Inhibition of Invasion in Pancreatic Cancer Cells by Conjugate of EPA with β(3,3)-Pip-OH via PI3K/Akt/NF-kB Pathway.
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-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 β(3,3)-Pip-OH, BC06, may be used as an anti-invasive agent against human pancreatic carcinoma.
Cancer Pharmacology Division, Medicinal Chemistry Division, and Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine , Canal Road, Jammu Tawi, J&K 180001, India.
Hina
H
Amin
Cancer Pharmacology Division, Medicinal Chemistry Division, and Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine , Canal Road, Jammu Tawi, J&K 180001, India.
Naiem Ahmad
NA
Wani
Cancer Pharmacology Division, Medicinal Chemistry Division, and Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine , Canal Road, Jammu Tawi, J&K 180001, India.
Saleem
S
Farooq
Cancer Pharmacology Division, Medicinal Chemistry Division, and Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine , Canal Road, Jammu Tawi, J&K 180001, India.
Debasis
D
Nayak
Cancer Pharmacology Division, Medicinal Chemistry Division, and Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine , Canal Road, Jammu Tawi, J&K 180001, India.
Souneek
S
Chakraborty
Cancer Pharmacology Division, Medicinal Chemistry Division, and Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine , Canal Road, Jammu Tawi, J&K 180001, India.
Sudha
S
Shankar
Cancer Pharmacology Division, Medicinal Chemistry Division, and Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine , Canal Road, Jammu Tawi, J&K 180001, India.
Reyaz Ur
RU
Rasool
Cancer Pharmacology Division, Medicinal Chemistry Division, and Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine , Canal Road, Jammu Tawi, J&K 180001, India.
Surinder
S
Koul
Cancer Pharmacology Division, Medicinal Chemistry Division, and Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine , Canal Road, Jammu Tawi, J&K 180001, India.
Anindya
A
Goswami
Cancer Pharmacology Division, Medicinal Chemistry Division, and Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine , Canal Road, Jammu Tawi, J&K 180001, India.
Rajkishor
R
Rai
AKT; invasion; metastasis; piperic acid; β,β-disubstituted-β-amino acid