Abstract
Aim. QC4 is the derivative of rosin's main components dehydroabietic acid (DHA). We investigated the cytotoxic effect of QC4 on gastric cancer cells and revealed the mechanisms beneath the induction of cell death. Methods. The cytotoxic effect of QC4 on gastric cancer cells was evaluated by CCK-8 assay and flow cytometry. The underlying mechanisms were tested by administration of cell death related inhibitors and detection of apoptotic and oncosis related proteins. Cytomembrane integrity and organelles damage were confirmed by lactate dehydrogenase (LDH) leakage assay, mitochondrial function test, and cytosolic free Ca2+ concentration detection. Results. QC4 inhibited cell proliferation dose- and time-dependently and destroyed cell membrane integrity, activated calpain-1 autolysis, and induced apoptotic protein cleavage in gastric cancer cells. The detection of decreased ATP and mitochondrial membrane potential, ROS accumulation, and cytosolic free Ca2+ elevation confirmed organelles damage in QC4-treated gastric cancer cells. Conclusions. DHA derivative QC4 induced the damage of cytomembrane and organelles which finally lead to oncosis and apoptosis in gastric cancer cells. Therefore, as a derivative of plant derived small molecule DHA, QC4 might become a promising agent in gastric cancer therapy.
Highlights
Gastric cancer is a frequent malignant tumor in digestive system, its incidence has declined over the past several years in developed countries on account of improvement of people’s lifestyle and environment; it remains a major public health burden as the fifth most common cancer and the third material cause of cancer death worldwide especially in Eastern Asia (i.e., China) [1]
We focused on the specific cell death type caused by QC4 in gastric cancer cells
MGC80-3 (b) two successive autolytic events (80 kDa and 76 kDa) [15], we found that calpain-1 autolyzed from the 80 kDa event to the 76 kDa event when treated with QC4, which might imply the activation of this protein during the oncotic cell death (Figure 4(b))
Summary
Gastric cancer is a frequent malignant tumor in digestive system, its incidence has declined over the past several years in developed countries on account of improvement of people’s lifestyle and environment; it remains a major public health burden as the fifth most common cancer and the third material cause of cancer death worldwide especially in Eastern Asia (i.e., China) [1]. Surgery remains the most curative therapy for gastric cancer. For symptoms of early gastric cancer are frequently less or atypical, a substantial proportion of patients present at advanced stage and lost the opportunity of radical gastrectomy when they see doctors. Treatments for advanced and recurrent gastric cancer incorporate chemotherapy, radiotherapy, and biological therapy. Whereas their outcomes are always unsatisfactory for drug resistance and side effects. The 5-year survival of metastatic gastric cancer patients is not exceeding 10% [2, 3]. It is urgent to develop new cytostatic agents and valid treatments for gastric cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
