Anemarrhena asphodeloides Bunge and its constituent timosaponin‐AIII induce cell cycle arrest and apoptosis in pancreatic cancer cells

Pancreatic cancer is one of the most recalcitrant and lethal of all cancers. We examined the effects of Anemarrhena asphodeloides (AA) and timosaponin‐AIII (TAIII), a steroidal saponin present in AA, on pancreatic cancer cell proliferation and aimed to elucidate their potential apoptotic mechanisms...

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Veröffentlicht in:FEBS open bio 2018-07, Vol.8 (7), p.1155-1166
Hauptverfasser: MarElia, Catherine B., Sharp, Arielle E., Shemwell, Tiffany A., Clare Zhang, Y., Burkhardt, Brant R.
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Sprache:eng
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Zusammenfassung:Pancreatic cancer is one of the most recalcitrant and lethal of all cancers. We examined the effects of Anemarrhena asphodeloides (AA) and timosaponin‐AIII (TAIII), a steroidal saponin present in AA, on pancreatic cancer cell proliferation and aimed to elucidate their potential apoptotic mechanisms of action. Viability assays and cell cycle analysis revealed that both AA and TAIII significantly inhibited pancreatic cancer cell proliferation and cell cycle progression compared to treatment with gemcitabine, the standard chemotherapeutic agent for advanced pancreatic cancer. We identified a dose‐dependent increase in caspase‐dependent apoptosis and activation of pro‐apoptotic PI3K/Akt pathway proteins, with a subsequent downregulation of pro‐survival PI3K/Akt pathway proteins, in pancreatic cancer cells treated with AA or TAIII over those treated with gemcitabine. We investigated the effects of an Anemarrhena asphodeloides (AA) extract and one of its constituents, timosaponin‐AIII (TAIII), on pancreatic cancer cells. We observed significant dose‐dependent reductions in viability and cell cycle progression, caspase‐dependent apoptosis, and differential phosphorylation of Akt pathway proteins. These results suggest that AA and TAIII inhibit the ability of pancreatic cancer cells to survive and resist chemotherapeutic intervention.
ISSN:2211-5463
2211-5463
DOI:10.1002/2211-5463.12457