Chemopreventive Potential of Santolina chamaecyparissus against MNU-Induced Mammary Cancer in Female Wistar Rats ^†

Abstract

Breast cancer is the most often diagnosed cancer worldwide, with the greatest fatality rate among women in 2021. Santolina chamaecyparissus L. has been shown to successfully inhibit cancer cells’ proliferation, especially in the human breast adenocarcinoma (MCF-7) cell line. This study’s goal was to evaluate the chemopreventive potential of a S. chamaecyparissus aqueous extract (SCE) on N-methyl-N-nitrosourea (MNU)-induced mammary cancer in female rats. This study was approved by the ORBEA under reference 834-e-CITAB-2020. Twenty-eight four-week-old female Wistar rats were divided into four groups: Control, MNU, SCE and SCE+MNU. SCE was supplemented in drinking water (120 µg/mL) ad libitum and replaced every 3 days due to the compounds’ stability. A total of nineteen compounds were identified in the extract, with myricetin-O-glucuronide and 1,3-O-dicaffeoylquinic acid being the main compounds found. At 50 days of age, the MNU was administered by intraperitoneal route. Humane Endpoint analysis was performed weekly. Induced animals were palpated twice a week. Tumour width (W) and length (L) were weekly measured with a calliper. Tumour volume was also determined [V = (W² × L)/2]. After twenty-one weeks, animals were sacrificed by a ketamine/xylazine overdose. Control and SCE animals did not develop any tumours. In the MNU group, the first tumour appeared during the ninth week; in SCE+MNU, it only appeared in the sixteenth week. No significant differences were found. However, the tumour incidence in SCE+MNU (28.57%) was lower than in MNU (57.14%). The MNU group had a higher mean tumour weight (2.31 ± 1.13 g) than the SCE+MNU group (0.39 ± 0.02 g) and a larger mean tumour volume (2.02 ± 1.23 cm³) than SCE+MNU (0.57 ± 0.15 cm³) (p > 0.05). Despite the lack of statistically significant differences between groups, the absence of mortality in SCE+MNU, as well as the lower values in each parameter, suggest that Santolina chamaecyparissus has interesting potential as a chemoprotective agent. Histopathological analysis will help understand this extract’s impact on oncogenesis.