Abstract
Introduction Oleandrin, a cardiac glycoside, exerts strong anti-proliferative activity against various human malignancies in in vitro cells. Here, we report the antitumor efficacy of PBI-05204, a supercritical C02 extract of Nerium oleander containing oleandrin, in a human pancreatic cancer Panc-1 orthotopic model. Results While all the control mice exhibited tumors by the end of treatment, only 2 of 8 mice (25 %) treated for 6 weeks with PBI-05204 (40 mg/kg) showed dissectible tumor at the end of the treatment period. The average tumor weight (222.9±116.9 mg) in mice treated with PBI-05204 (20 mg/kg) was significantly reduced from that in controls (920.0±430.0 mg) (p<0.05). Histopathologic examination of serial sections from each pancreas with no dissectible tumor in the PBI-05204 (40 mg/kg) treated group showed that the pancreatic tissues of 5/6 mice were normal while the remaining mouse had a tumor the largest diameter of which was less than 2.3 mm. In contrast, while gemcitabine alone did not significantly reduce tumor growth, PBI-05204 markedly enhanced the antitumor efficacy of gemcitabine in this particular model. Ki-67 staining was reduced in pancreatic tumors from mice treated with PBI-05204 (20 mg/kg) compared to that of control, suggesting that PBI-05204 inhibited the proliferation of the Panc-1 tumor cells. PBI-05204 suppressed expression of pAkt, pS6, and p4EPB1 in a concentration-dependent manner in both Panc-1 tumor tissues and human pancreatic cancer cell lines, implying that this novel botanical drug exerts its potent antitumor activity, at least in part, through down-regulation of PI3k/Akt and mTOR pathways.
Original language | English (US) |
---|---|
Pages (from-to) | 271-279 |
Number of pages | 9 |
Journal | Investigational New Drugs |
Volume | 33 |
Issue number | 2 |
DOIs | |
State | Published - Apr 1 2015 |
Keywords
- Nerium oleander
- Orthotopic
- PBI-05204
- PI3K/mTOR
- Panc-1
ASJC Scopus subject areas
- Oncology
- Pharmacology
- Pharmacology (medical)
MD Anderson CCSG core facilities
- Research Animal Support Facility
- Small Animal Imaging Facility
- Tissue Biospecimen and Pathology Resource