Stearidonic acid, a plant-based dietary fatty acid, enhances the chemosensitivity of canine lymphoid tumor cells

Satyanarayana R Pondugula; Glennie Ferniany; Farah Ashraf; Kodye L Abbott; Bruce F Smith; Elaine S Coleman; Mahmoud Mansour; R Curtis Bird; Annette N Smith; Chandrabose Karthikeyan; Piyush Trivedi; Amit K Tiwari

doi:10.1016/j.bbrc.2015.03.141

Stearidonic acid, a plant-based dietary fatty acid, enhances the chemosensitivity of canine lymphoid tumor cells

Biochem Biophys Res Commun. 2015 May 15;460(4):1002-7. doi: 10.1016/j.bbrc.2015.03.141. Epub 2015 Apr 4.

Affiliations

¹ Department of Anatomy, Physiology and Pharmacology, Auburn University, Auburn, AL 36849, USA; Auburn University Research Initiative in Cancer, Auburn University, Auburn, AL 36849, USA. Electronic address: srp0010@auburn.edu.
² Department of Anatomy, Physiology and Pharmacology, Auburn University, Auburn, AL 36849, USA.
³ Department of Anatomy, Physiology and Pharmacology, Auburn University, Auburn, AL 36849, USA; Auburn University Research Initiative in Cancer, Auburn University, Auburn, AL 36849, USA.
⁴ Department of Pathobiology, Auburn University, Auburn, AL 36849, USA; Scott-Ritchey Research Center, Auburn University, Auburn, AL 36849, USA; Auburn University Research Initiative in Cancer, Auburn University, Auburn, AL 36849, USA.
⁵ Department of Pathobiology, Auburn University, Auburn, AL 36849, USA; Auburn University Research Initiative in Cancer, Auburn University, Auburn, AL 36849, USA.
⁶ Department of Clinical Sciences, Auburn University, Auburn, AL 36849, USA; Auburn University Research Initiative in Cancer, Auburn University, Auburn, AL 36849, USA.
⁷ School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Bhopal, MP 462033, India.
⁸ Department of Pharmacology and Experimental Therapeutics, The University of Toledo, Toledo, OH 43614, USA.

PMID: 25847597
DOI: 10.1016/j.bbrc.2015.03.141

Abstract

Lymphoma is the most common hematopoietic tumor in dogs and humans, with similar pathogenesis and therapeutic responses. Anticancer drugs like vincristine (VCR) and doxorubicin (DOX) are often used in treating lymphoma. However, the cure rate is generally poor due to chemoresistance. Here, we sought to determine whether stearidonic acid (SDA), a plant-based dietary fatty acid, sensitizes chemoresistant canine lymphoid-tumor cells. GL-1 B-cell lymphoid-tumor cells were found to be highly sensitive to the antitumor-activity of VCR and DOX, while OSW T-cell and 17-71 B-cell lymphoid-tumor cells were moderately and fully resistant, respectively. SDA, at its non-toxic concentrations, significantly promoted the antitumor action of VCR and DOX in both OSW and 17-71 cells. SDA-mediated chemosensitization was associated with SDA inhibition of P-glycoprotein (P-gp) function. This was confirmed in HEK293 cells stably expressing P-gp as well as by increased binding-affinity of SDA to P-gp in P-gp docking analysis. SDA at its chemosensitizing concentrations did not affect the viability of healthy dog peripheral blood mononuclear cells, suggesting that SDA is non-toxic to normal dog peripheral blood leucocytes at its chemosensitizing concentrations. Our study identifies a novel dietary fatty acid that may be used as a dietary supplement in combination with chemotherapy to promote the antitumor efficacy of the chemotherapy drugs in dogs and possibly in humans with chemoresistant lymphoma.

Keywords: Chemoresistance; Chemosensitization; Lymphoma; P-glycoprotein; Stearidonic acid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
Animals
Antineoplastic Agents / therapeutic use*
Cell Line, Tumor
Dogs
Drug Synergism
Fatty Acids, Omega-3 / pharmacology*
Fatty Acids, Omega-3 / therapeutic use
Lymphoma, B-Cell / drug therapy*
Plants / chemistry*

Substances

ATP Binding Cassette Transporter, Subfamily B, Member 1
Antineoplastic Agents
Fatty Acids, Omega-3
stearidonic acid