Dehydroabietic Acid Derivative QC2 Induces Oncosis in Hepatocellular Carcinoma Cells

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.

Nonautophagic cytoplasmic vacuolation death induction in human PC-3M prostate cancer by curcumin through reactive oxygen species -mediated endoplasmic reticulum stress

“…Several forms of nonapoptotic and nonautophagic cell death, such as oncosis 7 , necroptosis 8 , entosis 9 , anoikis 10 , and programmed necrosis 11 , have been described according to specific cellular and molecular criteria. Importantly, two similar types of nonapoptotic and nonautophagic cell death: cytoplasmic vacuolation death and paraptosis have been described based on the specific formation of cytoplasmic vacuoles 12 13 14 .…”

Dehydroabietic Acid Derivative QC4 Induces Gastric Cancer Cell Death via Oncosis and Apoptosis

“…Researches focusing on the synthesis and evaluation of new DHA derivatives are emerging in recent years. Many derivatives of DHA have been reported to have the property of inhibiting cancer cells and bacteria [ 9 – 12 ]. We demonstrated in the present work that the DHA derivative QC4 exerted strong cytotoxicity on gastric cancer cells.…”

“…The ultramicrostructural analysis of QC4-treated cells was conducted following published protocols [ 12 ]. The ultrathin sections were obtained, stained with 1% toluidine blue, and observed by a transmission electron microscope (JEM-1010, Japan).…”

“…They found that many DHA derivatives showed moderate-to-robust inhibitory effects against tumor cells [ 11 ]. The work by Zhang et al studied the cytotoxic effect of N-substituted 1H-dibenzo [a, c]carbazole derivative of DHA on hepatocellular carcinoma (HCC) cells and concluded that this derivative could significantly inhibit HCC cell viability [ 12 ]. These research achievements proved the potential biological activities of DHA derivatives.…”

Synthesis and biological evaluation of novel N-(piperazin-1-yl)alkyl-1H-dibenzo[a,c]carbazole derivatives of dehydroabietic acid as potential MEK inhibitors

“…Subsequently, in the in vitro cytotoxic assay, two compounds (QC2 and QC4) ( Figure 2) of these derivatives exhibited significant antiproliferative activity against hepatocarcinoma and gastric cancer cell lines with IC 50 values at low micromolar level. In pharmacological studies, it was found that QC2 could activate oncosis related protein calpain to induce the damage of cytomembrane and organelles which finally lead to oncosis in hepatocarcinoma cells 36 . QC4 could also induce the oncosis and apoptosis in gastric cancer cells 37 .…”