Title:Chia Seeds Oil Suppresses the Resistance of Hepatocellular Carcinoma
Cells to Liposomal-doxorubicin and Upregulates the Tumor Suppressor
miRNAs
Volume: 24
Issue: 4
Author(s): Shaimaa A. Tawfik, Els T. Awad*, Hoda O. Abu Bakr, Ismail M. Ahmed, Esmat Ashour and Amira M. Gamal-Eldeen
Affiliation:
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Cairo
University, Cairo, Egypt
Keywords:
Chia seed oil, resistance to liposomal-doxorubicin, HCC, tumor-suppressing miRNAs, CYP-3A4, MRP1.
Abstract:
Background: Chia seed is an oil seed with multiple biological activities. Doxorubicin is
effective chemotherapy for liver cancer. Resistance and adverse effects are doxorubicin limitations.
Objective: This study aimed to investigate the effect of chia seeds oil (CSO) on the resistance of
HepG2 cells to liposomal-doxorubicin (DOX).
Methods: The objective were investigated through measuring cytotoxicity, doxorubicin-metabolizing
enzyme Cytochrome P450 3A4 (CYP-3A4), multidrug resistance-associated protein (MRP1), and the
expression of multiple tumor suppressor microRNAs.
Results: The findings indicated that low concentration of CSO increased HepG2 cells' sensitivity to
DOX, as concluded from its higher cytotoxicity. DOX-induced mRNAs of CYP-3A4 and MRP1 and
their protein levels. CSO inhibited both in DOX-treated cells. CSO-induced tumor suppressor miRNAs.
Doxorubicin inhibited miR-122 and let-7/b/e expression, while it led to overexpression of let-
7a. CSO/DOX upregulated let-7/b/e, miR-34a, and miR-122 (which inhibits MRP1) and downregulated
let-7a, which may lead to increased apoptosis.
Conclusion: CSO effectively re-sensitized HepG2 cells to liposomal-doxorubicin via inhibiting
MRP1 and CYP-3A4, which may increase in vivo doxorubicin bioavailability and decrease its therapeutic
dose to diminish its adverse effects.