Optimized Conjugation of Fluvastatin to HIV-1 TAT Displays Enhanced Pro-Apoptotic Activity in HepG2 Cells
Accumulating evidence indicates that statins reduce the risk of different cancers and inhibit the proliferation of liver cancer cells. This study aims to explore whether the electrostatic conjugation of optimized fluvastatin (FLV) to human immunodeficiency virus type 1 (HIV-1) trans-activator transc...
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MDPI AG
2020-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/11/4138 |
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| author | Lamya H. Al-Wahaibi Muneera S. M. Al-Saleem Osama A. A. Ahmed Usama A. Fahmy Nabil A. Alhakamy Basma G. Eid Ashraf B. Abdel-Naim Wael M. Abdel-Mageed Maha M. AlRasheed Gamal A. Shazly |
| author_facet | Lamya H. Al-Wahaibi Muneera S. M. Al-Saleem Osama A. A. Ahmed Usama A. Fahmy Nabil A. Alhakamy Basma G. Eid Ashraf B. Abdel-Naim Wael M. Abdel-Mageed Maha M. AlRasheed Gamal A. Shazly |
| author_sort | Lamya H. Al-Wahaibi |
| collection | DOAJ |
| description | Accumulating evidence indicates that statins reduce the risk of different cancers and inhibit the proliferation of liver cancer cells. This study aims to explore whether the electrostatic conjugation of optimized fluvastatin (FLV) to human immunodeficiency virus type 1 (HIV-1) trans-activator transcription peptide (TAT) would enhance the anti-proliferative activity against HepG2 cells. FLV–TAT conjugation was optimized to achieve the lowest size with highest zeta potential. Nine formulae were constructed, using a factorial design with three factors—FLV concentration, TAT concentration, and pH of the medium—while the responses were zeta potential and size. The optimized formula showed a particle size of 199.24 nm and 29.14 mV zeta potential. Data indicates that conjugation of FLV to TAT (optimized formula) significantly enhances anti-proliferative activity and uptake by HepG2 cells when compared to raw FLV. Flow cytometry showed significant accumulation of cells in the pre-G phase, which highlights higher apoptotic activity. Annexin V staining indicated a significant increase in total cell death in early and late apoptosis. This was confirmed by significantly elevated caspase 3 in cells exposed to FLV–TAT preparation. In conclusion, the FLV–TAT optimized formula exhibited improved anti-proliferative action against HepG2. This is partially attributed to the enhanced apoptotic effects and cellular uptake of FLV. |
| first_indexed | 2024-03-10T19:16:10Z |
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| language | English |
| last_indexed | 2024-03-10T19:16:10Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-932f4b3cfe684e24a1c7e948f4d7a4012023-11-20T03:25:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-012111413810.3390/ijms21114138Optimized Conjugation of Fluvastatin to HIV-1 TAT Displays Enhanced Pro-Apoptotic Activity in HepG2 CellsLamya H. Al-Wahaibi0Muneera S. M. Al-Saleem1Osama A. A. Ahmed2Usama A. Fahmy3Nabil A. Alhakamy4Basma G. Eid5Ashraf B. Abdel-Naim6Wael M. Abdel-Mageed7Maha M. AlRasheed8Gamal A. Shazly9Department of Chemistry, Science College, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi ArabiaDepartment of Chemistry, Science College, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaDepartment of Clinical Pharmacy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaAccumulating evidence indicates that statins reduce the risk of different cancers and inhibit the proliferation of liver cancer cells. This study aims to explore whether the electrostatic conjugation of optimized fluvastatin (FLV) to human immunodeficiency virus type 1 (HIV-1) trans-activator transcription peptide (TAT) would enhance the anti-proliferative activity against HepG2 cells. FLV–TAT conjugation was optimized to achieve the lowest size with highest zeta potential. Nine formulae were constructed, using a factorial design with three factors—FLV concentration, TAT concentration, and pH of the medium—while the responses were zeta potential and size. The optimized formula showed a particle size of 199.24 nm and 29.14 mV zeta potential. Data indicates that conjugation of FLV to TAT (optimized formula) significantly enhances anti-proliferative activity and uptake by HepG2 cells when compared to raw FLV. Flow cytometry showed significant accumulation of cells in the pre-G phase, which highlights higher apoptotic activity. Annexin V staining indicated a significant increase in total cell death in early and late apoptosis. This was confirmed by significantly elevated caspase 3 in cells exposed to FLV–TAT preparation. In conclusion, the FLV–TAT optimized formula exhibited improved anti-proliferative action against HepG2. This is partially attributed to the enhanced apoptotic effects and cellular uptake of FLV.https://www.mdpi.com/1422-0067/21/11/4138fluvastatinHIV-TATHepG2 cellsapoptosiscationic peptidecancer |
| spellingShingle | Lamya H. Al-Wahaibi Muneera S. M. Al-Saleem Osama A. A. Ahmed Usama A. Fahmy Nabil A. Alhakamy Basma G. Eid Ashraf B. Abdel-Naim Wael M. Abdel-Mageed Maha M. AlRasheed Gamal A. Shazly Optimized Conjugation of Fluvastatin to HIV-1 TAT Displays Enhanced Pro-Apoptotic Activity in HepG2 Cells International Journal of Molecular Sciences fluvastatin HIV-TAT HepG2 cells apoptosis cationic peptide cancer |
| title | Optimized Conjugation of Fluvastatin to HIV-1 TAT Displays Enhanced Pro-Apoptotic Activity in HepG2 Cells |
| title_full | Optimized Conjugation of Fluvastatin to HIV-1 TAT Displays Enhanced Pro-Apoptotic Activity in HepG2 Cells |
| title_fullStr | Optimized Conjugation of Fluvastatin to HIV-1 TAT Displays Enhanced Pro-Apoptotic Activity in HepG2 Cells |
| title_full_unstemmed | Optimized Conjugation of Fluvastatin to HIV-1 TAT Displays Enhanced Pro-Apoptotic Activity in HepG2 Cells |
| title_short | Optimized Conjugation of Fluvastatin to HIV-1 TAT Displays Enhanced Pro-Apoptotic Activity in HepG2 Cells |
| title_sort | optimized conjugation of fluvastatin to hiv 1 tat displays enhanced pro apoptotic activity in hepg2 cells |
| topic | fluvastatin HIV-TAT HepG2 cells apoptosis cationic peptide cancer |
| url | https://www.mdpi.com/1422-0067/21/11/4138 |
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