ABSTRACT
OBJECTIVES: Combining tamoxifen, the most common breast cancer hormonal therapy, with natural antitumor substances may prevent its hyperplastic effects on the uterine endometrium. Dacryodes edulis (DE) is traditionally recommended for the treatment of cancerous diseases. To investigate its antiproliferative properties, the present study was designed to assess the ability of the combined administration of tamoxifen with the aqueous extract of DE leaves to inhibit the trophic effect of this hormone therapy on rat uterine endometrium without compromising its non-proliferative effect on breast tissue. METHODS: Ovariectomized (OVX) female Wistar rats were simultaneously treated with tamoxifen (10 mg/kg) intraperitoneally and DE leaves (at doses of 25, 50 and 100 mg/kgBW) by gavage. Control groups received either distilled water or tamoxifen alone. Treatments lasted 37 days. The 38th day, animals were sacrificed under anesthesia (diazepam: 10 mg/kgBW and ketamine: 50 mg/kgBW). The relative uterine weight was determined and the histological analysis of the uterus and mammary gland was performed. The oxidative status of the uterus was assessed and the levels of cholesterol and estradiol were evaluated in serum and uterus. RESULTS: Tamoxifen increased uterine weight and induced endometrial hyperplasia. This effect was associated with increased uterine levels of cholesterol (164.22%; p < 0.001), estradiol (927.5%; p < 0.001) and malondiadehyde (86%; p < 0.05), but unchanged antioxidant enzymes activities. The administration of DE leaves unchanged tamoxifen-increased uterine weight but reduced uterine epithelium hypertrophy (56.4%; p < 0.01). DE also increased uterine levels of malondiadehyde and antioxidant enzymes. The levels of estradiol and cholesterol in the uterus decreased while no changes were observed in the mammary gland of animals treated with tamoxifen alone or in co-administration with DE. CONCLUSIONS: D. edulis has antiproliferative properties and could complement endocrine therapy of estrogen-dependent breast cancer.
ABSTRACT
Breast cancer is the most common estrogen-dependent cancer in the world. Hormone therapy for this cancer can be neoadjuvant and/or adjuvant. Herbal remedies with antiproliferative properties are believed to be potential anticancer agents. The aqueous extract of Dacryodes edulis (Burseraceae) leaves (AE), a medicinal plant used against cancer in Cameroon, was found to display antiproliferative effects in ovariectomized rats. Compounds isolated from this plant exhibited anticancer activity in vitro. To determine whether AE has an anticancer potential, its effects were investigated in rats with already developed breast cancer. Mammary tumors were induced by a single subcutaneous administration (under the mammary gland) of 7,12-dimethylbenz[a]anthracene (DMBA; 50 mg/kgBW) to immature female rats. After 22-26 weeks of observation, animals with palpable tumors were treated with tamoxifen (3.3 mg/kgBW) and AE at doses of 25 and 100 mg/kgBW. The negative control received distilled water. Treatments were given orally for 21 consecutive days. The volume of mammary tumors was evaluated weekly using a caliper. On day 22, animals were sacrificed. Cholesterol and estradiol levels were assessed in serum, breast tumors, mammary glands, and ovaries. Oxidative status of tumors was evaluated. The histological analysis of mammary glands and breast tumors was performed. Results showed that AE reduced tumor volume and weight (p < 0.05). This effect was associated with reduced cholesterol (p < 0.001) and estradiol (p < 0.01) levels in breast tumors, serum, ovaries, and mammary glands. AE also increased tumors levels of malondialdehyde (p < 0.05) and antioxidant enzymes (p < 0.01). These effects contributed to the decrease in the size of breast alveoli (p < 0.01), the density of cancer cells in breast tumors, and the invasion of these cells into the tumor connective tissue. In conclusion, the aqueous extract of D. edulis leaves, thanks to its ability to inhibit tumor growth, could be considered as a potential alternative for the neoadjuvant treatment of estrogen-dependent breast cancer.
ABSTRACT
Proliferation is a cellular process strongly linked to the genesis of cancer. Natural substances with antiproliferative activities are currently potential alternatives in the treatment of cancers. Dacryodes edulis, for instance, is a medicinal plant traditionally used in the treatment of cancer. Scientific studies have reported the antioxidant activity of this plant. In addition, the presence of prostate cancer chemopreventive polyphenols was reported in D. edulis extracts. Therefore, this study was aimed to evaluate the effects of the aqueous extract of D. edulis leaves on cell proliferation induced by estradiol in ovariectomized female Wistar rats. In this regard, ovariectomized (OVX) rats were cotreated with estradiol valerate (E2V) (0.75 mg/kg) and the aqueous extract of D. edulis leaves. Control groups received either the vehicle (sham-operated animals and the OVX control), E2V (0.75 mg/kg) only, or E2V (0.75 mg/kg) and tamoxifen (10 mg/kg). Treatments were administered orally for 3 consecutive days, and animals were sacrificed thereafter. Epithelial heights of the uterus and vagina were assessed. Uterine levels of total cholesterol and estradiol were determined as well. Results showed that the aqueous extract of D. edulis leaves reversed the effects of estradiol as it reduced uterine weight (p < 0.05), uterine (p < 0.05), and vaginal (p < 0.001) epithelium heights. This antiproliferative effect of D. edulis was associated with reduced tissue (uterine) levels of estradiol (p < 0.001). These results suggest that the aqueous extract of D. edulis leaves could be a potential alternative treatment for proliferation-related diseases.