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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 oncosis was not interfered by neither apoptosis inhibitor nor necrosis inhibitor and no caspase-3 activation was detected under QC2 treatment. (a) No significant change of cell viability was detected when SMMC-7721 cells were pretreated with or without z-VAD-FMK or necrostatin (P > 0.05). (b) As QC2 concentration increased, no cleaved-caspase-3 was detected while it appeared in 200 μg/mL carboplatin treated cells.
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fig5: QC2 induced oncosis was not interfered by neither apoptosis inhibitor nor necrosis inhibitor and no caspase-3 activation was detected under QC2 treatment. (a) No significant change of cell viability was detected when SMMC-7721 cells were pretreated with or without z-VAD-FMK or necrostatin (P > 0.05). (b) As QC2 concentration increased, no cleaved-caspase-3 was detected while it appeared in 200 μg/mL carboplatin treated cells.

Mentions: As an executioner caspase, caspase-3 plays a crucial role both in extrinsic (death ligand) and intrinsic (mitochondrial) apoptosis pathways [12, 13]. Blockage of caspase-3 by its inhibitor z-VAD-fmk could abolish the apoptotic events; the same thing would happen in necrosis by necrostatin [14]. To further distinguish oncosis from apoptosis and necrosis, we pretreated cells with z-VAD-fmk (50μM) or necrostatin (500 nM) before QC2 treatment. Results came out that no statistical difference was detected when using z-VAD-fmk or necrostatin (Figures 5(a) and 5(b)). During the protein detection, carboplatin was set as the positive control for activated caspase-3 detection but no such activated caspase-3 was found in the QC2 groups (Figure 5(c)). All these results suggested that the oncosis induced by QC2 in SMMC-7721 cells was different from apoptosis and necrosis.


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 oncosis was not interfered by neither apoptosis inhibitor nor necrosis inhibitor and no caspase-3 activation was detected under QC2 treatment. (a) No significant change of cell viability was detected when SMMC-7721 cells were pretreated with or without z-VAD-FMK or necrostatin (P > 0.05). (b) As QC2 concentration increased, no cleaved-caspase-3 was detected while it appeared in 200 μg/mL carboplatin treated cells.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4109319&req=5

fig5: QC2 induced oncosis was not interfered by neither apoptosis inhibitor nor necrosis inhibitor and no caspase-3 activation was detected under QC2 treatment. (a) No significant change of cell viability was detected when SMMC-7721 cells were pretreated with or without z-VAD-FMK or necrostatin (P > 0.05). (b) As QC2 concentration increased, no cleaved-caspase-3 was detected while it appeared in 200 μg/mL carboplatin treated cells.
Mentions: As an executioner caspase, caspase-3 plays a crucial role both in extrinsic (death ligand) and intrinsic (mitochondrial) apoptosis pathways [12, 13]. Blockage of caspase-3 by its inhibitor z-VAD-fmk could abolish the apoptotic events; the same thing would happen in necrosis by necrostatin [14]. To further distinguish oncosis from apoptosis and necrosis, we pretreated cells with z-VAD-fmk (50μM) or necrostatin (500 nM) before QC2 treatment. Results came out that no statistical difference was detected when using z-VAD-fmk or necrostatin (Figures 5(a) and 5(b)). During the protein detection, carboplatin was set as the positive control for activated caspase-3 detection but no such activated caspase-3 was found in the QC2 groups (Figure 5(c)). All these results suggested that the oncosis induced by QC2 in SMMC-7721 cells was different from apoptosis and necrosis.

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