Targeted induction of apoptosis for cancer therapy: current progress and prospects

Bremer, Edwin; Dam, Go van; Kroesen, Bart-Jan; Leij, Lou de; Helfrich, Wijnand

doi:10.1016/j.molmed.2006.06.002

Cited by 116 publications

(97 citation statements)

References 73 publications

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“…Selective induction of tumor-cell apoptosis may become the basic strategy in the treatment of malignant tumors. Most of the available chemotherapy drugs work through destroying tumor cells by inducing apoptosis [23] . In our study, the MTT assay showed troglitazone inhibited growth of liver cancer cells in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Troglitazone, a peroxisome proliferator-activated receptor γ ligand, induces growth inhibition and apoptosis of HepG2 human liver cancer cells

Zhou¹,

Wen²,

Kang³

et al. 2008

WJG

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AIM:To examine the effect of troglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) ligand, on the proliferation and apoptosis of human liver cancer cells. METHODS:Liver cancer cell line HepG2 was cultured and treated with troglitazone. Cell proliferation was detected by 3-(4-,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay; apoptosis was detected by flow cytometry and terminal deoxynucleotidyl transferasemediated nick end labeling of DNA fragmentation sites (TUNEL) assay; and apoptosis-related protein was detected by immunocytochemistry and Western blotting. RESULTS:Troglitazone inhibited growth and induced apoptosis of HepG2 cells in a dose-dependent manner, and induced activation of caspase-3 expression. Troglitazone not only drove apoptosis-inhibiting factor survivin to translocate incompletely from the nucleus to the cytoplasm, but also inhibited expression of survivin, while it did not affect expression of apoptosis-promoting factor Bax. express PPARγ, and there is evidence that PPARγ ligands have anti-tumor activity [10][11][12][13][14][15][16][17][18][19][20] . One of the important effects of these drugs is induction of apoptosis, although the exact mechanism remains elusive. The present study used liver cancer cell line HepG2 that endogenously expresses PPARγ as an experimental model [15] to study the effects of PPARγ ligand troglitazone on proliferation and apoptosis of liver cancer cells. It also analyzed the molecular mechanisms of these effects in an attempt to provide experimental clues for the use of PPARγ ligands in the treatment of liver cancer. CONCLUSION: MATERIALS AND METHODS ChemicalsTroglitazone (Cayman Chemical Industry, USA) was dissolved in DMSO and then diluted to appropriate concentrations with culture medium. The final concentration of DMSO in the culture medium did not exceed 1 mL/L. Cell cultureHepG2 cells were cultured in Dulbecco's modified Eagle's medium (GIBCO Laboratories, Grand Island, NY, USA) containing 10% fetal bovine serum (FBS, GIBCO Laboratories), 100 U/mL penicillin, and 100 g/mL streptomycin. Cells were grown at 37℃ in an atmosphere of 95% air and 5% CO2. MTT assayCell proliferation was detected by 3-(4-,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) (Sigma, St Louis, MO, USA) assay. When cells were cultured to the log phase, they were seeded on a 96-well plate (2 × 10 4 cells/100 μL/well) for 24 h until confluence. Cells were divided into a control (DMSO) group and a troglitazone group. The concentration of troglitazone was 5, 10, 20, 40, 80 and 100 μmol/L. After 120 h, 10 μL MTT (5 g/L) was added and incubated at 37℃ for 4 h. DMSO (75 μL) was added to each well, which was oscillated for 10 min until the crystals were dissolved completely. Absorbance (A) was detected with an enzyme calibrator at 560 nm. Cell viability = (A of study group/A of control group) × 100%. The experiment was repeated twice. There were six wells for each concentration. Flow cytometryCells were seeded onto a six-well plate and allowe...

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Section: Discussionmentioning

confidence: 99%

Troglitazone, a peroxisome proliferator-activated receptor γ ligand, induces growth inhibition and apoptosis of HepG2 human liver cancer cells

Zhou¹,

Wen²,

Kang³

et al. 2008

WJG

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“…In the denominators, (D x ) 1 represents D 1 "alone" that inhibits a system x%, and (D x ) 2 is for D 2 "alone" that inhibits a system x%. In the numerators, (D) 1 and (D) 2 "in combination" also inhibit x%.…”

Section: Methodsmentioning

confidence: 99%

“…The survival and proliferation of cancer cells often depends on key oncogenic signaling intermediates, which provides an opportunity to inhibit such targets for the selective killing of cancer cells (1). However, the suppression of single cellular targets is unlikely to significantly extend disease-free survival for many cancer patients, as the amplification of redundant signaling pathways may allow for a negation of the inhibitory effect (2,3). This observation has prompted the development of combinatorial targeting strategies involving multiple oncogenic pathways to achieve more desirable outcomes (3).…”

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confidence: 99%

Identification of a Dual Inhibitor of Janus Kinase 2 (JAK2) and p70 Ribosomal S6 Kinase1 (S6K1) Pathways

Byun

Lim

Mun

et al. 2015

Journal of Biological Chemistry

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Background: An underlying cause of cancer therapeutic resistance is the hyperactivation of endogenous overlapping or redundant signaling pathways in cancer cells. Results: Gingerenone A selectively kills cancer cells through dual inhibition of JAK2 and S6K1. Conclusion: Co-targeting JAK2 and S6K1 induces synergistic anti-cancer effects. Significance: Investigating the targets of bioactive compounds can lead to suggestions for novel therapeutic strategies.

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“…While necrotic cell death results in cell lysis, cellular apoptosis is characterized morphologically by cell shrinkage, nuclear pyknosis, chromatin condensation, and blebbing of the plasma membrane. It seems that all known anticancer drugs kill cancer cells predominantly through apoptosis [26,27].…”

Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin induces apoptosis in skin cancer cell line A-431 via ROS pathway

Aghaei¹

2012

iosrphr

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Abstract--Dihydroartemisinin (DHA) is a derivative of artemisinin that has been shown to inhibit cell growth and induce apoptosis in the several cancer cells via reactive oxygen species (ROS) formation. The present study was designed to understand the mechanism underlying Dihydroartemisinin-induced apoptosis in the A-431 human skin cancer cell line.MTT viability assay was used to study the cell proliferation effect of Dihydroartemisinin. Annexin V-FITC and reactive oxygen species (ROS) formation were assessed to detect apoptosis. Dihydroartemisinin significantly inhibited cell proliferation in a concentration-dependent manner in A-431 cell line. Dihydroartemisinin significantly induced apoptosis, which was determined by Annexin V-FITC staining. Moreover, increase of ROS formation was observed in response to Dihydroartemisinin treatment. The results of this study suggest that Dihydroartemisinin inhibited cell proletarian and induced apoptosis in skin cancer cells via ROS pathways. These data might suggest that Dihydroartemisinin could be used as an agent for the treatment of skin cancer.

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Targeted induction of apoptosis for cancer therapy: current progress and prospects

Cited by 116 publications

References 73 publications

Troglitazone, a peroxisome proliferator-activated receptor γ ligand, induces growth inhibition and apoptosis of HepG2 human liver cancer cells

Troglitazone, a peroxisome proliferator-activated receptor γ ligand, induces growth inhibition and apoptosis of HepG2 human liver cancer cells

Identification of a Dual Inhibitor of Janus Kinase 2 (JAK2) and p70 Ribosomal S6 Kinase1 (S6K1) Pathways

Dihydroartemisinin induces apoptosis in skin cancer cell line A-431 via ROS pathway

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