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Dehydroabietic acid derivative QC2 induces oncosis in hepatocellular carcinoma cells.

Zhang G, Jiang C, Wang Z, Chen W, Gu W, Ding Y - Biomed Res Int (2014)

Bottom Line: In this report, we investigate the inhibitory effect against HCC cells of QC2, the derivative of rosin's main components dehydroabietic acid.The detection of ROS accumulation, increased LDH release, and decreased ATP and Δψm confirmed the cell death.Dehydroabietic acid derivative QC2 activated oncosis related protein calpain to induce the damage of cytomembrane and organelles which finally lead to oncosis in HCC cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu 210008, China.

ABSTRACT

Aim: Rosin, the traditional Chinese medicine, is reported to be able to inhibit skin cancer cell lines. In this report, we investigate the inhibitory effect against HCC cells of QC2, the derivative of rosin's main components dehydroabietic acid.

Methods: MTT assay was used to determine the cytotoxicity of QC2. Morphological changes were observed by time-lapse microscopy and transmission electron microscopy and the cytoskeleton changes were observed by laser-scanning confocal microscopy. Cytomembrane integrity and organelles damage were confirmed by detection of the reactive oxygen (ROS), lactate dehydrogenase (LDH), and mitochondrial membrane potential (Δψm). The underlying mechanism was manifested by Western blotting. The oncotic cell death was further confirmed by detection of oncosis related protein calpain.

Results: Swelling cell type and destroyed cytoskeleton were observed in QC2-treated HCC cells. Organelle damage was visualized by transmission electron microscopy. The detection of ROS accumulation, increased LDH release, and decreased ATP and Δψm confirmed the cell death. The oncotic related protein calpain was found to increase time-dependently in QC2-treated HCC cells, while its inhibitor PD150606 attenuated the cytotoxicity.

Conclusions: Dehydroabietic acid derivative QC2 activated oncosis related protein calpain to induce the damage of cytomembrane and organelles which finally lead to oncosis in HCC cells.

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Related in: MedlinePlus

QC2 induced destruction of cytomembrane and ultrastructural changes in SMMC-7721 cells. (a) LDH level time-dependently increased in the supernatants of QC2-treated cells. (b) PI uptake of SMMC-7721 cells accumulated along with increase of QC2 concentration. (c) Electron micrographs of QC2-treated SMMC-7721 cells showed ultrastructure changes.
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fig3: QC2 induced destruction of cytomembrane and ultrastructural changes in SMMC-7721 cells. (a) LDH level time-dependently increased in the supernatants of QC2-treated cells. (b) PI uptake of SMMC-7721 cells accumulated along with increase of QC2 concentration. (c) Electron micrographs of QC2-treated SMMC-7721 cells showed ultrastructure changes.

Mentions: LDH would be released into the medium and the nucleus would become easily stained when the cell membrane is destructed. Hence, we evaluated the integrity of cell membrane by LDH release assay and PI uptake. We treated cells with 10 μg/mL QC2 from 0.25 hour to 4 hours. As shown in Figure 3(a), LDH level stayed low during the first 1 hour and increased at 2 hours which suggested a membrane rupture. The dose-dependent PI uptake was in accordance with the LDH release assay. As shown in Figure 3(b), cells retained smooth morphology and no fluorescence was seen in the control group or the low dose groups while cells became swelled and red fluorescence stained by PI in the groups over 2.5 μg/mL.


Dehydroabietic acid derivative QC2 induces oncosis in hepatocellular carcinoma cells.

Zhang G, Jiang C, Wang Z, Chen W, Gu W, Ding Y - Biomed Res Int (2014)

QC2 induced destruction of cytomembrane and ultrastructural changes in SMMC-7721 cells. (a) LDH level time-dependently increased in the supernatants of QC2-treated cells. (b) PI uptake of SMMC-7721 cells accumulated along with increase of QC2 concentration. (c) Electron micrographs of QC2-treated SMMC-7721 cells showed ultrastructure changes.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4109319&req=5

fig3: QC2 induced destruction of cytomembrane and ultrastructural changes in SMMC-7721 cells. (a) LDH level time-dependently increased in the supernatants of QC2-treated cells. (b) PI uptake of SMMC-7721 cells accumulated along with increase of QC2 concentration. (c) Electron micrographs of QC2-treated SMMC-7721 cells showed ultrastructure changes.
Mentions: LDH would be released into the medium and the nucleus would become easily stained when the cell membrane is destructed. Hence, we evaluated the integrity of cell membrane by LDH release assay and PI uptake. We treated cells with 10 μg/mL QC2 from 0.25 hour to 4 hours. As shown in Figure 3(a), LDH level stayed low during the first 1 hour and increased at 2 hours which suggested a membrane rupture. The dose-dependent PI uptake was in accordance with the LDH release assay. As shown in Figure 3(b), cells retained smooth morphology and no fluorescence was seen in the control group or the low dose groups while cells became swelled and red fluorescence stained by PI in the groups over 2.5 μg/mL.

Bottom Line: In this report, we investigate the inhibitory effect against HCC cells of QC2, the derivative of rosin's main components dehydroabietic acid.The detection of ROS accumulation, increased LDH release, and decreased ATP and Δψm confirmed the cell death.Dehydroabietic acid derivative QC2 activated oncosis related protein calpain to induce the damage of cytomembrane and organelles which finally lead to oncosis in HCC cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu 210008, China.

ABSTRACT

Aim: Rosin, the traditional Chinese medicine, is reported to be able to inhibit skin cancer cell lines. In this report, we investigate the inhibitory effect against HCC cells of QC2, the derivative of rosin's main components dehydroabietic acid.

Methods: MTT assay was used to determine the cytotoxicity of QC2. Morphological changes were observed by time-lapse microscopy and transmission electron microscopy and the cytoskeleton changes were observed by laser-scanning confocal microscopy. Cytomembrane integrity and organelles damage were confirmed by detection of the reactive oxygen (ROS), lactate dehydrogenase (LDH), and mitochondrial membrane potential (Δψm). The underlying mechanism was manifested by Western blotting. The oncotic cell death was further confirmed by detection of oncosis related protein calpain.

Results: Swelling cell type and destroyed cytoskeleton were observed in QC2-treated HCC cells. Organelle damage was visualized by transmission electron microscopy. The detection of ROS accumulation, increased LDH release, and decreased ATP and Δψm confirmed the cell death. The oncotic related protein calpain was found to increase time-dependently in QC2-treated HCC cells, while its inhibitor PD150606 attenuated the cytotoxicity.

Conclusions: Dehydroabietic acid derivative QC2 activated oncosis related protein calpain to induce the damage of cytomembrane and organelles which finally lead to oncosis in HCC cells.

Show MeSH
Related in: MedlinePlus