Liposomal β-Sitosterol Suppresses Metastasis of CT26/luc Colon Carcinoma via Inhibition of MMP-9 and Evoke of Immune System

Abstract

β-sitosterol (SITO) has been reported with anticancer effects; however, with poor bioavailability. The current study aimed to investigate whether liposomal encapsulated β-sitosterol (LS) has a better inhibition effect on tumor metastasis than β-sitosterol in a CT26/luc lung metastasis mouse model and the possible underlying mechanism. LS was liposomal-encapsulated SITO and was delivered to mice by oral gavage. The cell viability was determined by the MTT assay, and invasiveness of the tumor cells and related protein expression were evaluated with the invasion assay and Western blotting. For therapeutic efficacy evaluation, male BALB/c mice were treated with PBS, SITO, and LS once a day for 7 days prior to intravenous injections of CT26/luc cells; treatments were continued twice a week post-cell inoculation throughout the entire experiment. Tumor growth inhibition was monitored by bioluminescent imaging (BLI). IL-12, IL-18, and IFN-γ in the intestinal epithelium were determined by ELISA. The results show that LS treatment had a better invasion inhibition with lower cytotoxicity than SITO when the same dose was utilized. Notably, mice treated with LS significantly exhibited fewer metastases to the lungs and other tissues/organs compared with the Control and SITO groups. Additionally, the IL-12, IL-18, and IFN-γ levels were significantly increased in the LS-treated mice compared with the Control and SITO groups. The underlying mechanism may be through the inhibition of MMP-9 and elicitation of the antitumoral Th1 immune response, such as increasing CD4+ and CD8+ T cells, IL-12, IL-18, and IFN-γ.

Ligusticum chuanxiong Hort. Ameliorates Neuropathic Pain by Regulating Microglial M1 Polarization: A Study Based on Network Pharmacology

“…Previous studies have shown that β-sitosterol exerts anti-inflammatory and cholesterol-lowering effects. 30 It can also reduce the severity of NP in diabetic mice. 31 For these reasons, in the present work β-sitosterol was selected to explore the potential analgesic mechanism of LCH.…”

Phytochemical Study of Euphorbia turcomanica Boiss.

“…Compound 5 is a commonly occurring phytosterol called β-sitosterol, which is a key component present in plants. Out of the many pharmacological and biological effects that have been reported for this compound over the past decades, anti-inflammatory, angiogenic, antiadipogenic, anti-diabetic, anti-oxidant, anti-cancer, immunomodulatory activities and a role in cardiovascular diseases prevention can be mentioned, reported from recent findings that can be beneficial in drug developments and other therapeutic applications [45][46][47][48][49][50][51]. The hypocholesterolemic effects of E. hirta and its role in curing obesity have been linked to this natural compound [22], as well as the larvicidal activity of E. thymifolia [21].…”

The Role of MMP-9 and MMP-9 Inhibition in Different Types of Thyroid Carcinoma

“…Liposomal encapsulated β-SITO (LS), synthesized by the thin-film hydration method using egg phosphatidylcholine (EPC), shows better invasion inhibition, lower cytotoxicity, and fewer metastases to other tissues compared with SITO when treating colon carcinoma. The inhibition of MMP-9 and the elicitation of anti-tumor immune response generated by LS further prove it to be a more promising anti-tumor drug [31].…”