Preclinical activity of fluvastatin-loaded self-nanoemulsifying delivery system against breast cancer models: Emphasis on apoptosis
Elimam, Hanan; Hussein, Jihan; Abdel-Latif, Yasmin; Abdel-Aziz, Amal Kamal; El-Say, Khalid M;
Abstract
Statins trigger apoptotic cell death in some types of growing tumor cells in a cholesterol-lowering-independent manner. Self-nanoemulsifying delivery systems (SNEDs) are potentially effective for the suppression of breast cancer development. This study aims to investigate the potential anticancer activity of fluvastatin (FLV)-SNEDs in breast cancer while comparing it with FLV in vitro as well as in vivo exploiting/using MDA-MB-231 and Erhlich ascites carcinoma (EAC)-bearing mice, respectively. Biochemical analysis of liver and kidney functions, oxidative stress markers, and histopathological examinations of such tumor tissues were performed showing the potentiality of SNEDs as a nanocarrier for antitumor agents. FLV-SNEDs demonstrated more potent anticancer activity compared to FLV on MDA-MB-231 and hepatocellular carcinoma (HepG2) cells. In vivo experiments on the EAC-bearing mice model indicated that FLV and-to a greater extent-FLV-SNEDs ameliorated EAC-induced hepatotoxicity and nephrotoxicity. FLV or FLV-SNEDs evidently reduced the percent of Ki-67 +ve EAC cells by 57.5% and 86.5% in comparison to the vehicle-treated EAC group. In addition, FLV or FLV-SNEDs decreased Bcl-2 levels in serum and liver specimens. In contrast, FLV or FLV-SNEDs significantly activated the executioner caspase-3. Simultaneously, both FLV and FLV-SNEDs stimulated p53 signaling and modulated Bcl-2 protein levels in treated cells. Collectively, these results support the contribution of apoptotic cell death in mediating the anticancer activities of FLV and FLV-SNEDs against murine EAC model in vivo. This study provides new understandings of how FLV and FLV-SNEDs regulate EAC cell viability via upregulation of p53 signaling, and through modulation of cleaved caspase-3 as well as antiapoptotic Bcl-2 marker.
Other data
Title | Preclinical activity of fluvastatin-loaded self-nanoemulsifying delivery system against breast cancer models: Emphasis on apoptosis | Authors | Elimam, Hanan; Hussein, Jihan; Abdel-Latif, Yasmin; Abdel-Aziz, Amal Kamal ; El-Say, Khalid M | Keywords | apoptosis; fluvastatin; p53; self-nanoemulsifying delivery system; triple-negative breast cancer | Issue Date | 2022 | Publisher | WILEY | Journal | Journal of cellular biochemistry | Volume | 123 | Issue | 5 | Start page | 947 | End page | 963 | ISSN | 0730-2312 1097-4644 |
DOI | 10.1002/jcb.30238 | PubMed ID | 35342983 | Scopus ID | 2-s2.0-85127293043 | Web of science ID | WOS:000773411900001 |
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