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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 cell death in HCC and human hepatocytes. (a) QC2 exerted cytotoxicity in four HCC cell lines as well as in human hepatocytes; the IC50 values were 0.37 μg/mL, 1.17 μg/mL, 3 μg/mL, 2.67 μg/mL, and 4.22 μg/mL, respectively. (b) QC2 induced cell death in SMMC-7721 cells was testified by flow cytometry. (c) QC2 dose-dependently induced morphological changes in SMMC-7721 cells.
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fig2: QC2 induced cell death in HCC and human hepatocytes. (a) QC2 exerted cytotoxicity in four HCC cell lines as well as in human hepatocytes; the IC50 values were 0.37 μg/mL, 1.17 μg/mL, 3 μg/mL, 2.67 μg/mL, and 4.22 μg/mL, respectively. (b) QC2 induced cell death in SMMC-7721 cells was testified by flow cytometry. (c) QC2 dose-dependently induced morphological changes in SMMC-7721 cells.

Mentions: We studied the cytotoxicity of QC2 on SMMC-7721, Hep3B, HepG2, and Huh7 by MTT assay and flow cytometry (Figures 2(a) and 2(b)). Of all the four HCC cell lines, QC2 showed high cytotoxicity that 5 μg/mL QC2 was lethal to most HCC cells. The IC50 values of four HCC cell lines were 0.37 μg/mL for Hep3B cells, 1.17 μg/mL for HepG2 cells, 3 μg/mL for Huh7 cells, and 2.67 μg/mL for SMMC-7721 cells, respectively. The IC50 value for LO2 cells was higher: 4.22 μg/mL. Something interesting was that Huh7 cells and SMCC-7721 died at the concentration of 5 μg/mL while nearly all cells survived at 2.5 μg/mL. During the cytotoxicity determination, we also observed the morphologic change. Time-lapse microscopy showed that cells membrane became incomplete and cells swelling happened after plasma membrane blebbing appeared (Figure 2(c)).


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 cell death in HCC and human hepatocytes. (a) QC2 exerted cytotoxicity in four HCC cell lines as well as in human hepatocytes; the IC50 values were 0.37 μg/mL, 1.17 μg/mL, 3 μg/mL, 2.67 μg/mL, and 4.22 μg/mL, respectively. (b) QC2 induced cell death in SMMC-7721 cells was testified by flow cytometry. (c) QC2 dose-dependently induced morphological changes in SMMC-7721 cells.
© Copyright Policy
Related In: Results  -  Collection

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

fig2: QC2 induced cell death in HCC and human hepatocytes. (a) QC2 exerted cytotoxicity in four HCC cell lines as well as in human hepatocytes; the IC50 values were 0.37 μg/mL, 1.17 μg/mL, 3 μg/mL, 2.67 μg/mL, and 4.22 μg/mL, respectively. (b) QC2 induced cell death in SMMC-7721 cells was testified by flow cytometry. (c) QC2 dose-dependently induced morphological changes in SMMC-7721 cells.
Mentions: We studied the cytotoxicity of QC2 on SMMC-7721, Hep3B, HepG2, and Huh7 by MTT assay and flow cytometry (Figures 2(a) and 2(b)). Of all the four HCC cell lines, QC2 showed high cytotoxicity that 5 μg/mL QC2 was lethal to most HCC cells. The IC50 values of four HCC cell lines were 0.37 μg/mL for Hep3B cells, 1.17 μg/mL for HepG2 cells, 3 μg/mL for Huh7 cells, and 2.67 μg/mL for SMMC-7721 cells, respectively. The IC50 value for LO2 cells was higher: 4.22 μg/mL. Something interesting was that Huh7 cells and SMCC-7721 died at the concentration of 5 μg/mL while nearly all cells survived at 2.5 μg/mL. During the cytotoxicity determination, we also observed the morphologic change. Time-lapse microscopy showed that cells membrane became incomplete and cells swelling happened after plasma membrane blebbing appeared (Figure 2(c)).

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