Liposomal curcumin inhibits Lewis lung cancer growth primarily through inhibition of angiogenesis

Abstract

Abstract. Curcumin has been proven to effectively inhibit tumor growth by both targeting tumor cells and angiogenesis; however, poor water solubility limits further clinical application. In the present study, we prepared water-soluble liposomal curcumin to investigate its anti-tumor effects and the underlying mechanism. The MTT assay was used to test the anti-proliferative activities for the MS1 murine endothelial and LL/2 Lewis lung cancer cell lines. Apoptosis and cell cycle arrest induced by liposomal curcumin were analysed by flow cytometry. Anti-angiogenic agents and the resulting anti-tumor effects were investigated in a murine lung cancer model. Zebrafish were used to investigate the anti-angiogenic effect of liposomal curcumin in the development of embryos. In vitro, liposomal curcumin inhibited the proliferation of MS1 cells and induced cell cycle arrest and apoptosis. Notably, LL/2 cells showed less sensitivity to the liposomal curcumin in vitro. In vivo, the systemic administration of liposomal curcumin resulted in significant inhibition of tumor growth. CD31 immunohistochemical analysis and alginate encapsulation assay revealed that angiogenesis was decreased by liposomal curcumin treatment. Angiogenesis was also suppressed in the development of zebrafish. Liposomal curcumin showed potent inhibitory activity against murine endothelial cells but not lung cancer cells. Liposomal curcumin treatment is capable of significantly inhibiting tumor growth in vivo, a process that may depend primarily on its anti-angiogenic effects. Our study also indicates that liposomal curcumin may be developed not only for cancer therapy, but also for the treatment of other angiogenesis-related diseases. IntroductionCurcumin has been proven to be a promising anti-cancer drug by induction of apoptosis and apoptosis-independent death, and inhibition of proliferation and angiogenesis (1-4). Phase I and II studies of this compound have shown that curcumin is well tolerated and is effective for cancer patients; however, its benefits may be attenuated due to its low bioavailability through oral administration for non-gastrointestinal cancers (5,6). Therefore, novel strategies are required to overcome these limitations, which are mostly due to the low water solubility and low stability of curcumin against gastrointestinal fluids (7). Investigators have recognized that liposomes have the advantage of improving water insolubility and enhancing delivery efficacy of drugs (8). At present, various methods have been reported for the preparation of liposomes (9). Curcumin acts as an anticancer drug through multiple mechanisms; however, the activity of curcumin may be changed in a liposomal form. Furthermore, the water solubility of liposomal curcumin provides a new strategy for intravenous administration. It is speculated that, systemically, intravenous administration may exhibit marked inhibitory effects due to circumvention of the first-pass effect. Angiogenesis, the process by which capillaries sprout from pre-existing vasculature, is...

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Liposome-Encapsulated Curcumin-Loaded 3D Printed Scaffold for Bone Tissue Engineering

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“…However, the results of phase I and II clinical studies of curcumin in other types of malignancies such as the skin, the liver and pancreatic cancer have not supported the preclinical observations due to the low stability and limited absorption of EGCG [143,144]. An interesting study was conducted by Wang L et al in which they demonstrated the potential anti-cancer effect of using water-soluble liposomal curcumin on Lewis lung cancer in vitro and in vivo by suppressing angiogenesis [145]. This liposomal form of curcumin could overcome problems associated with previous clinical trials and may show a better improvement in the overall survival of cancer patients.…”