Limits...
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.

Show MeSH

Related in: MedlinePlus

Synthetic route of compound QC2 (6) from dehydroabietic acid (1). Reagents and conditions: (a) (i) SOCl2, benzene, reflux, and 3 h; (ii) MeOH, reflux, and 2 h; (b) CrO3, AcOH, Ac2O, 0°C to rt, and 12 h; (c) phenylhydrazine hydrochloride, EtOH, conc. HCl, reflux, and 3 h; (d) 1,2-dibromoethane, TBAB, NaOH, benzene, rt, and 12 h; (e) piperazine, K2CO3, KI, MeCN, reflux, and 8 h.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4109319&req=5

sch1: Synthetic route of compound QC2 (6) from dehydroabietic acid (1). Reagents and conditions: (a) (i) SOCl2, benzene, reflux, and 3 h; (ii) MeOH, reflux, and 2 h; (b) CrO3, AcOH, Ac2O, 0°C to rt, and 12 h; (c) phenylhydrazine hydrochloride, EtOH, conc. HCl, reflux, and 3 h; (d) 1,2-dibromoethane, TBAB, NaOH, benzene, rt, and 12 h; (e) piperazine, K2CO3, KI, MeCN, reflux, and 8 h.

Mentions: QC2 (Figure 1) is an N-substituted 1H-dibenzo[a,c]carbazole derivative synthesized from dehydroabietic acid. The synthetic route of compound QC2 is illustrated in Scheme 1 and the detailed methods could be found in the paper of Gu and coworkers [10].


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)

Synthetic route of compound QC2 (6) from dehydroabietic acid (1). Reagents and conditions: (a) (i) SOCl2, benzene, reflux, and 3 h; (ii) MeOH, reflux, and 2 h; (b) CrO3, AcOH, Ac2O, 0°C to rt, and 12 h; (c) phenylhydrazine hydrochloride, EtOH, conc. HCl, reflux, and 3 h; (d) 1,2-dibromoethane, TBAB, NaOH, benzene, rt, and 12 h; (e) piperazine, K2CO3, KI, MeCN, reflux, and 8 h.
© Copyright Policy
Related In: Results  -  Collection

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

sch1: Synthetic route of compound QC2 (6) from dehydroabietic acid (1). Reagents and conditions: (a) (i) SOCl2, benzene, reflux, and 3 h; (ii) MeOH, reflux, and 2 h; (b) CrO3, AcOH, Ac2O, 0°C to rt, and 12 h; (c) phenylhydrazine hydrochloride, EtOH, conc. HCl, reflux, and 3 h; (d) 1,2-dibromoethane, TBAB, NaOH, benzene, rt, and 12 h; (e) piperazine, K2CO3, KI, MeCN, reflux, and 8 h.
Mentions: QC2 (Figure 1) is an N-substituted 1H-dibenzo[a,c]carbazole derivative synthesized from dehydroabietic acid. The synthetic route of compound QC2 is illustrated in Scheme 1 and the detailed methods could be found in the paper of Gu and coworkers [10].

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