Oridonin nanosuspension was more effective than free oridonin on G2/M cell cycle arrest and apoptosis in the human pancreatic cancer PANC-1 cell line

Abstract

Oridonin, a diterpenoid isolated from Rabdosia rubescencs, has been reported to have antitumor effects. However, low solubility has limited its clinical applications. Preparation of drugs in the form of nanosuspensions is an extensively utilized protocol. In this study, we investigated the anticancer activity of oridonin and oridonin nanosuspension on human pancreatic carcinoma PANC-1 cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to investigate the effect of oridonin on cell growth. Propidium iodide and Hoechst 33342 staining were used to detect morphologic changes. The percentage of apoptosis and cell cycle progression was determined by flow cytometric method staining with propidium iodide. Annexin V-fluorescein isothiocyanate (FITC)/PI staining was used to evaluate cell apoptosis by flow cytometry. Caspase-3 activity was measured by spectrophotometry. The apoptotic and cell cycle protein expression were determined by Western blot analysis. Both oridonin and oridonin nanosuspension induced apoptosis and G 2 /M phase cell cycle arrest, and the latter had a more significant cytotoxic effect. The ratio of Bcl-2/Bax protein expression was decreased and caspase-3 activity was stimulated. The expression of cyclin B1 and p-cdc2 (T161) was suppressed. Our results showed that oridonin nanosuspension was more effective than free oridonin on G 2 /M cell cycle arrest and apoptosis in the human pancreatic cancer PANC-1 cell line.

Oridonin, a novel lysine acetyltransferases inhibitor, inhibits proliferation and induces apoptosis in gastric cancer cells through p53- and caspase-3-mediated mechanisms

“…It has been reported to have tolerable toxicities in vivo [6] and possess anti-tumor activities in a variety of human malignancies such as leukemia [7], liver cancer [8], pancreatic cancer [9], fibrosarcoma [10] and cervical cancer [11]. In our preliminary study, oridonin was found to possess acetyltransferase-inhibitory effects.…”

Discovery and development of natural product oridonin-inspired anticancer agents

“…Consequently, such strategies may also be useful for oridonin and its derivatives to improve drug-likeness. The preparation of oridonin or its active analogs in the form of a nanosuspension can result in enhanced aqueous solubility and efficiency against human cancer cell lines in vitro and in vivo [116–118]. The exploration of novel drug delivery formulations containing nanosuspension, nanogels, nanoparticles, micelles and self-microemulsifying systems would provide aqueous soluble, tumor targeting and potent oridonin-like agents for potential clinical applications [63, 119–123].…”

Phytotherapeutics oridonin and ponicidin show additive effects combined with irradiation in pancreatic cancer in vitro

“…Therefore we did not investigate any changes in proteins of the cell cycle regulation but further experiments should pinpoint the precise mode G2/M-phase arrest induced by oridonin and ponicidin. Since induction of apoptosis was reported for both oridonin and ponicidin 9 , 10 , 11 , 12 , 14 , 15 , 16 , 17 we expected a sub-G1 peak in cell cycle analysis but could not observe any peak in the sub-G1 noise. Interestingly, the cell cycle assays of Qi et al .…”

“…for the pancreatic cancer cell line Panc-1 along with a suppression of cell cycle regulating cyclin B1 and cdc2. 10 In our study, we focused on DNA double-strand breaks as underlying mechanism especially after combination with irradiation. Therefore we did not investigate any changes in proteins of the cell cycle regulation but further experiments should pinpoint the precise mode G2/M-phase arrest induced by oridonin and ponicidin.…”

“… 6 , 7 , 8 In pancreatic cancer oridonin induces apoptosis and leads to an arrest in the G2/M-phase of the cell cycle. 9 , 10 , 11 , 12 Further, oridonin inhibits nuclear factor-kB. 13 Ponicidin is also known to induce apoptosis 14 , 15 , 16 , 17 but to our knowledge, there is no data for ponicidin in pancreatic cancer.…”