Ottelione A inhibited proliferation of Ehrlich ascites carcinoma cells in mice

Abstract

While the main target of chemotherapy in cancer treatment is the induction of apoptosis and cell death, natural products provide a wealth to medicine and are considered great sources of new drugs for cancer treatment. We aimed to determine the antitumor effect of ottelione A (OTTE) on the growth and proliferation of Ehrlich ascites carcinoma cells (EACs) implanted i.p. in female mice. Animals were inoculated with EAC cells to serve as the control group. In the OTTE group, animals were implanted with EAC followed by i.p. administration of OTTE. Antitumor activity was evaluated 15days after tumor implantation. The administration of OTTE significantly reduced ascetic volume, viability of EAC cells and increased the survival of tumor-bearing animals. Flow cytometric analysis indicated that OTTE induced G0/G1 cell cycle arrest and apoptosis. These findings were associated with an alteration of redox state of EAC cells, which might impact cascade effects leading to cell cycle arrest at G0/G1 phase. These effects include a decreased expression of cyclin D1, increased p53 expression and down-regulation of rRNA level, stimulation of CD8+ infiltrating T-lymphocytes. In addition, OTTE normalized oxidative stress in the liver of mice-bearing EAC cells evidenced by increased the levels of glutathione, superoxide dismutase, and catalase. In conclusion, the differential expression of p53, cyclin D1, and rRNA in EAC cells as well as the infiltration of CD8+ after OTTE treatment may play critical roles in the G0/G1 cell cycle arrest that blocks cell proliferation and induce apoptosis of cancer cells. The potent antitumor property of the ottelione A can be exploited further to develop therapeutic protocols for treatment of cancer.