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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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Calpain-1 increased during oncosis and its inhibition attenuated the cytotoxicity of QC2. (a) Calpain-1 increased and gradually autolyzed into 76 kDa fragments under QC2 treatment. (b) Significant change of cell viability was observed in SMMC-7721 cells when pretreated with the calpain inhibitor PD150606 (P < 0.05).
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fig7: Calpain-1 increased during oncosis and its inhibition attenuated the cytotoxicity of QC2. (a) Calpain-1 increased and gradually autolyzed into 76 kDa fragments under QC2 treatment. (b) Significant change of cell viability was observed in SMMC-7721 cells when pretreated with the calpain inhibitor PD150606 (P < 0.05).

Mentions: Various studies have found that calpain, a kind of calcium-dependent thiol proteinase, mediated the oncotic event in different cells. Researchers have found that calpain increased before membrane damage and inhibition of calpain could protect cells from cell death [15], but whether calpain-1 or calpain-2 was involved remained unknown. In our study, we confirmed the activation of calpain-1 in QC2-treated cells by detecting the level of this protein. As shown in Figure 7(a), calpain-1 increased and the protein autolyzed from the molecular weight of 80 kDa to 76 kDa when treated with QC2. The increased calpain-1 level might imply the activation of this protein during the oncotic cell death. In the subsequent experiment, the calpain inhibitor PD150606 was adopted. To our delight, 100 μM PD150606 partially abrogated the cytotoxicity of QC2 at the concentration of 3 μg/mL (Figure 7(b)).


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)

Calpain-1 increased during oncosis and its inhibition attenuated the cytotoxicity of QC2. (a) Calpain-1 increased and gradually autolyzed into 76 kDa fragments under QC2 treatment. (b) Significant change of cell viability was observed in SMMC-7721 cells when pretreated with the calpain inhibitor PD150606 (P < 0.05).
© Copyright Policy
Related In: Results  -  Collection

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

fig7: Calpain-1 increased during oncosis and its inhibition attenuated the cytotoxicity of QC2. (a) Calpain-1 increased and gradually autolyzed into 76 kDa fragments under QC2 treatment. (b) Significant change of cell viability was observed in SMMC-7721 cells when pretreated with the calpain inhibitor PD150606 (P < 0.05).
Mentions: Various studies have found that calpain, a kind of calcium-dependent thiol proteinase, mediated the oncotic event in different cells. Researchers have found that calpain increased before membrane damage and inhibition of calpain could protect cells from cell death [15], but whether calpain-1 or calpain-2 was involved remained unknown. In our study, we confirmed the activation of calpain-1 in QC2-treated cells by detecting the level of this protein. As shown in Figure 7(a), calpain-1 increased and the protein autolyzed from the molecular weight of 80 kDa to 76 kDa when treated with QC2. The increased calpain-1 level might imply the activation of this protein during the oncotic cell death. In the subsequent experiment, the calpain inhibitor PD150606 was adopted. To our delight, 100 μM PD150606 partially abrogated the cytotoxicity of QC2 at the concentration of 3 μg/mL (Figure 7(b)).

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