Date Published: December 09, 2019
Publisher: Sociedade Brasileira para o Desenvolvimento da Pesquisa em
Author(s): Keyla Borges Ferreira Rocha, Cláudia Nunes Oliveira, Ítalo Medeiros Azevedo, Robson de Macedo, Aldo Cunha Medeiros.
To examine the effects of Arrabidaa chica
(Bignoniacea) extract, a native plant of the Amazon
known as crajiru, on a 7,12-dimethyl-1,2-benzanthracene (DMBA)-induced
breast cancer model in Wistar rats.
We compared the response of breast cancer to the oral administration of
A. chica extract (ACE) for 16 weeks, associated or not
with vincristine. Groups: normal control; DMBA (50mg/kg v.o,) without
treatment; DMBA+ACE (300 mg/kg); DMBA+vincristine. 500μg/kg injected i.p;
DMBA+ACE+Vincristine 250μg/kg i.p. Imaging by microPET and fluorescence,
biochemistry, oxidative stress, hematology and histopathology were used to
validate the treatments.
All animals survived. A gradual weight gain in all groups was observed, with
no significant difference (p>0.05). The oral administration of ACE and
ACE+vincristine 50% significantly reduced breast tumors incidence examined
with PET-18FDG and fluorescence (p<0.001). Significant reduction of serum transaminases, oxidative stress and hematological toxicity were observed in these groups. Antioxidant enzyme levels in breast tissue were significantly higher compared to the DMBA and DMBA+vincristine groups. These results demonstrate for the first time that ACE positively influences the treatment of DMBA-induced breast cancer in animal model, inducing a reduction in oxidative stress and chemotherapy toxicity, meaning that ACE may have clinical implication in further studies.
Breast cancer is a major cause of morbidity and mortality among women. Worldwide, it
is the second most common type of cancer. There is a tendency for increased
mortality from breast cancer in Brazilian women1. Breast cancer originates from breast tissue, most commonly from the inner
lining of milk ducts or lobes that supply the ducts, and the main metastasis pathway
is the lymphatic system or the bloodstream2. Breast cancer may be induced by 7,12-dimethyl-1,2-benzanthracene (DMBA), a
procarcinogen with selectivity for female breast cancer. It undergoes metabolic
activation to carcinogenic dihydrodiolepoxide. Dihydrodiolepoxide binds to adenine
residues of deoxyribonucleic acid, resulting in mutagenesis and carcinogenesis3.
The project was approved by the institutional Commission of Ethics in the Use of
Animals (protocol 04/2018). All experimental procedures were performed based on the
guidelines of the Brazilian College of Animal Experimentation, as well as the
Brazilian Law No. 11.794/08. Wistar female rats (Rattus norvegicus)
weighing 185±23g from the Animal Science Center, UFRN, were used. Young (six week)
rats, more sensitive to DMBA, were used for breast tumor induction14. The rats were acclimatized for 1 week prior to the start of the experiment
under standard housing conditions, including room temperature 22-24°C, relative
humidity 40% and 12-hour light-dark cycle in polypropylene cages (maximum 2
animals/cage). The animals had ad libitum access to the rodent diet
(Prevence®) and water.
All animals survived after the experimental model procedures. The evolution of body
weights of the five study groups is shown in Figure
1. There was a gradual weight gain in all groups over 16 weeks. The
higher weight gain was observed in the control group rats, with no significant
difference between groups (p>0.05).
Normal structure with well-defined architecture was observed in the mammary tissue of
rats of the normal control group. Rats from the DMBA-induced cancer group showed
edema, neutrophil inflammation, and epidermal ulceration. Ductal carcinoma with
irregular cytoplasm, glandular cell multiplication and focal proliferation were
found in all rats of this group. DMBA+ACE group rats showed improvement in the
histological characteristics of the breast tissue. Neutrophil inflammation was
observed in the vicinity of the tumor. Ductal and epidermoid carcinomas were found
in ducts. Extensive apoptotic figures have been identified in the tumors. In the
DMBA+full-dose vincristine group adiponecrosis was identified near the tumor areas.
Apoptotic figures were present in ductal and epidermoid carcinoma. When breast
tumors were treated with DMBA+ACE+VIN50%, chronic inflammation was present in the
vicinity of neoplastic lesions. Apoptotic figures were identified in all ductal
carcinomas (Fig. 7 A-J).
Breast cancer is the most common cancer among women and the second leading cause of
cancer-related deaths worldwide. In 2012, 522,000 women died of breast cancer in
developed and developing countries17.
ACE acted as a therapeutic agent in a rat breast cancer model. The combination of ACE
and chemotherapy positively influenced the treatment of breast tumors, reduced the
effective dose of chemotherapy and attenuated some of its adverse effects.