Daucosterol from Crateva adansoniiDC (Capparaceae) reduces 7,12‐dimethylbenz(a)anthracene‐induced mammary tumors in Wistar rats

Abstract

This study aimed to evaluate the in vivo anticancer effects of daucosterol which was earlier reported to possess in vitro anticancer effects. Breast tumor was induced in 30 rats using the environmental carcinogen 7,12‐dimethylbenz(a)anthracene (DMBA) while 6 control rats received olive oil (NOR). Animals with palpable tumors were randomized into five groups (n = 6) each as follows: negative control group treated with the vehicle (DMBA); positive control group treated with 5 mg/kg BW doxorubicin (DOXO + DMBA); three groups treated with daucosterol at doses of 2.5, 5, and 10 mg/kg BW (DAU + DMBA). Treatment lasted 28 days afterward, tumor (mass, volume, cancer antigen [CA] 15‐3 level and histoarchitecture), hematological and toxicological parameters were examined. The tumor volume gradually increased in the DMBA group during the 28 days, with a tumor volume gain of ∼390 cm3. Daucosterol at all doses reduced tumor volume (∼133.7 cm3 at 10 mg/kg) as well as protein, malondialdehyde (MDA), and CA 15‐3 levels compared to DMBA rats. Tumor sections in daucosterol‐treated rats showed a lower proliferation of mammary ducts with mild (5 and 10 mg/kg) to moderate (2.5 mg/kg) inflammatory responses. Moreover, it exhibited an antioxidant effect, evidenced by a significant and dose‐dependent decreased in MDA levels, as well as an increase in catalase activity compared to the DMBA group. Daucosterol showed for the first time in vivo antitumor effects that corroborate its previous in vitro effects.

Oral administration of tartrazine (E102) accelerates the incidence and the development of 7,12-dimethylbenz(a) anthracene (DMBA)-induced breast cancer in rats

“…These results are consistent with the higher tumor incidence, tumor weight and tumor volume observed in DMBA + TARZ group as compared to the DMBA group. These high levels of CA 15–3 and α-fetoprotein portray the establishment of cancer and are in agreement with the observations of Nguedia et al [ 31 ]. Several studies have demonstrated the undeniable role of oxidative stress in the carcinogenesis of the human breast; this generally results from an established imbalance between pro-oxidant and anti-oxidant [ 38 ].…”

“…Indeed this model is acclaimed for the histological and molecular similarities with human mammary cancer. DMBA is an environmental chemical carcinogen that induces genotoxicity via its hepatic 3,4-dihydrodiol-1,2-epoxide metabolites and the free radicals they generate [ 31 ]. The results obtained from this work showed that the incidence of mammary tumors was higher in animals exposed to DMBA and treated with tartrazine (100%) compared to animals exposed only to DMBA (80%), suggesting that tartrazine increases the incidence of mammary tumors in animals in which cancer has been initiated.…”

“…It is involved in the regulation of proliferation, differentiation and survival of different cell types, both embryonic and tumor [ 36 ]. As far as it is concerned, CA 15–3 is a biomarker of breast cancer overexpressed during cell proliferation [ 31 ]. Estradiol is the main female sex hormone of a steroid nature, involved in breast carcinogenesis as initiator and promoter [ 37 ].…”

Histopathological study of the protective effect of vitamin E against DMBA induced mammary cancer in rats

“…The first group administered corn oil (0.2 mL/rat) by gastric tube, fed on basal diet according to Kilany et al [12] and served as control. The second group administered Vit E (100mg/Kg B.W/d) by gastric tube dissolved in 4 mL corn oil as reported by Abdo et al [13].The third group administered corn oil (0.2 mL/rat) by gastric tube and subcutaneously injection with a single dose of 50 mg/kg BW of DMBA to induce mammary tumor in rats of ~55 days of age as reported by Nguedia et al [14]. The fourth group administered Vit E 21 days before DMBA injection & continued for 6 months.…”

Phytosterols and phytostanols and the hallmarks of cancer in model organisms: A systematic review and meta-analysis

“…Lipid peroxidation (LPO) is a mechanism that induces onset and progression of carcinogenesis through the production of reactive compounds like malondialdehyde (MDA). Ali et al (2015) and Nguedia et al (2020) showed that DMBA induced LPO, measured through MDA levels, is significantly reduced by STIG or DAUC relative to controls in mutagenic models of skin papilloma and breast cancer, respectively. However, while STIG increased the levels of superoxide dismutase (SOD), catalase (CAT) and the reduced form of glutathione (GSH), which are essential for reactive oxygen species (ROS) catalysis, DAUC increased only CAT activity (Nguedia et al 2020), suggesting a weaker ability to induce endogenous antioxidant mechanisms compared to STIG.…”