P53 dependent and independent apoptosis induced by lidamycin in human colorectal cancer cells

Chen, Lihui; Jiang, Jianming; Chen, Cheng; Yang, A-Jing; He, Qing; Li, Dian-Dong; Wang, Zhen

doi:10.4161/cbt.6.6.4193

Cited by 23 publications

(17 citation statements)

References 41 publications

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“…3A), consistent with previous study. 5 Under our experimental conditions, low concentration of LDM (0.5 nmol/L) did not confer extensive growth inhibition by itself. In the following experiments, we chose 0.5 nmol/L LDM as an appropriate dose to detect the potentiation effects of various shRNAs.…”

Section: Resultsmentioning

confidence: 97%

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Knockdown of Chk1 sensitizes human colon carcinoma HCT116 cells in a p53-dependent manner to lidamycin through abrogation of a G2/M checkpoint and induction of apoptosis

Pan¹,

Ren²,

He³

et al. 2009

Cancer Biology & Therapy

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Recent advances in cell cycle regulation have led to a suggestion of therapeutically targeting cell cycle checkpoint pathways in cancer cells to increase the toxicity of DNA-damaging agents. In this study, we investigate whether knockdowns of checkpoint kinases Chk1 and Chk2 by RNA interfering potentiate the cytotoxicity and abrogate G 2 /M checkpoint induced by DNA-damaging agent lidamycin (LDM) in HCT116 cells with different p53 status. Our results showed that Chk1 knockdown enhanced the cytotoxicity of LDM through abrogating G 2 /M arrest and increasing apoptosis to a greater extent in HCT116 p53 -/-cells than in p53 wt cells. Abrogation of LDM-induced G 2 /M arrest by Chk1 knockdown was associated with reducing the inactivated phosphorylations of Cdc25C and Cdc2. LDM-induced γ-H2AX was increased in cells with Chk1 knockdown, indicating that DNA double-strand breaks (DSBs) were enhanced. Furthermore, knockdown of Chk1 also increased LDM-mediated apoptotic cell death in p53 knockout cells with activation of caspase-2 and caspase-3. On the contrary, knockdown of Chk2 had no impact on G 2 /M arrest or apoptosis induced by LDM. Moreover, dual knockdown of Chk1 and Chk2 failed to achieve better efficacy than Chk1 alone. Taken together, we suggest that Chk1 is a potential therapeutic target to sensitize human p53 deficient cancer cells to LDM.

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Section: Resultsmentioning

confidence: 97%

“…3,4 Consistently, previous study has indicated that LDM conferred much greater cytotoxicity to human colorectal cancer cells with wild type p53 than those with mutant p53. 5 Hence, inhibiting the remaining checkpoint pathways in p53 -/-cancer cells might increase the tumor-specific toxicity of LDM.…”

Section: Introductionmentioning

confidence: 99%

Knockdown of Chk1 sensitizes human colon carcinoma HCT116 cells in a p53-dependent manner to lidamycin through abrogation of a G2/M checkpoint and induction of apoptosis

Pan¹,

Ren²,

He³

et al. 2009

Cancer Biology & Therapy

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“…Then RLSCS method was used to detect molar concentration change of the diffusing GNP before and after the enzyme cleavage reaction and it shows significant anticancer activity because of its ability to damage DNA by radical-mediated hydrogen abstraction. Different concentration of LDM can induce normal cells into the different apoptosis cells, in which different concentration of caspase 3 was included [34]. So when the lysates from normal cells and LDM-induced apoptotic cells were incubated with the cleavage substrates of caspase 3 (GNP dimer), the concentration ratio of GNP in apoptotic cells lysate (C) and normal cells lysate (C control ) determined by RLSCS method can be used for discrimination of different LDM-induced apoptotic cells from normal cells.…”

Section: Assays Of Caspase 3 Activity and Drug-induced Cell Apoptosismentioning

confidence: 99%

A single particle method for direct determination of molar concentrations of gold nanoparticles, and its application to the determination of the activity of caspase 3 and drug-induced cell apoptosis

et al. 2016

Microchim Acta

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We report on a method for direct determination of the molar concentration of gold nanoparticles (GNP) in solution by using resonance light scattering correlation spectroscopy (RLSCS). RLSCS is based on the correlation analysis of the fluctuations of resonance light scattering due to Brownian motion of single nanoparticles in a highly-focused laser volume. Similar to single molecule fluorescence correlation spectroscopy, the number of particles in the detection volume is reciprocally related to the G(0) value in the RLSCS plot. A model is established for quantification of GNP concentration, and the effect of laser illumination intensity was studied. An excellent linear relationship exists between the concentration of GNP and the reciprocal G(0) value of the correlation plots at low laser illumination intensity. The method was applied to the determination of the molar concentrations of GNP in sizes of 15, 20, 30, and 40 nm to give detection limits of 300, 80, 10, and 40 pM, respectively. The results obtained by RLSCS were in good agreement with that of combined atomic emission spectroscopy and transmission electron microscopy (AES-TEM). A sensitive microscale method was reported for the determination of the activity of the enzyme caspase 3 by RLSCS by using GNP as labeling probes. The assay is based on the measurement of the change of the molar concentration of GNP when peptide-labeled GNP substrates were cleaved by caspase 3. The method is shown to enable the determination of caspase 3 (with a 0.1 nM detection limit) and to monitoring drug-induced cell apoptosis.

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“…Our and other's previous studies have shown that LDM-induced cytotoxicity may result from apoptosis and/or cell cycle arrest. 12,18,19 We next investigated the induction of apoptosis and cell cycle distribution changes upon 0.5 nM LDM treatment for 48-120 h with FACS analysis, and found that LDM induced 16.5% and 24.7% apoptosis in HCT116 cells, and 16.9% and 17.5% apoptosis in SW620 cells after treatment for 72 h and 96 h, respectively (Supplementary Figure S1a). Furthermore, LDM induced more significant G2/M phase arrest in both time-and dosedependent manner, reaching nearly 90% G2/M phase after drug treatment for 120 h ( Figure 3a).…”

Section: Resultsmentioning

confidence: 99%

EZH2 mediates lidamycin-induced cellular senescence through regulating p21 expression in human colon cancer cells

Wang¹,

Sha²,

Zhao³

et al. 2016

European Journal of Cancer

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P53 dependent and independent apoptosis induced by lidamycin in human colorectal cancer cells

Cited by 23 publications

References 41 publications

Knockdown of Chk1 sensitizes human colon carcinoma HCT116 cells in a p53-dependent manner to lidamycin through abrogation of a G2/M checkpoint and induction of apoptosis

Knockdown of Chk1 sensitizes human colon carcinoma HCT116 cells in a p53-dependent manner to lidamycin through abrogation of a G2/M checkpoint and induction of apoptosis

A single particle method for direct determination of molar concentrations of gold nanoparticles, and its application to the determination of the activity of caspase 3 and drug-induced cell apoptosis

EZH2 mediates lidamycin-induced cellular senescence through regulating p21 expression in human colon cancer cells

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