title: Stearidonic acid, a plant-based dietary fatty acid, enhances the chemosensitivity of canine lymphoid tumor cells.
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.
authors.affiliation: 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.
authors.forename: Satyanarayana R
authors.initials: SR
authors.lastname: Pondugula
authors.affiliation: Department of Anatomy, Physiology and Pharmacology, Auburn University, Auburn, AL 36849, USA.
authors.forename: Glennie
authors.initials: G
authors.lastname: Ferniany
authors.affiliation: Department of Anatomy, Physiology and Pharmacology, Auburn University, Auburn, AL 36849, USA.
authors.forename: Farah
authors.initials: F
authors.lastname: Ashraf
authors.affiliation: Department of Anatomy, Physiology and Pharmacology, Auburn University, Auburn, AL 36849, USA; Auburn University Research Initiative in Cancer, Auburn University, Auburn, AL 36849, USA.
authors.forename: Kodye L
authors.initials: KL
authors.lastname: Abbott
authors.affiliation: 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.
authors.forename: Bruce F
authors.initials: BF
authors.lastname: Smith
authors.affiliation: Department of Anatomy, Physiology and Pharmacology, Auburn University, Auburn, AL 36849, USA.
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Coleman
authors.affiliation: Department of Anatomy, Physiology and Pharmacology, Auburn University, Auburn, AL 36849, USA; Auburn University Research Initiative in Cancer, Auburn University, Auburn, AL 36849, USA.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Mansour
authors.affiliation: Department of Pathobiology, Auburn University, Auburn, AL 36849, USA; Auburn University Research Initiative in Cancer, Auburn University, Auburn, AL 36849, USA.
authors.forename: R Curtis
authors.initials: RC
authors.lastname: Bird
authors.affiliation: Department of Clinical Sciences, Auburn University, Auburn, AL 36849, USA; Auburn University Research Initiative in Cancer, Auburn University, Auburn, AL 36849, USA.
authors.forename: Annette N
authors.initials: AN
authors.lastname: Smith
authors.affiliation: School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Bhopal, MP 462033, India.
authors.forename: Chandrabose
authors.initials: C
authors.lastname: Karthikeyan
authors.affiliation: School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Bhopal, MP 462033, India.
authors.forename: Piyush
authors.initials: P
authors.lastname: Trivedi
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, The University of Toledo, Toledo, OH 43614, USA.
authors.forename: Amit K
authors.initials: AK
authors.lastname: Tiwari
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004285:Dogs; D004357:Drug Synergism; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology* / Q000627:therapeutic use; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D010944:Plants / Q000737:chemistry*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D015525:Fatty Acids, Omega-3; C062895:stearidonic acid
keywords: Chemoresistance; Chemosensitization; Lymphoma; P-glycoprotein; Stearidonic acid