IGF-I activates caspases 3/7, 8 and 9 but does not induce cell death in colorectal cancer cells

Yang, Shi Yu; Bolvin, Capucine; Sales, Kevin M.; Fuller, Barry; Seifalian, Alexander M.; Winslet, Marc C.

doi:10.1186/1471-2407-9-158

Cited by 11 publications

(11 citation statements)

References 28 publications

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“…11,12 The results show that a higher concentration of H 2 O 2 increases 2 C 12 (a, c) and L 6 E 9 (b, d) skeletal muscle cells were challenged by H 2 O 2 at concentrations of 0.25, 0.5, and 1 mM for 2 h. Cell viability was determined with CellTiter-Blue reagent (Promega), cell survival (%) (a, b) was expressed as percentage of viable cell in treated groups to the untreated control group (0 mM). Dead cell was assessed with YOPRO-iodide (Invitrogen); cell death/survival ratio (c, d) was calculated according to the method mentioned in the text.…”

Section: Igf-i Reduced Muscle Cell Death After H 2 O 2 -Induced Oxidamentioning

confidence: 99%

“…10,11 Briefly, after treatment with IGF-I and oxidative stress, 20 ml of CellTiterBlue reagent (Promega) was added to each well without the removal of the medium. The plate was rocked on an orbital shaker gently for 2 min to help mixing of the CellTiter-Blue reagent with culture medium.…”

Section: Cell Viability Assaymentioning

confidence: 99%

“…11 Detection of DNA Fragmentation DNA fragmentation, the hallmark of apoptosis, was examined using DNA ladder detection kit (Millipore). Briefly, C 2 C 12 and L 6 E 9 cells were seeded in a 5-ml flask at a density of 2 Â 10 6 cells/flask with DMEM media containing 10% FBS and 1% PenStrep.…”

Section: Cell Death Assaymentioning

confidence: 99%

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Pretreatment with insulin-like growth factor I protects skeletal muscle cells against oxidative damage via PI3K/Akt and ERK1/2 MAPK pathways

Yang

Hoy

Fuller

et al. 2010

Laboratory Investigation

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Oxidative stress has an important role in the pathogenesis of many muscle diseases. The major contributors to oxidative stress in muscle tissue are reactive oxygen species such as oxygen ions, free radicals, and peroxides. Insulin-like growth factor I (IGF-I) has been shown to increase muscle mass and promote muscle cell proliferation, differentiation, and survival. We, therefore, hypothesized that IGF-I might also be cytoprotective for muscle cells during oxidative stress. Exogenous hydrogen peroxide (H 2 O 2 ) was used to induce oxidative stress/damage in two types of skeletal muscle cells. Apoptotic pathways were assessed after the oxidative damage and the effects of IGF-I on oxidative stress in muscle cells were examined. Different IGF-I sub-pathways were analyzed with measurement of the expression of pro-and antiapoptotic proteins. It was found that H 2 O 2 diminishes muscle cell viability and induces a caspase-independent apoptotic cell death. Pretreatment with IGF-I protects muscle cells from H 2 O 2 -induced cell death and enhances muscle cells survival. This effect appears to result from the promotion of the anti-apoptotic protein, Bcl2. Further investigation shows that protection is via an IGF-I sub-pathway: PI3K/Akt and ERK1/2 MAPK pathways. Protecting muscle cells from oxidative damage presents a potential application in the treatment of the muscle wasting, which appears in many muscle pathologies including Duchenne muscle dystrophy and sarcopenia. Many pathological muscle conditions, such as Duchenne muscle dystrophy (DMD) and sarcopenia, have been found to be associated with an increase in oxidative stress. 1 DMD is a severe progressive X-linked muscle disease with the absence of dystrophin, a protein providing structural integrity on the muscle cell membrane. Owing to the fragility of the DMD muscle membrane, normal muscular contraction in DMD destabilizes the myocyte membrane, causing intracellular accumulation of calcium. This stimulates oxidative metabolism, which generates free radicals and triggers the key pathological processes. 2 Sarcopenia is a condition with degenerative loss of skeletal muscle mass and strength associated with ageing. Mitochondrial (Mt) production of reactive oxygen species (ROS) has been shown to increase in skeletal muscle over the course of ageing, 3 which in turn reduces bioenergetic efficiency and leads to muscle fiber atrophy/loss. 4 Although DMD and sarcopenia have different pathological properties, they share a common syndrome, that is, muscle wasting. Abundant evidence implicates oxidative stress as a potential regulator of proteolytic pathways leading to muscle wasting. 5 Oxidative stress results from the activities of the reactive compounds called ROS. ROS are natural by-products in the normal metabolism of oxygen and have important roles in cell signalling. ROS including oxygen ions, free radicals, and peroxides usually have highly reactive properties because of the presence of unpaired valence shell electrons. During physiological homeostasis overall oxidati...

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Section: Igf-i Reduced Muscle Cell Death After H 2 O 2 -Induced Oxidamentioning

confidence: 99%

Section: Cell Viability Assaymentioning

confidence: 99%

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Pretreatment with insulin-like growth factor I protects skeletal muscle cells against oxidative damage via PI3K/Akt and ERK1/2 MAPK pathways

Yang

Hoy

Fuller

et al. 2010

Laboratory Investigation

Self Cite

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show abstract

“…cell viability was assessed using a previously reported method (10). for comparison, all cell viability data were presented as the percentage of treated cells to untreated cells, which was calculated using the following formula: cell viability (%) = ft/fc x 100; where Ft represents fluorescence reading for treated cells and Fc represent fluorescence reading for untreated cells in the cell viability assay.…”

Section: Determination Of the Level Of Anti-and Pro-apoptotic Proteinmentioning

confidence: 99%

“…cell death assessment was carried out with a previously described method (10,11). for comparison, the cell death index for treated and untreated cells was calculated with the formula: cell death index = ft/fc; where ft and fc represent the units of fluorescence (RLU) in the treated (Ft) and the untreated (fc) cells, respectively.…”

Section: Determination Of the Level Of Anti-and Pro-apoptotic Proteinmentioning

confidence: 99%

Inhibition of the p38 MAPK pathway sensitises human colon cancer cells to 5-fluorouracil treatment

Shi

2011

Int J Oncol

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Abstract. colorectal cancer is the third most common cause of cancer-related deaths in the Western world. 5-fluorouracil (5-fu) based chemotherapeutic regimes have been the mainstay of systemic treatment for disseminated colorectal cancer for many years. However, it only produces a 25% response rate due to the drug-resistance. the mitogen-activated protein kinase (MaPK) pathway is involved in the anti-apoptotic process; its activation provides cancer cells with a survival advantage to escape the apoptotic challenge. this study assessed whether the p38 MaPK pathway is involved in 5-fu resistance in colorectal cancer cells. 5-fu only or 5-fu combined with a p38 MaPK pathway inhibitor (SB203580) was used to treat 5-fu-resistant colorectal cancer cells. the effect of the treatment on cell viability, death and caspase activities was assessed. Western blotting was used to investigate the responses of apoptosis-related proteins following the treatment. results showed that p38 MaPK inhibitor significantly increased colorectal cancer cell sensitivity to 5-fu. SB203580 in combination with 5-FU significantly reduced cell viability (P<0.01), and increased cell death and cellular caspase activity (P<0.01). Western blotting data revealed that SB203580 sensitises cancer cells to 5-fu due to an increase in Bax expression. these findings suggest that p38 MAPK is involved in cancer cell survival, and that the inhibition of p38 MaPK can enhance 5-fu to kill colorectal cancer cells.

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The tankyrase‐specific inhibitor JW74 affects cell cycle progression and induces apoptosis and differentiation in osteosarcoma cell lines

et al. 2013

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Wnt/β-catenin is a major regulator of stem cell self-renewal and differentiation and this signaling pathway is aberrantly activated in a several cancers, including osteosarcoma (OS). Attenuation of Wnt/β-catenin activity by tankyrase inhibitors is an appealing strategy in treatment of OS. The efficacy of the tankyrase inhibitor JW74 was evaluated in three OS cell lines (KPD, U2OS, and SaOS-2) both at the molecular and functional level. At the molecular level, JW74 induces stabilization of AXIN2, a key component of the β-catenin destruction complex, resulting in reduced levels of nuclear β-catenin. At the functional level, JW74 induces reduced cell growth in all three tested cell lines, in part due to a delay in cell cycle progression and in part due to an induction of caspase-3-mediated apoptosis. Furthermore, JW74 induces differentiation in U2OS cells, which under standard conditions are resistant to osteogenic differentiation. JW74 also enhances differentiation of OS cell lines, which do not harbor a differentiation block. Interestingly, microRNAs (miRNAs) of the let-7 family, which are known tumor suppressors and inducers of differentiation, are significantly upregulated following treatment with JW74. We demonstrate for the first time that tankyrase inhibition triggers reduced cell growth and differentiation of OS cells. This may in part be due to an induction of let-7 miRNA. The presented data open for novel therapeutic strategies in the treatment of malignant OS.

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IGF-I activates caspases 3/7, 8 and 9 but does not induce cell death in colorectal cancer cells

Cited by 11 publications

References 28 publications

Pretreatment with insulin-like growth factor I protects skeletal muscle cells against oxidative damage via PI3K/Akt and ERK1/2 MAPK pathways

Pretreatment with insulin-like growth factor I protects skeletal muscle cells against oxidative damage via PI3K/Akt and ERK1/2 MAPK pathways

Inhibition of the p38 MAPK pathway sensitises human colon cancer cells to 5-fluorouracil treatment

The tankyrase‐specific inhibitor JW74 affects cell cycle progression and induces apoptosis and differentiation in osteosarcoma cell lines

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