LY294002 enhances boswellic acid-induced apoptosis in colon cancer cells.
BACKGROUND
Boswellic acids, a type of pentacyclic triterpenoids, have been shown to induce apoptosis in colon cancer cells. The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway is crucial for cell proliferation and survival. Whether the apoptotic effects of boswellic acid could be affected by inhibition of PI3K/Akt pathway was examined.


METHODS
Colon cancer HT29 cells were treated with 3-acetyl-11-keto-beta boswellic acid AKBA in the absence and presence of LY294002 or Wortmanin, inhibitors of PI3K. Apoptosis was determined by flow cytometry and caspase assay. The activation of Akt was examined by Western blot.


RESULTS
AKBA at 30 microM only slightly induced apoptosis. Preincubation of the cells with LY294002 or wortmannin significantly enhanced the AKBA-induced apoptosis up to 20-fold. Further study showed that at the doses used, AKBA induced phosphorylation of Akt at both Ser473 and Thr308 positions, indicating an activation of the PI3K/Akt pathway.


CONCLUSIONS
AKBA may activate the PI3K/Akt pathway and inhibition of the PI3K pathway significantly enhances AKBA-induced apoptosis.
Liu
Jian-Jun
JJ
1Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Republic of Singapore.
Duan
Rui-Dong
RD
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D029743:Boswellia / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D009025:Morpholines / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D014315:Triterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000893:Anti-Inflammatory Agents; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D014315:Triterpenes; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C054625:boswellic acid