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Inhibition of Invasion in Pancreatic Cancer Cells by Conjugate of EPA with ?(3,3)-Pip-OH via PI3K/Akt/NF-kB Pathway.

ABSTRACT: The present work describes the anti-invasive effect of conjugate BC06, a novel conjugate of EPA, (2E,4E)-4-(benzo[d][1,3]dioxol-5-ylmethylene) hex-2-enoic acid with ?,?-disubstituted-?-amino acid, ?(3,3)-Pip-OH (2-(4-aminopiperidin-4-yl)acetic acid), in human pancreatic carcinoma. The conjugate BC06 inhibited invasion and migration of PANC-1 cells in wound healing, matrigel invasion, and gelatin degradation assays. Apart from suppressing PI3K/Akt/NF-kB signaling, which is involved in the up-regulation of matrix metalloproteinases, our study also demonstrated that dose-dependent treatment of BC06 results in the upregulation of TIMP-1 and E-cadherin expression. Further, BC06 was found to be inhibiting the metastatic ability of PANC-1 cells by reducing MMP-2 and MMP-9 expression. These findings suggest that EPA conjugate with ?(3,3)-Pip-OH, BC06, may be used as an anti-invasive agent against human pancreatic carcinoma.

SUBMITTER: Amin H 

PROVIDER: S-EPMC4601056 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Inhibition of Invasion in Pancreatic Cancer Cells by Conjugate of EPA with β(3,3)-Pip-OH via PI3K/Akt/NF-kB Pathway.

Amin Hina H   Wani Naiem Ahmad NA   Farooq Saleem S   Nayak Debasis D   Chakraborty Souneek S   Shankar Sudha S   Rasool Reyaz Ur RU   Koul Surinder S   Goswami Anindya A   Rai Rajkishor R  

ACS medicinal chemistry letters 20150831 10

The present work describes the anti-invasive effect of conjugate BC06, a novel conjugate of EPA, (2E,4E)-4-(benzo[d][1,3]dioxol-5-ylmethylene) hex-2-enoic acid with β,β-disubstituted-β-amino acid, β(3,3)-Pip-OH (2-(4-aminopiperidin-4-yl)acetic acid), in human pancreatic carcinoma. The conjugate BC06 inhibited invasion and migration of PANC-1 cells in wound healing, matrigel invasion, and gelatin degradation assays. Apart from suppressing PI3K/Akt/NF-kB signaling, which is involved in the up-regu  ...[more]

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