RESUMEN
Colorectal cancer (CRC) poses a significant global health burden, being the third most prevalent cancer and the second most significant contributor to cancer-related deaths worldwide. Preventive strategies are crucial to combat this rising incidence. 6-shogaol, derived from ginger, has shown promise in preventing and treating various cancers. This study investigated the preventive effects of 6-shogaol on azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced CRC in mice. Forty male BALB/c mice were randomly divided into control, 6-shogaol, AOM + DSS, and 6-shogaol + AOM + DSS. Mice in the control group received corn oil for 16 weeks, while those in the 6-Shogaol group were administered 20 mg/kg of 6-shogaol for 16 weeks. The AOM + DSS group received a single intraperitoneal dose (ip) of 10 mg/kg of AOM, followed by three cycles of 2.5% DSS in drinking water. The 6-shogaol + AOM + DSS group received both 6-shogaol for 16 weeks and a single ip of 10 mg/kg of AOM, followed by three cycles of 2.5% DSS in drinking water. The AOM + DSS-treated mice exhibited reduced food consumption, colon weight, and colon length, along with increased tumor formation. Co-administration of 6-shogaol effectively reversed these changes, inhibiting CRC development. Histopathological analysis revealed protective effects of 6-shogaol against colonic insults and modulation of inflammatory responses. 6-shogaol significantly reduced Carcinoembryonic antigen and Kiel 67 levels, indicating inhibition of tumor cell proliferation. Mechanistically, 6-shogaol promoted apoptosis by upregulating protein 53 and caspase-3 expression, and it effectively restored the balance of the Wingless-related integration site signaling pathway by regulating ß-catenin and adenomatous polyposis coli levels. Moreover, 6-shogaol demonstrated anti-inflammatory effects, reducing myeloperoxidase, Tumor necrosis factor alpha, and cyclooxygenase-2 levels in AOM/DSS-treated mice. Additionally, 6-shogaol restored redox homeostasis by reducing lipid peroxidation and nitrosative stress and enhancing antioxidant enzyme activities. The findings suggest that 6-shogaol inhibits cell proliferation, induces apoptosis, regulates Wnt signaling, suppresses inflammation, and restores redox homeostasis, providing comprehensive insights into its potential therapeutic benefits for CRC.
RESUMEN
Colorectal adenoma appears as benign lesions and is a precursor of colorectal adenocarcinoma. The effect of 6-Shogaol (6-[S]), a bioactive agent from ginger, in early colonic adenoma growth is unknown. As a result, this study examines the effect of 6-[S] in a mouse colorectal adenoma model induced by Azoxymethane (AOM) and dextran sulfate sodium (DSS). Adult male mice served as control in Group 1. Group 2 was treated orally with 6-[S] extract (20 mg/kg BW). Group 3 was exposed to AOM (25 mg/kg BW, ip) and one cycle of DSS (2.5%) in drinking water alone while Group 4 was co-treated with 6-[S] for twenty-one (21) days. The body weight gain, organ weight and length, oxidative stress indices, inflammatory markers and histological examination were estimated. Our findings show that 6-[S] co-treatment reversed AOM/DSS-induced elevation in colon weight, colon length, nitric oxide (NO), myeloperoxidase (MPO), hydrogen peroxidase (H2 O2 ), and tumor necrosis factor-alpha (TNF-α). However, the antioxidant enzyme activities measured namely catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), and glutathione-S-transferase were significantly increased in 6-[S] treated mice. Taken together, the protective effect of 6-[S] on oxidative burden, inflammation, and histological aberration observed in the colon of the AOM/DSS model of adenoma growth in mice is mediated primarily owing to its anti-inflammatory and anti-oxidative properties. Thus, this study reveals 6-[S] as a useful agent in the possible clinical intervention of colorectal adenoma. PRACTICAL APPLICATIONS: Certain spices have been reported to have numerous phytochemicals with numerous medicinal purposes. However, no studies have been conducted to investigate the role of 6-[S], a phytochemical found in ginger, in the treatment of colorectal adenoma. The study's findings show that 6-[S] is protective in early colonic cancer development, as it manages colorectal adenoma cancer models of AOM/DSS. As a result, 6-[S]'s ability to reduce oxidative stress and inflammation in the colon may be a potential nutritional therapeutic adjuvant for colorectal adenoma.