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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

ATP deletion, Δψm collapse, and ROS generation were observed in oncotic cells. ((a) and (b)) ATP and Δψm level generally decreased in 10 μg/mL QC2-treated SMMC-7721 cells time-dependently. (c) ROS accumulation was detected in QC2-treated cells.
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fig6: ATP deletion, Δψm collapse, and ROS generation were observed in oncotic cells. ((a) and (b)) ATP and Δψm level generally decreased in 10 μg/mL QC2-treated SMMC-7721 cells time-dependently. (c) ROS accumulation was detected in QC2-treated cells.

Mentions: Researchers have found that oncosis started with ATP depletion; then, ion pumps were influenced and Δψm collapsed [15]. As an indicator of mitochondria damage, ROS was also detected. ATP decreased time-dependently as well as Δψm (Figures 6(a) and 6(b)). Compared to the positive control, 5 mg/mL Rosup, the QC2-treated cells showed a similar tendency of ROS accumulation (Figure 6(c)). ROS generation and mitochondrial membrane changes were also key events in apoptosis and necrosis; however, ATP depletion emerged only in oncosis. The ATP depletion detected in our research confirmed QC2 induced oncosis in HCC cells.


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)

ATP deletion, Δψm collapse, and ROS generation were observed in oncotic cells. ((a) and (b)) ATP and Δψm level generally decreased in 10 μg/mL QC2-treated SMMC-7721 cells time-dependently. (c) ROS accumulation was detected in QC2-treated cells.
© Copyright Policy
Related In: Results  -  Collection

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

fig6: ATP deletion, Δψm collapse, and ROS generation were observed in oncotic cells. ((a) and (b)) ATP and Δψm level generally decreased in 10 μg/mL QC2-treated SMMC-7721 cells time-dependently. (c) ROS accumulation was detected in QC2-treated cells.
Mentions: Researchers have found that oncosis started with ATP depletion; then, ion pumps were influenced and Δψm collapsed [15]. As an indicator of mitochondria damage, ROS was also detected. ATP decreased time-dependently as well as Δψm (Figures 6(a) and 6(b)). Compared to the positive control, 5 mg/mL Rosup, the QC2-treated cells showed a similar tendency of ROS accumulation (Figure 6(c)). ROS generation and mitochondrial membrane changes were also key events in apoptosis and necrosis; however, ATP depletion emerged only in oncosis. The ATP depletion detected in our research confirmed QC2 induced oncosis in HCC cells.

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