Anti-Cancer Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Michelle Prudhomme  
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France

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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

Author(s): 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.

Graphical Abstract:


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.

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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Article Details

VOLUME: 15
ISSUE: 8
Year: 2015
Page: [1066 - 1077]
Pages: 12
DOI: 10.2174/1871520615666150202110936
Price: $58