of 2,6‐di‐tert‐butyl‐4‐mercaptophenol (L1SH) of formulae Me2Sn(L1S)2 (1); Et2Sn(L1S)2 (2); Bu2Sn(L1S)2 (3); Ph2Sn(L1S)2 (4); (L1)2Sn(L1S)2 (5); Me3Sn(L1S) (6); Ph3Sn(L1S) (7) (L1 = 3,5‐di‐tert‐butyl‐4‐hydroxyphenyl), together with the new ones [Me3SnCl(L2)] (8), [Me2SnCl2(L2)2] (9) (L2 = 2‐(N‐3′,5′‐di‐tert‐butyl‐4′‐hydroxyphenyl)‐iminomethylphenol) were used to study their antioxidant and cytotoxic activity. Novel complexes 8, 9 of MenSnCl4 − n (n = 3, 2) with Schiff base were synthesized and characterized by 1H, 13C NMR, IR and elemental analysis. The crystal structures of compounds 8 and 9 were determined by X‐ray diffraction analysis. The distorted tetrahedral geometry around the Sn center in the monocrystals of 8 was revealed, the Schiff base is coordinated to the tin(IV) atom by electrostatic interaction and formation of short contact Sn–O 2.805 Å. In the case of complex 9 the distorted octahedron coordination of Sn atom is formed. The antioxidant activity of compounds as radical scavengers and reducing agents was proved spectrophotometrically in tests with stable radical DPPH, reduction of Cu2+ (CUPRAC method) and interaction with superoxide radical‐anion. Moreover, compounds have been screened for in vitro cytotoxicity on eight human cancer cell lines. A high activity against all cell lines with IC50 values 60–160 nM was determined for the triphenyltin complex 7, while the introduction of Schiff base decreased the cytotoxicity of the complexes. The influence on mitochondrial potential and mitochondrial permeability for the compounds 8 and 9 has been studied. It is shown that studied complexes depolarize the mitochondria but don't influence the calcium‐induced mitochondrial permeability transition.

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O 6-Methylguanine-DNA-methyltransferase promoter demethylation is involved in basic fibroblast growth factor–induced resistance against temozolomide in human melanoma cells

Cited by 11 publications

References 33 publications

Chloroquine enhances temozolomide cytotoxicity in malignant gliomas by blocking autophagy

Chloroquine enhances temozolomide cytotoxicity in malignant gliomas by blocking autophagy

An Akt/Hypoxia-Inducible Factor-1α/Platelet-Derived Growth Factor-BB Autocrine Loop Mediates Hypoxia-Induced Chemoresistance in Liver Cancer Cells and Tumorigenic Hepatic Progenitor Cells

Antioxidative vs cytotoxic activities of organotin complexes bearing 2,6‐di‐tert‐butylphenol moieties

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