Abstract:
Breast cancer (BC) remains a disease with high morbidity and mortality. In Nigeria,
BC represents about 23% of all cancer cases. Currently available chemotherapeutic
interventions are associated with significant adverse effects, hence the need for safer
options. C. portoricensis (CP) has been applied to manage breast diseases in
ethnomedicine. However, there is paucity of scientific basis to justify this claim. In this
study, an investigation of the effects of CP on N-nitroso-N-methylurea (MNU) and
Benzo(a)pyrene (BP)-induced mammary and reproductive organ toxicity in Wistar rats
was conducted.
A root bark sample of CP was taken from Ikire, Osun State and authenticated at Forest
Hebarium Ibadan (FHI:111949). The methanol extract of CP (MCP) was obtained
from the powdered root. The MCP was partitioned to obtain n-hexane, chloroform,
ethylacetate and butanol fractions. The chloroform fraction of CP (CCP) was subjected
to biochemical assay using MCF-7 cells. Sixy-four female Wistar rats (30-40g) were
divided into eight groups (n=8): Vehincle, MNU, [MNU+MCP (100 mg/kg)],
[MNU+MCP (200 mg/kg)], [MNU+MCP (300 mg/kg)], MCP (300 mg/kg),
[MNU+Vincasar (0.5 mg/kg)] and Vincasar only. In another study, fifty-six female
rats were grouped into seven (n=8): Vehincle, [MNU+BP], [MNU+BP+CCP (50
mg/kg)], [MNU+BP+CCP (100 mg/kg)], CCP (100 mg/kg), [MNU+BP+ Vincasar]
and Vincasar only. The MNU (50 mg/kg) and BP (50 mg/kg) were administered
intraperitoneally at age 7, 10 and 13 weeks. The MCP and CCP were administered
orally thrice weekly. Rats were sacrificed; blood and tissues (mammary and uterine)
were obtained for analyses. Lactate dehydrogenase (LDH), Superoxide Dismutase
(SOD), Catalase, Glutathione-S-Transferase (GST), Glutathione Peroxidase (GPx),
malondialdehyde, Nitric Oxide (NO) and Myeloperoxidase were determined by visspectrophotometry. Cyclooxygenase-2, inducible Nitric Oxide Synthase (iNOS), B-cell
lymphoma-2 (Bcl-2), p53, Interleukins-1β and 6 (IL-1β, IL-6), Estrogen and
Progesterone receptors (ER+, PR+) and Epidermal Growth Factor Receptor-2 (EGFR-
2) were determined by immunohistochemistry. Micro-section of tissues were subjected
to Hematoxylin & Eosin and examined under the light microscope. Data were analysed
using ANOVA at α0.05.ix
The CCP decreased levels of IL-1β (34%), LDH (24%), MPO (74%), malondialdehyde
(55%) and increased the activities of SOD (48%) and catalase (49%) in MCF-7 cells.
The MNU decreased activities of mammary SOD (22%), uterine CAT (24%) and, GST
(25%) relative to Vehincle. The MCP (100 mg/kg) when compared with MNU
significantly elevated mammary SOD (18%) and uterine GST (20%). Treatment with
CCP (100 mg/kg) when compared with MNU+BP significantly increased the
mammary catalase (24.42±4.86 vs 16.1p6±2.90), GPx (171.48±13.97 vs 93.68±5.06),
SOD (25.16±4.34 vs 16.09±2.90) and uterine catalase (29.52±4.83 vs 15.04±2.41) and
SOD (48.56±4.70 vs 21.42±0.35), respectively. Additionally, CCP (100 mg/kg)
significantly decreased mammary and uterine MPO (73%, 57%), NO (21%, 26%) and
malondialdehyde (10%, 31%) when compared with [MNU+BP]-treated rats. The CCP
(100 mg/kg) decreased ER+, PR+, EGFR-2, cyclooxygenase-2, iNOS, IL-6, IL-1β, Bcl-
2 and increased p53 expression in the mammary tissues of [MNU+BP+CCP]-treated
rats. Histology of mammary tissues showed atypical epithelia, high nucleocytoplasm
and ductal carcinoma in MNU+BP rats, which were reversed in rats given CCP (100
mg/kg).
C. portoricensis demonstrated chemopreventive effects via induction of apoptosis and
reduction of inflammatory cytokines.
