TY - JOUR
T1 - Luteolin and gemcitabine protect against pancreatic cancer in an orthotopic mouse model
AU - Johnson, Jodee L.
AU - Dia, Vermont P.
AU - Wallig, Matthew
AU - De Mejia, Elvira Gonzalez
N1 - Funding Information:
Dr Johnson was supported by US Department of Agriculture National Needs Graduate Fellowship Competitive grant number 2008-03560, National Institute of Food and Agriculture to the Division of Nutritional Sciences, and the University of Illinois. The research was supported by the Division of Nutritional Sciences, Vision 20/20 grant.
Funding Information:
From the *Division of Nutritional Sciences, †Department of Food Science and Human Nutrition, and ‡Department of Pathobiology, University of Illinois, Urbana-Champaign, Urbana, IL. Received for publication October 28, 2013; accepted June 30, 2014. Reprints: Elvira Gonzalez de Mejia, PhD, 228 ERML, MC-051, 1201 W. Gregory Dr, Urbana, IL 61801 (e‐mail: edemejia@illinois.edu). This study was supported by University of Illinois, Division of Nutritional Sciences, Vision 20/20 grant. The authors declare no conflict of interest. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Website (www.pancreasjournal.com). Copyright © 2014 by Lippincott Williams & Wilkins
Funding Information:
Dr Johnson was supported by US Department of Agriculture National Needs Graduate Fellowship Competitive grant number 2008–03560, National Institute of Food and Agriculture to the Division of Nutritional Sciences, and the University of Illinois. The research was supported by the Division of Nutritional Sciences, Vision 20/20 grant. The authors thank Stephanie Andler, Julia Amador, Guadalupe Garcia, Michelle Johnson, and Valerie Munoz for their technical assistance.
Publisher Copyright:
Copyright © 2014 by Lippincott Williams & Wilkins.
PY - 2015/1
Y1 - 2015/1
N2 - Objective: This study aimed to evaluate the ability of luteolin (Lut), gemcitabine (Gem), and their combination (Lut + Gem) to prevent the growth of pancreatic tumors in vivo. Methods: The antitumor effect of intraperitoneally administered Lut, Gem, and Lut + Gem was evaluated using an orthotopic mouse model for 6 weeks. Tumor growth after injection of human pancreatic cancer cells was assessed by measuring pancreatic tumor mass. The mechanism of action of antitumor effect was assessed by immunohistochemistry and Western blot procedures. Results: Luteolin + Gem significantly lowered (P = 0.048) the pancreatic tumor mass compared with control. Luteolin, Gem, and Lut + Gem significantly reduced the proliferating cell nuclear antigen expression (25%, 37%, and 37%, respectively). Luteolin + Gemtreatment led to a significant reduction in the expressions of K-ras (46%, P = 0.0006), GSK-3β (34%, P = 0.014), P(Tyr216)GSK-3β (16%, P = 0.033), P(Ser311)NF-κB p65 (27%, P = 0.036), and bcl-2/bax ratio (68%, P = 0.006) while significantly increasing the expressions of cytochrome c (44%, P = 0.035) and caspase 3 (417%, P = 0.003). Conclusions: Luteolin + Gem promoted apoptotic cell death in pancreatic tumor cells in vivo through inhibition of the K-ras/GSK-3β/NF-κB signaling pathway, leading to a reduction in the Bcl-2/Bax ratio, release of cytochrome c, and activation of caspase 3.
AB - Objective: This study aimed to evaluate the ability of luteolin (Lut), gemcitabine (Gem), and their combination (Lut + Gem) to prevent the growth of pancreatic tumors in vivo. Methods: The antitumor effect of intraperitoneally administered Lut, Gem, and Lut + Gem was evaluated using an orthotopic mouse model for 6 weeks. Tumor growth after injection of human pancreatic cancer cells was assessed by measuring pancreatic tumor mass. The mechanism of action of antitumor effect was assessed by immunohistochemistry and Western blot procedures. Results: Luteolin + Gem significantly lowered (P = 0.048) the pancreatic tumor mass compared with control. Luteolin, Gem, and Lut + Gem significantly reduced the proliferating cell nuclear antigen expression (25%, 37%, and 37%, respectively). Luteolin + Gemtreatment led to a significant reduction in the expressions of K-ras (46%, P = 0.0006), GSK-3β (34%, P = 0.014), P(Tyr216)GSK-3β (16%, P = 0.033), P(Ser311)NF-κB p65 (27%, P = 0.036), and bcl-2/bax ratio (68%, P = 0.006) while significantly increasing the expressions of cytochrome c (44%, P = 0.035) and caspase 3 (417%, P = 0.003). Conclusions: Luteolin + Gem promoted apoptotic cell death in pancreatic tumor cells in vivo through inhibition of the K-ras/GSK-3β/NF-κB signaling pathway, leading to a reduction in the Bcl-2/Bax ratio, release of cytochrome c, and activation of caspase 3.
KW - Apoptosis
KW - GSK-3β
KW - Gemcitabine
KW - Luteolin
KW - NF-κB
KW - Pancreatic cancer
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U2 - 10.1097/MPA.0000000000000215
DO - 10.1097/MPA.0000000000000215
M3 - Article
C2 - 25237909
AN - SCOPUS:84913554641
VL - 44
SP - 144
EP - 151
JO - Pancreas
JF - Pancreas
SN - 0885-3177
IS - 1
ER -