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Induction of apoptosis and nonsteroidal anti‐inflammatory drug‐activated gene 1 in pancreatic cancer cells by a glycyrrhetinic acid derivative
Author(s) -
Jutooru Indira,
Chadalapaka Gayathri,
Chintharlapalli Sudhakar,
Papineni Sabitha,
Safe Stephen
Publication year - 2009
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20518
Subject(s) - biology , transactivation , mapk/erk pathway , p38 mitogen activated protein kinases , cancer research , cancer cell , microbiology and biotechnology , protein kinase a , kinase , transcription factor , biochemistry , cancer , gene , genetics
Methyl 2‐cyano‐3,11‐dioxo‐18β‐olean‐1,12‐dien‐30‐oate (CDODA‐Me) is a synthetic triterpenoid derived from glycyrrhetinic acid, a bioactive phytochemical in licorice, CDODA‐Me inhibits growth of Panc1 and Panc28 pancreatic cancer cell lines and activates peroxisome proliferator‐activated receptor γ (PPARγ)‐dependent transactivation in these cells. CDODA‐Me also induced p21 and p27 protein expression and downregulates cyclin D1; however, these responses were receptor‐independent. CDODA‐Me induced apoptosis in Panc1 and Panc28 cells, and this was accompanied by receptor‐independent induction of the proapoptotic proteins early growth response‐1 (Egr‐1), nonsteroidal anti‐inflammatory drug‐activated gene‐1 (NAG‐1), and activating transcription factor‐3 (ATF3). Induction of NAG‐1 and Egr‐1 by CDODA‐Me was dependent on activation of phosphatidylinositol‐3‐kinase (PI3‐K) and/or p42 and p38 mitogen‐activated protein kinase (MAPK) pathways but there were differences between Panc28 and Panc1 cells. Induction of NAG‐1 in Panc28 cells was p38‐MAPK‐ and PI3‐K‐dependent but Egr‐1‐independent, whereas induction in Panc1 cells was associated with activation of p38‐MAPK, PI3‐K, and p42‐MAPK and was only partially Egr‐1‐dependent. This is the first report of the induction of the proapoptotic protein NAG‐1 in pancreatic cancer cells. © 2009 Wiley‐Liss, Inc.