title: 5-Lipoxygenase and cyclooxygenase inhibitory dammarane triterpenoid 1 from Borassus flabellifer seed coat inhibits tumor necrosis factor-α secretion in LPSInduced THP-1 human monocytes and induces apoptosis in MIA PaCa-2 pancreatic cancer cells.
abstract: 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.
authors: Nagendra Sastry
authors: NS
authors: Yarla
authors: Rajaram
authors: R
authors: Azad
authors: Mahaboob
authors: M
authors: Basha
authors: Abdul
authors: A
authors: Rajack
authors: D S V G K
authors: DS
authors: Kaladhar
authors: Bharat Kumar
authors: BK
authors: Allam
authors: Rajeswara Rao
authors: RR
authors: Pragada
authors: Krishna Nand
authors: KN
authors: Singh
authors: Sunanda Kumari
authors: SK
authors: K
authors: Reddanna
authors: R
authors: Pallu
authors: Umadevi
authors: U
authors: Parimi
authors: Anupam
authors: A
authors: Bishayee
authors: Department of Biochemistry and Bioinformatics, School of Life Sciences, Institute of Science, GITAM University, Visakhapatnam, India. drdgraoresearchgroup@gmail.com.
authors: Govinda Rao
authors: GR
authors: Duddukuri
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D028023:Arecaceae / Q000737:chemistry*; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D016861:Cyclooxygenase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004487:Edema / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D018922:HL-60 Cells; D006801:Humans; D008070:Lipopolysaccharides; D016859:Lipoxygenase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012639:Seeds / Q000737:chemistry; D014315:Triterpenes / Q000302:isolation & purification* / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D000097669:Dammaranes
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D016859:Lipoxygenase Inhibitors; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; D000097669:Dammaranes