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.

Highlights

  • Cell proliferation is the process strongly involved in cancer genesis [1]. is latter represents the main cause of death all over the world, with 19.3 million cases and 10 million deaths in 2020 [2]

  • In order to provide more scientific evidence to the probable anticancer potential of D. edulis, we propose to evaluate the effects of the aqueous extract of D. edulis leaves in animals with an already developed breast cancer. e effects of the aforementioned extract were investigated on tumor growth, the oxidative status of breast tumors, and the histomorphology of breast tumors and mammary glands. e determination of serum and tissue levels of total cholesterol and estradiol allowed elucidating the probable mechanism of action of this plant

  • A similar decrease was observed with the aqueous extract of D. edulis leaves at tested doses [tumor weight: 2.44 ± 0.49 g (36.95% decrease; p < 0.05) at 25 mg/kgBW and 1.95 ± 0.39 g (49.61% decrease; p < 0.001) at 100 mg/kgBW], as compared to the dimethylbenz[a] anthracene (DMBA) + DW control group

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Summary

Introduction

Cell proliferation is the process strongly involved in cancer genesis [1]. is latter represents the main cause of death all over the world, with 19.3 million cases and 10 million deaths in 2020 [2]. A phytochemical assay we recently performed [4] with the aqueous extract of D. edulis leaves indicated the presence of a wide range of bioactive compounds (flavonoids, phenols, alkaloids, and flavonols) endowed with antiproliferative and anticancer activities [29] This plant extract was reported to inhibit cell growth and proliferation induced by estradiol on the uterus and vagina of female Wistar rats [4], supporting in part the hypothesis according to which this plant may help against cancer diseases [28]. In order to provide more scientific evidence to the probable anticancer potential of D. edulis, we propose to evaluate the effects of the aqueous extract of D. edulis leaves in animals with an already developed breast cancer. e effects of the aforementioned extract were investigated on tumor growth, the oxidative status of breast tumors, and the histomorphology of breast tumors and mammary glands. e determination of serum and tissue (breast tumors, mammary glands, and ovaries) levels of total cholesterol and estradiol allowed elucidating the probable mechanism of action of this plant

Materials and Methods
Biochemical Analysis
Results
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