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.
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Authors | Nagendra Sastry Yarla, Rajaram Azad, Mahaboob Basha, Abdul Rajack, D S V G K Kaladhar, Bharat Kumar Allam, Rajeswara Rao Pragada, Krishna Nand Singh, Sunanda Kumari K, Reddanna Pallu, Umadevi Parimi, Anupam Bishayee, Govinda Rao Duddukuri |
Journal | Anti-cancer agents in medicinal chemistry
(Anticancer Agents Med Chem)
Vol. 15
Issue 8
Pg. 1066-77
( 2015)
ISSN: 1875-5992 [Electronic] Netherlands |
PMID | 25642980
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Cyclooxygenase Inhibitors
- Lipopolysaccharides
- Lipoxygenase Inhibitors
- Triterpenes
- Tumor Necrosis Factor-alpha
- dammarane
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Topics |
- Animals
- Anti-Inflammatory Agents
(isolation & purification, pharmacology)
- Antineoplastic Agents
(isolation & purification, pharmacology)
- Apoptosis
(drug effects)
- Arecaceae
(chemistry)
- Caco-2 Cells
- Cell Line, Tumor
- Cyclooxygenase Inhibitors
(isolation & purification, pharmacology)
- Down-Regulation
(drug effects)
- Edema
(chemically induced, immunology, pathology)
- HL-60 Cells
- Humans
- Lipopolysaccharides
- Lipoxygenase Inhibitors
(isolation & purification, pharmacology)
- Male
- Monocytes
(drug effects, immunology, metabolism)
- Pancreatic Neoplasms
(immunology, metabolism, pathology)
- Rats
- Rats, Wistar
- Seeds
(chemistry)
- Triterpenes
(isolation & purification, pharmacology)
- Tumor Necrosis Factor-alpha
(metabolism)
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