The synthesized 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one (CHM-1) promoted G2/M arrest through inhibition of CDK1 and induced apoptosis through the mitochondrial-dependent pathway in CT-26 murine colorectal adenocarcinoma cells

Chou, Li Chen; Yang, Jai Sing; Huang, Li Jiau; Wu, Hsi Chin; Lu, Chi‐Cheng; Chiang, Jen‐Huai; Chen, Kuan Tin; Kuo, Sheng Chu; Chung, Jing Gung

doi:10.1007/s00535-009-0111-1

Cited by 29 publications

(26 citation statements)

References 20 publications

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“…Cytochrome C is released from the intermembrane space of mitochondria into the cytosol and activates the caspase-9 proenzyme, which, in turn, activates caspase-3, which cleaves PARP to initiate a caspase cascade leading to apoptosis. 29,50 Our results were in agreement with those of previous studies. We also observed that the translocation of BAX and cytochrome C might be because BAX proteins anchor to the mitochondria, whereas cytochrome C is released following SDT.…”

supporting

confidence: 94%

“…Six hours after SDT, macrophages were loaded with 5 μM calcein-AM (GenMed Scientifics Inc., Wilmington, DE, USA) in the presence of 5 mM cobalt chloride in the dark for 20 minutes at 37°C as previously described. 29 The cells were carefully washed twice with PBS, and fluorescence was monitored via fluorescence microscopy. Calcein-AM fluorescence was measured at 525 nm following excitation at 488 nm.…”

Section: Measurement Of Changes In the Mptpmentioning

confidence: 99%

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The efficacy and mechanism of apoptosis induction by hypericin-mediated sonodynamic therapy in THP-1 macrophages

Li¹,

Gao²,

Zheng³

et al. 2015

IJN

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Purpose To investigate the sonoactivity of hypericin (HY), together with its sonodynamic effect on THP-1 macrophages and the underlying mechanism. Materials and methods CCK-8 was used to examine cell viability. Confocal laser scanning microscopy was performed to assess the localization of HY in cells, reactive oxygen species (ROS) generation, and opening of the mitochondrial permeability transition pore (mPTP) after different treatments. Apoptosis was analyzed using Hoechst–propidium iodide and transmission electron microscopy. Mitochondrial membrane potential (ΔΨm) collapse was detected via fluorescence microscopy. Lipoprotein oxidation was determined in malondialdehyde (MDA) assays. Western blotting was conducted to determine the translocation of BAX and cytochrome C and the expression of apoptosis-related proteins. Results HY was sublocalized among the nuclei and the mitochondria, endoplasmic reticulum, Golgi apparatus, and lysosome in the cytosol of THP-1 macrophages. Under low-intensity ultrasound irradiation, HY significantly decreased cell viability and induced apoptosis. Furthermore, greater ROS generation, higher MDA levels, and greater ΔΨm loss were observed in the sonodynamic therapy (SDT) group. Both ROS generation and MDA levels were significantly reduced by the ROS scavenger N-acetyl cysteine (NAC) and the singlet oxygen scavenger sodium azide. Most of the loss of ΔΨm was inhibited by pretreatment with NAC, sodium azide, and the mPTP inhibitor cyclosporin A (CsA). mPTP opening was induced upon SDT but was reduced by pretreatment with bongkrekic acid, 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid disodium, CsA, and NAC. Western blot analyses revealed translocation of BAX and cytochrome C, downregulated expression of Bcl-2, and upregulated expression of cleaved caspase-9, cleaved caspase-3, and cleaved poly(ADP-ribose) polymerase in the SDT group, which were reversed by NAC. Conclusion HY mediated SDT-induced apoptosis in THP-1 macrophages via ROS generation. Then, the proapoptotic factor BAX translocated from the cytosol to the mitochondria, increasing the ratio of BAX/Bcl-2, and the mPTP opened to release cytochrome C. This study demonstrated the great potential of HY-mediated SDT for treating atherosclerosis.

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supporting

confidence: 94%

Section: Measurement Of Changes In the Mptpmentioning

confidence: 99%

The efficacy and mechanism of apoptosis induction by hypericin-mediated sonodynamic therapy in THP-1 macrophages

Li¹,

Gao²,

Zheng³

et al. 2015

IJN

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“…About 6 h after the PDT treatment, the cells were stained with 5 µM calcein AM (GenMed Scientifics Inc., Arlington, MA, USA) in the presence of 5 mM cobalt chloride in the dark for 20 minutes at 37°C, as previously described. 21 The cells were then carefully washed twice with PBS. Fluorescence was examined using a fluorescence microscope (Olympus IX81, Olympus Corporation), and the change in MPTP following the PDT treatment was also determined using the same method.…”

Section: Detection Of Mptp Changesmentioning

confidence: 99%

Upconversion nanoparticle-mediated photodynamic therapy induces THP-1 macrophage apoptosis via ROS bursts and activation of the mitochondrial caspase pathway

Zhu¹,

Wang²,

Zheng³

et al. 2015

IJN

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Atherosclerosis (AS) is the most vital cardiovascular disease, which poses a great threat to human health. Macrophages play an important role in the progression of AS. Photodynamic therapy (PDT) has emerged as a useful therapeutic modality not only in the treatment of cancer but also in the treatment of AS. The purpose of this study was to determine the molecular mechanisms underlying the activity of PDT, using mesoporous-silica-coated upconversion fluorescent nanoparticles encapsulating chlorin e6 (UCNPs-Ce6) in the induction of apoptosis in THP-1 macrophages. Here, we investigated the ability of UCNPs-Ce6-mediated PDT to induce THP-1 macrophage apoptosis by facilitating the induction of reactive oxygen species (ROS) and regulation of mitochondrial permeability transition pore (MPTP) to depolarize mitochondrial membrane potential (MMP). Both Bax translocation and the release of cytochrome C were examined using immunofluorescence and Western blotting. Our results indicated that the levels of ROS were significantly increased in the PDT group, resulting in both MPTP opening and MMP depolarization, which led to apoptosis. In addition, immunofluorescence and Western blotting revealed that PDT induced both Bax translocation and the release of cytochrome C, as well as upregulation of cleaved caspase-9, cleaved caspase-3, and cleaved poly(ADP-ribose) polymerase. Therefore, we demonstrated that UCNPs-Ce6-mediated PDT induces apoptosis in THP-1 macrophages via ROS bursts. The proapoptotic factor Bax subsequently translocates from the cytosol to the mitochondria, resulting in the MPTP opening and cytochrome C release. This study demonstrated the great potential of UCNPs-Ce6-mediated PDT in the treatment of AS.

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“…It was also reported that the G2/M checkpoint plays an important role for DNA damage-induced apoptosis. The CDK1/Cyclin B complex is the major regulator leading the G2 to M phase progression (2,9). Recently, it was reported that p21, a potent cyclin-dependent kinase inhibitor (CKI), is a key regulator, and it can inhibit the CDK1 activity and strengthen the G2/M arrest of cell cycle distribution (15,31).…”

Section: Discussionmentioning

confidence: 99%

“…Induction of cell cycle arrest and apoptosis in tumor cells may be a considered strategy for colon cancer. The process of cell cycle has been investigated frequently, particularly CDK1/Cyclin B complex play an important role for regulation of G2/M phase (2,3). Much evidence shows that tumor cells can be induced to cell death through cell arrest and apoptosis (4,5).…”

Section: Introductionmentioning

confidence: 99%

Cantharidin induces G2/M phase arrest and apoptosis in human colorectal cancer colo 205 cells through inhibition of CDK1 activity and caspase-dependent signaling pathways

Chen¹

2011

Int J Oncol

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Abstract. Cantharidin (CTD) is a traditional Chinese medicine and an effective component isolated from blister beetle, and it has been demonstrated to have anticancer, antibiotic, antivirus activities and immune-regulated functions. It has been reported that CTD induces cell cycle arrest and apoptosis in many cancer cell types. However, there are no reports showing that CTD would induce cell cycle arrest and apoptosis in human colorectal cancer colo 205 cells. In this study, we studied colo 205 cells which were treated with CTD and demonstrated its molecular mechanisms in apoptosis. CTD induced growth inhibition, G2/M phase arrest and apoptosis in colo 205 cells. The IC 50 is 20.53 µM in CTD-treated colo 205 cells. DAPI/TUNEL double staining and Annexin V assays were used to confirm the apoptotic cell death in colo 205 cells after CTD exposure. CTD caused G2/M arrest, down-regulated CDK1 activity, decreased Cyclin A, Cyclin B, CDK1 and increased CHK1 and p21 protein levels. Colorimetric assays also indicated that CTD triggered activities of casapse-8, -9 and -3 in colo 205 cells. Moreover, CTD increased ROS production and decreased the level of mitochondrial membrane potential (ΔΨm) in colo 205 cells. Consequently, CTD-induced growth inhibition was significantly attenuated by N-acetylcysteine (NAC, a scavenger). CTD stimulated the protein levels of Fas/CD95, the caspase-3 active form, cytochrome c and Bax, but suppressed the protein levels of pro-caspase-8, pro-caspase-9 and Bcl-2, determined by Western blot analysis. Based on our observations, we suggest that CTD is able to induce G2/M phase arrest and apoptosis in colo 205 cells through inhibition of CDK1 activity and caspase-dependent signaling pathways.

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The synthesized 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one (CHM-1) promoted G2/M arrest through inhibition of CDK1 and induced apoptosis through the mitochondrial-dependent pathway in CT-26 murine colorectal adenocarcinoma cells

Abstract: Taken together, CHM-1 acted against colorectal adenocarcinoma cells in vitro via G2/M arrest and apoptosis, and CHM-1-P inhibited tumor growth in vivo.

Cited by 29 publications

References 20 publications

The efficacy and mechanism of apoptosis induction by hypericin-mediated sonodynamic therapy in THP-1 macrophages

The efficacy and mechanism of apoptosis induction by hypericin-mediated sonodynamic therapy in THP-1 macrophages

Upconversion nanoparticle-mediated photodynamic therapy induces THP-1 macrophage apoptosis via ROS bursts and activation of the mitochondrial caspase pathway

Cantharidin induces G2/M phase arrest and apoptosis in human colorectal cancer colo 205 cells through inhibition of CDK1 activity and caspase-dependent signaling pathways

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