Phospholipase A2 (PLA2), Cyclooxygenase (COX) and 5-Lipoxygenase (5-LOX) are arachidonic acid metabolizing enzymes
and their inhibitors have been developed as therapeutic molecules for cancer and inflammation related disorders. In the present study,
PLA2, COX 1&2 and 5-LOX inhibitory studies of Borassus flabellifer seed coat extract were carried out and substantial 5-LOX
inhibitory activity was found. Dammarane triterpenoid 1 (Dammara-20,23-diene-3,25-diol) was isolated according to 5-LOX activity
guided isolation, and screened for COX (1 & 2) inhibitory activities. Dammarane triterpenoid 1 inhibited carrageenan-induced rat paw edema
and TNF-α secretion levels in lipopolysaccharide (LPS)-induced THP-1 human monocytes. Anticancer activity studies demonstrated the
antiproliferative effect of dammarane triterpenoid 1 on various cancer cell lines including MIA PaCa-2 pancreatic, DU145 prostate,
HL-60 leukemia and Caco-2 colon cancers. Dammarane triterpenoid 1 showed good antiproliferative activity on MIA PaCa-2 pancreatic
cancer cell line with IC50 of 12.36±0.33 µM, among other tested cell lines. Apoptosis inducing activity of dammarane triterpenoid 1 was
confirmed based on increased sub-G0 phase cell population in cell cycle analysis, loss of mitochondrian membrane potential, elevated
levels of cytochrome c, nuclear morphological changes and DNA fragmentation in MIA PaCa-2 pancreatic cancer cells. Therefore,
dammarane triterpenoid skeleton may raise the hope of developing novel anti-inflammatory and anticancer drugs in the future.
Keywords: Anticancer activity, Anti-inflammatory activity, Apoptosis inducing activity, Borassus flabellifer Seed coat, Dammarane
triterpenoid 1, 5-LOX and COX dual inhibitor.
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