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Awan ZA, Fahmy UA, Badr-Eldin SM, et al. The Enhanced Cytotoxic and Pro-Apoptotic Effects of Optimized Simvastatin-Loaded Emulsomes on MCF-7 Breast Cancer Cells. Pharmaceutics. 2020;12(7)doi: 10.3390/pharmaceutics12070597.
Awan, Z. A., Fahmy, U. A., Badr-Eldin, S. M., Ibrahim, T. S., Asfour, H. Z., Al-Rabia, M. W., Alfarsi, A., Alhakamy, N. A., Abdulaal, W. H., Al Sadoun, H., Helmi, N., Noor, A. O., Caraci, F., Almasri, D. M., & Caruso, G. (2020). The Enhanced Cytotoxic and Pro-Apoptotic Effects of Optimized Simvastatin-Loaded Emulsomes on MCF-7 Breast Cancer Cells. Pharmaceutics, 12(7), . https://doi.org/10.3390/pharmaceutics12070597
Awan, Zuhier A, et al. "The Enhanced Cytotoxic and Pro-Apoptotic Effects of Optimized Simvastatin-Loaded Emulsomes on MCF-7 Breast Cancer Cells." Pharmaceutics vol. 12,7 (2020). doi: https://doi.org/10.3390/pharmaceutics12070597
Awan ZA, Fahmy UA, Badr-Eldin SM, Ibrahim TS, Asfour HZ, Al-Rabia MW, Alfarsi A, Alhakamy NA, Abdulaal WH, Al Sadoun H, Helmi N, Noor AO, Caraci F, Almasri DM, Caruso G. The Enhanced Cytotoxic and Pro-Apoptotic Effects of Optimized Simvastatin-Loaded Emulsomes on MCF-7 Breast Cancer Cells. Pharmaceutics. 2020 Jun 27;12(7). doi: 10.3390/pharmaceutics12070597. PMID: 32604984; PMCID: PMC7407207.
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Pharmaceutics. 2020 Jun 27;12(7). doi: 10.3390/pharmaceutics12070597.

The Enhanced Cytotoxic and Pro-Apoptotic Effects of Optimized Simvastatin-Loaded Emulsomes on MCF-7 Breast Cancer Cells.

Pharmaceutics

Zuhier A Awan, Usama A Fahmy, Shaimaa M Badr-Eldin, Tarek S Ibrahim, Hani Z Asfour, Mohammed W Al-Rabia, Anas Alfarsi, Nabil A Alhakamy, Wesam H Abdulaal, Hadeel Al Sadoun, Nawal Helmi, Ahmad O Noor, Filippo Caraci, Diena M Almasri, Giuseppe Caruso

Affiliations

  1. Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  2. Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  3. Advanced Drug Delivery Research Group, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  4. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
  5. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  6. Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  7. Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  8. King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  9. Department of Biochemistry, Cancer Metabolism and Epigenetic Unit, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  10. Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589.
  11. Department of Medical Laboratory Technology, College of Applied Medical Sciences, University of Jeddah, Jeddah, Saudi Arabia.
  12. Department of Biochemistry, College of Sciences, University of Jeddah, Jeddah, Saudi Arabia.
  13. Pharmacy Practice Department, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  14. Oasi Research Institute-IRCCS, Via Conte Ruggero, 73, 94018 Troina (EN), Italy.
  15. Department of Drug Sciences, University of Catania, 95125 Catania, Italy.

PMID: 32604984 PMCID: PMC7407207 DOI: 10.3390/pharmaceutics12070597

Abstract

Statins, including simvastatin (SMV), are commonly used for the control of hyperlipidaemia and have also proven therapeutic and preventative effects in cardiovascular diseases. Besides that, there is an emerging interest in their use as antineoplastic drugs as demonstrated by different studies showing their cytotoxic activity against different cancer cells. In this study, SMV-loaded emulsomes (SMV-EMLs) were formulated and evaluated for their cytotoxic activity in MCF-7 breast cancer cells. The emulsomes were prepared using a modified thin-film hydration technique. A Box-Behnken model was used to investigate the impact of formulation conditions on vesicle size and drug entrapment. The optimized formulation showed a spherical shape with a vesicle size of 112.42 ± 2.1 nm and an entrapment efficiency of 94.34 ± 1.11%. Assessment of cytotoxic activities indicated that the optimized SMV-EMLs formula exhibited significantly lower half maximal inhibitory concentration (IC50) against MCF-7 cells. Cell cycle analysis indicated the accumulation of cells in the G2-M phase as well as increased cell fraction in the pre-G1 phase, suggesting an enhancement of anti-apoptotic activity of SMV. The staining of cells with Annex V revealed an increase in early and late apoptosis, in line with the increased cellular content of caspase-3 and Bax. In addition, the mitochondrial membrane potential (MMP) was significantly decreased. In conclusion, SMV-EMLs demonstrated superior cell death-inducing activity against MCF-7 cells compared to pure SMV. This is mediated, at least in part, by enhanced pro-apoptotic activity and MMP modulation of SMV.

Keywords: apoptosis; breast cancer; cell cycle; cytotoxicity; emulsomes; simvastatin

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