ABSTRACT
Apoptosis signaling pathways, drug resistance, and metastasis are important targets to develop new cancer treatments. We developed cholesterol-coated Poly(d,l-Lactide-co-Glycolic Acid) (PLGA) nanoparticles for effective encapsulation and delivery of retinoic acid and oxaliplatin to analyze their antitumor activity in colorectal cancer. The cell viability and proliferation of tumoral cells lines (CT-26 and SW-480) decreased when compared to control in vitro after treatment with the nanoparticles. In addition, apoptosis of CT-26 cells increased. Importantly, cytoprotection of nontumor cells was detected. Expression of pro-apoptotic proteins was upregulated, while anti-apoptotic proteins were downregulated either in vitro or in vivo. In addition, drug resistance and metastasis factors were downregulated in vivo. Human colorectal tumors that highly expressed BCL-2 and Ki-67 had a greater tendency towards death within 60 months. Our results show that loading oxaliplatin combined with retinoic acid and cholesterol in a nanoparticle formulation enables determination of optimal antitumor activity and subsequent treatment efficacy.
ABSTRACT
BACKGROUND: Spondias mombin has been used in folk medicine to treat inflammation in the oral cavity. This study aimed to evaluate the antioxidant and anti-inflammatory activity of S. mombin extract in an oral mucositis experimental model. METHODS: Male hamsters were orally pre-treated with hydroethanolic extract of S. mombin leaves (HESM) (50, 100, or 200â¯mg/kg) for ten days. Cheek pouch samples were subjected to macroscopic, histopathological and immunohistochemical analysis (Cox-2, iNOS, NF-kB p50 NLS and MMP-2). IL-1ß and TNF-α levels were analyzed by ELISA immunoassay, and Superoxide dismutase estimative (SOD), glutathione (GSH) and malondialdehyde (MDA) levels were submitted to spectroscopy analysis. RESULTS: The group treated with HESM at a dose of 200â¯mg/kg showed the best healing effect, showing no evidence of ulceration in the macroscopic analysis (pâ¯<â¯0.05). Histopathological analysis showed re-epithelialization, discrete mononuclear inflammatory infiltrate and absence of hemorrhage and edema score of 1 (1-1) (pâ¯<â¯0.05), as well as a large amount of collagen fibers and a lower immunoexpression of Cox-2, iNOS, NF-kB p50 NLS and MMP-2. Decrease in SOD (pâ¯<â¯0.05), MDA (p<0.001), IL-1ß (pâ¯<â¯0.05), and TNF-α levels (pâ¯<â¯0.001), with an increase in GSH (pâ¯<â¯0.01) levels. CONCLUSION: HESM (200â¯mg/kg) reduced oxidative stress and inflammation in the 5-fluorouracil-induced oral mucositis in hamsters.
