Phloridzin docosahexaenoate, a novel polyphenolic derivative, is cytotoxic to canine osteosarcoma D17 cells
Main Article Content
Abstract
Canine osteosarcoma (OSA) is the most common form of bone cancer diagnosticated in dogs and is highly metastatic. There has been limited advancement in discovering an effective treatment for OSA in the last few decades. The major drawback of the currently used chemotherapeutic drugs is their side effects. In this preliminary study, we investigated the efficacy of using a novel food-derived drug, phloridzin docosahexaenoate (PZ-DHA), in the treatment of canine OSA in vitro. PZ-DHA was selectively cytotoxic to canine OSA D17 cells, while normal human liver cells (WRL68) were more resistant. We also found that PZ-DHA had enhanced cellular uptake in D17 cells compared to its precursors and in WRL68 cell line. This study provides preliminary evidence that PZ-DHA needs to be further assessed as a safe and efficacious new drug in the treatment of both canine and human OSA.
Keywords:
Phloridzin, docosahexaenoic acid, cancer, cytotoxicity, cellular uptake, dog
Article Details
How to Cite
MURRAY, Beth et al.
Phloridzin docosahexaenoate, a novel polyphenolic derivative, is cytotoxic to canine osteosarcoma D17 cells.
Medical Research Archives, [S.l.], v. 9, n. 5, may 2021.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2438>. Date accessed: 26 dec. 2024.
doi: https://doi.org/10.18103/mra.v9i5.2438.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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3. Fernando W, Coombs MRP, Hoskin DW, Rupasinghe HPV. Docosahexaenoic acid-acylated phloridzin, a novel polyphenol fatty acid ester derivative, is cytotoxic to breast cancer cells. 2016. Carcinog. 37, 1004–1013.
4. Fernando W, Coyle K, Marcato P, Rupasinghe HPV, Hoskin DW. Phloridzin docosahexaenoate, a novel fatty acid ester of a plant polyphenol, inhibits mammary carcinoma cell metastasis. 2019. Cancer Lett. 465, 68–81.
5. Fernando W, Goralski KB, Hoskin DW, Rupasinghe HPV. Metabolism and pharmacokinetics of a novel polyphenol fatty acid ester phloridzin docosahexaenoate in Balb/c female mice. 2020. Sci. Reports, 10, 1-12.
6. Gee JM, DuPont MS, Day AJ, Plumb GW, Williamson G, Johnson IT. transport of quercetin glycosides in rats involves both deglycosylation and interaction with the hexose transport pathway. 2000. J. Nutr. 130, 2765–2771.
7. Hishikawa D, Valentine WJ, Iizuka‐Hishikawa Y, Shindou H, Shimizu T. Metabolism and functions of docosahexaenoic acid-containing membrane glycerophospholipids. 2017. FEBS Lett. 591, 2730–2744.
8. Mantso T, Trafalis DT, Botaitis S, Franco R, Pappa A, Rupasinghe HPV, Panayiotidis MI. Novel docosahexaenoic acid ester of phloridzin inhibits proliferation and triggers apoptosis in an in vitro model of skin cancer. 2018. Antioxid. 7, 188.
9. Martin RE, Wickham JQ, Om AS, Sanders J, Ceballos N. Uptake and incorporation of docosahexaenoic acid (DHA) into neuronal cell body and neurite/nerve growth cone lipids: evidence of compartmental DHA metabolism in nerve growth factor-differentiated PC12 cells. 2000. Neurochem. Res. 25, 715–723.
10. Montgomery DC. Design and analysis of experiments, tenth ed. Wiley, New York.
11. Morello, E., Martano, M., Buracco, P. 2011. Biology, diagnosis and treatment of canine appendicular osteosarcoma: similarities and differences with human osteosarcoma. 2020. Vet. J. 189, 268-277.
12. Nair SVG, Ziaullah, Rupasinghe HPV. Fatty acid esters of phloridzin induce apoptosis of human liver cancer cells through altered gene expression. 2014. PLoS One. 9, e107149.
13. Newell M, Baker K, Postovit LM, Field CJ. A critical review on the effect of docosahexaenoic acid (DHA) on cancer cell cycle progression. 2017. Int. J. Mol. Sci. 18, 1784.
14. Sak K. Cytotoxicity of dietary flavonoids on different human cancer types. 2014. Pharmacogn. Rev. 8, 122–146.
15. Sánchez-Céspedes R, Accornero P, Miretti S, Martignani E, Gattino F, Maniscalco L, Gola C, Iussich S, Martano M, Morello E, Buracco P, Aresu L, Maria R. In vitro and in vivo effects of toceranib phosphate on canine osteosarcoma cell lines and xenograft orthotopic models. 2020. Vet Comp Oncol. 18, 117-127.
16. SAS Institute Inc, 2014. SAS/STAT 9.4 user’s guide. SAS Institute Inc. Cary, North Carolina.
17. Selmic LE, Burton JH, Thamm DH, Withrow SJ, Lana SE. Comparison of carboplatin and doxorubicin-based chemotherapy protocols in 470 dogs after amputation for treatment of appendicular osteosarcoma. 2014. J. Vet. Intern. Med. 28, 554–563.
18. Straw RC, Withrow SJ, Richter SL, Powers BE, Klein MK, Postorino NC, LaRue SM, Ogilvie GK, Vail DM, Morrison WB, McGee M, Dickinson K. Amputation and cisplatin for treatment of canine osteosarcoma. 1991. J. Vet. Intern. Med. 5, 205–210.
19. Szewczyk M, Lechowski R, Zabielska K. What do we know about canine osteosarcoma treatment? – Review. 2015. Vet. Res. Commun. 39, 61–67.
20. Wu CH, Ho YS, Tsai CY, Wang YJ, Tseng H, Wei PL, Lee CH, Liu RS, Lin SY. In vitro and in vivo study of phloretin-induced apoptosis in human liver cancer cells involving inhibition of type II glucose transporter. 2009. Int. J. Cancer. 124, 2210–2219.
21. Zhong Y, Shahidi F. Lipophilized epigallocatechin gallate (EGCG) derivatives as novel antioxidants. 2011. J. Agric. Food Chem. 59, 6526–6533.
22. Ziaullah, Bhullar KS, Warnakulasuriya SN, Rupasinghe HPV. Biocatalytic synthesis, structural elucidation, antioxidant capacity and tyrosinase inhibition activity of long chain fatty acid acylated derivatives of phloridzin and isoquercitrin. 2013.Bioorg. Med. Chem. 21, 684–692.