DOX-Vit D, a Novel Doxorubicin Delivery Approach, Inhibits Human Osteosarcoma Cell Proliferation by Inducing Apoptosis While Inhibiting Akt and mTOR Signaling Pathways
Doxorubicin (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 b...
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| Format: | Article |
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MDPI AG
2018-09-01
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| Series: | Pharmaceutics |
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| Online Access: | http://www.mdpi.com/1999-4923/10/3/144 |
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| author | Zaid H. Maayah Ti Zhang Marcus Laird Forrest Samaa Alrushaid Michael R. Doschak Neal M. Davies Ayman O. S. El-Kadi |
| author_facet | Zaid H. Maayah Ti Zhang Marcus Laird Forrest Samaa Alrushaid Michael R. Doschak Neal M. Davies Ayman O. S. El-Kadi |
| author_sort | Zaid H. Maayah |
| collection | DOAJ |
| description | Doxorubicin (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. |
| first_indexed | 2024-04-11T20:52:09Z |
| format | Article |
| id | doaj.art-b0bc14d25cf445ab82630af70338b5bd |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T20:52:09Z |
| publishDate | 2018-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-b0bc14d25cf445ab82630af70338b5bd2022-12-22T04:03:49ZengMDPI AGPharmaceutics1999-49232018-09-0110314410.3390/pharmaceutics10030144pharmaceutics10030144DOX-Vit D, a Novel Doxorubicin Delivery Approach, Inhibits Human Osteosarcoma Cell Proliferation by Inducing Apoptosis While Inhibiting Akt and mTOR Signaling PathwaysZaid H. Maayah0Ti Zhang1Marcus Laird Forrest2Samaa Alrushaid3Michael R. Doschak4Neal M. Davies5Ayman O. S. El-Kadi6Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2E1, CanadaDepartment of Pharmaceutical Chemistry, School of Pharmacy, University of Kansas, Lawrence, KS 66047, USADepartment of Pharmaceutical Chemistry, School of Pharmacy, University of Kansas, Lawrence, KS 66047, USADepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Kuwait University, Safat 13110, KuwaitFaculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2E1, CanadaFaculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2E1, CanadaFaculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2E1, CanadaDoxorubicin (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.http://www.mdpi.com/1999-4923/10/3/144doxorubicinMG63Vitamin DDOX-Vit D |
| spellingShingle | Zaid H. Maayah Ti Zhang Marcus Laird Forrest Samaa Alrushaid Michael R. Doschak Neal M. Davies Ayman O. S. El-Kadi DOX-Vit D, a Novel Doxorubicin Delivery Approach, Inhibits Human Osteosarcoma Cell Proliferation by Inducing Apoptosis While Inhibiting Akt and mTOR Signaling Pathways Pharmaceutics doxorubicin MG63 Vitamin D DOX-Vit D |
| title | DOX-Vit D, a Novel Doxorubicin Delivery Approach, Inhibits Human Osteosarcoma Cell Proliferation by Inducing Apoptosis While Inhibiting Akt and mTOR Signaling Pathways |
| title_full | DOX-Vit D, a Novel Doxorubicin Delivery Approach, Inhibits Human Osteosarcoma Cell Proliferation by Inducing Apoptosis While Inhibiting Akt and mTOR Signaling Pathways |
| title_fullStr | DOX-Vit D, a Novel Doxorubicin Delivery Approach, Inhibits Human Osteosarcoma Cell Proliferation by Inducing Apoptosis While Inhibiting Akt and mTOR Signaling Pathways |
| title_full_unstemmed | DOX-Vit D, a Novel Doxorubicin Delivery Approach, Inhibits Human Osteosarcoma Cell Proliferation by Inducing Apoptosis While Inhibiting Akt and mTOR Signaling Pathways |
| title_short | DOX-Vit D, a Novel Doxorubicin Delivery Approach, Inhibits Human Osteosarcoma Cell Proliferation by Inducing Apoptosis While Inhibiting Akt and mTOR Signaling Pathways |
| title_sort | dox vit d a novel doxorubicin delivery approach inhibits human osteosarcoma cell proliferation by inducing apoptosis while inhibiting akt and mtor signaling pathways |
| topic | doxorubicin MG63 Vitamin D DOX-Vit D |
| url | http://www.mdpi.com/1999-4923/10/3/144 |
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