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dc.contributor.authorMaayah, Zaid H.
dc.contributor.authorZhang, Ti
dc.contributor.authorForrest, Marcus Laird
dc.contributor.authorAlrushaid, Samaa
dc.contributor.authorDoschak, Michael R.
dc.contributor.authorDavies, Neal M.
dc.contributor.authorEl-Kadi, Ayman O. S.
dc.date.accessioned2020-12-02T15:55:08Z
dc.date.available2020-12-02T15:55:08Z
dc.date.issued2018-09-04
dc.identifier.citationMaayah, Z. H., Zhang, T., Forrest, M. L., Alrushaid, S., Doschak, M. R., Davies, N. M., & El-Kadi, A. (2018). DOX-Vit D, a Novel Doxorubicin Delivery Approach, Inhibits Human Osteosarcoma Cell Proliferation by Inducing Apoptosis While Inhibiting Akt and mTOR Signaling Pathways. Pharmaceutics, 10(3), 144. https://doi.org/10.3390/pharmaceutics10030144en_US
dc.identifier.urihttp://hdl.handle.net/1808/30954
dc.descriptionThis work is licensed under a Creative Commons Attribution 4.0 International License.en_US
dc.description.abstractDoxorubicin (DOX) is a very potent and effective anticancer agent. However, the effectiveness of DOX in osteosarcoma is usually limited by the acquired drug resistance. Recently, Vitamin D (Vit-D) was shown to suppress the growth of many human cancer cells. Taken together, we synthesized DOX-Vit D by conjugating Vit-D to DOX in order to increase the delivery of DOX into cancer cells and mitigate the chemoresistance associated with DOX. For this purpose, MG63 cells were treated with 10 µM DOX or DOX-Vit D for 24 h. Thereafter, MTT, real-time PCR and western blot analysis were used to determine cell proliferation, genes and proteins expression, respectively. Our results showed that DOX-Vit D, but not DOX, significantly elicited an apoptotic signal in MG63 cells as evidenced by induction of death receptor, Caspase-3 and BCLxs genes. Mechanistically, the DOX-Vit D-induced apoptogens were credited to the activation of p-JNK and p-p38 signaling pathway and the inhibition of proliferative proteins, p-Akt and p-mTOR. Our findings propose that DOX-Vit D suppressed the growth of MG63 cells by inducing apoptosis while inhibiting cell survival and proliferative signaling pathways. DOX-Vit D may serve as a novel drug delivery approach to potentiate the delivery of DOX into cancer cells.en_US
dc.description.sponsorshipCanadian Institutes of Health Research [Grant 106665]en_US
dc.description.sponsorshipU.S. National Cancer Institute [Grant R01CA173292]en_US
dc.publisherMDPIen_US
dc.rights© 2018 by the authors. Licensee MDPI, Basel, Switzerland.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectDoxorubicinen_US
dc.subjectMG63en_US
dc.subjectVitamin Den_US
dc.subjectDOX-Vit Den_US
dc.titleDOX-Vit D, a Novel Doxorubicin Delivery Approach, Inhibits Human Osteosarcoma Cell Proliferation by Inducing Apoptosis While Inhibiting Akt and mTOR Signaling Pathwaysen_US
dc.typeArticleen_US
kusw.kuauthorZhang, Ti
kusw.kuauthorForrest, Marcus Laird
kusw.kudepartmentPharmaceutical Chemistryen_US
dc.identifier.doi10.3390/pharmaceutics10030144en_US
dc.identifier.orcidhttps://orcid.org/0000-0001-7705-9025en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-0293-6596en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-7050-1471en_US
kusw.oaversionScholarly/refereed, publisher versionen_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.identifier.pmidPMC6161239en_US
dc.rights.accessrightsopenAccessen_US


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© 2018 by the authors. Licensee MDPI, Basel, Switzerland.
Except where otherwise noted, this item's license is described as: © 2018 by the authors. Licensee MDPI, Basel, Switzerland.