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Urbana, IL, United States

Johnson J.L.,228 ERML | Wallig M.,University of Illinois at Urbana - Champaign | De Mejia E.G.,228 ERML
Pancreas | Year: 2015

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. © 2014 Lippincott Williams & Wilkins. Source

The effect of lunasin on colon cancer metastasis was studied using three human colon cancer cell lines in vitro and a liver metastasis model of colon cancer in vivo. Lunasin bound with α 5β 1 integrin and internalized into the nucleus of KM12L4 human colon cancer cells. Lunasin (10μM) inhibited the activation of focal adhesion kinase (FAK) by 28%, 39% and 60% in RKO, HCT-116 and KM12L4 human colon cancer cells, respectively. Lunasin caused an increase in the expression of the inhibitor of kappa B alpha (IκB-α), a decrease in nuclear p50 NF-κB and a reduction in the migration of cancer cells. Lunasin (4mg/kg bw) inhibited metastasis and potentiated the effect of oxaliplatin by reducing the expression of proliferating cell nuclear antigen. Liver metastatic nodules were reduced from 28 (PBS) to 14 (lunasin, P=0.047) while combination of lunasin and oxaliplatin to 5 (P=0.004). The tumor burden was reduced from 0.13 (PBS) to 0.10 (lunasin, P=0.039) to 0.04 (lunasin+oxaliplatin, P<0.0001). Moreover, lunasin potentiated the effect of oxaliplatin in modifying expression of proteins involved in apoptosis and metastasis including Bax, Bcl-2, IKK-α and p-p65. Lunasin inhibited metastasis of human colon cancer cells by direct binding with α 5β 1 integrin suppressing FAK/ERK/NF-κB signaling, and potentiated the effect of oxaliplatin in preventing the outgrowth of metastasis. © 2011 Elsevier Ireland Ltd. Source

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