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Repurposing of fluvastatin as an anticancer agent against breast cancer stem cells via encapsulation in a hyaluronan-conjugated liposome

Authors
Yu, Ji SuKim, Jin SeokShin, Dae Hwan
Issue Date
Dec-2020
Publisher
MDPI AG
Keywords
Breast cancer stem cells; Drug delivery system; Fluvastatin; Hyaluronan; Liposome
Citation
Pharmaceutics, v.12, no.12, pp 1 - 13
Pages
13
Journal Title
Pharmaceutics
Volume
12
Number
12
Start Page
1
End Page
13
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/998
DOI
10.3390/pharmaceutics12121133
ISSN
1999-4923
Abstract
Fluvastatin (FLUVA), which is a common anti-hypercholesterolemia drug, exhibits potential anticancer activity as it suppresses the proliferation, angiogenesis, and metastasis of breast cancer cells via inhibiting 3-hydroxy-methyl glutaryl-coenzyme A (HMG-CoA) reductase. In this study, hyaluronan-conjugated FLUVA-encapsulating liposomes (HA-L-FLUVA) were evaluated for their anticancer efficacy in vitro and in vivo. The particle size, zeta potential, and encapsulation efficiency of HA-L-FLUVA were 158.36 ± 1.78 nm, −24.85 ± 6.26 mV, and 35%, respectively. Growth inhibition of breast cancer stem cells (BCSCs) by HA-L-FLUVA was more effective than that by free FLUVA. The half maximal inhibitory concentration (IC50 ) values of FLUVA, L-FLVUA, and HA-L-FLUVA were 0.16, 0.17, and 0.09 µM, respectively. The in vivo anticancer effect of HA-L-FLUVA in combination with doxorubicin (DOX) was more effective than that of free FLUVA, free DOX, and HA-L-FLUVA. The longest survival of mice was achieved by treatment with FLUVA (15 mg/kg) and HA-L-FLUVA (15 mg/kg) + DOX (3 mg/kg), followed by HA-L-FLUVA (15 mg/kg), Dulbecco’s phosphate buffered saline, and DOX (3 mg/kg). No more than 10% body weight loss was observed in the mice injected with FLUVA, indicating that the drug was not toxic. Taken together, these results indicate that HA-L-FLUVA could serve as an effective anticancer drug by inhibiting the growth of both breast cancer cells and cancer stem cells. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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