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- Title
Synergistic Anti-Breast-Cancer Effects of Combined Treatment With Oleuropein and Doxorubicin In Vivo.
- Authors
Elamin, Maha H.; Elmahi, Abdelsalam B.; Daghestani, Maha H.; Al-Olayan, Ebtesam M.; Al-Ajmi, Reem A.; Alkhuriji, Afrah F.; Hamed, Sherifa S.; Elkhadragy, Manal F.
- Abstract
<bold>Context: </bold>Breast cancer is a leading cause of cancer fatalities among women worldwide. Of the more than 80% of patients who receive adjuvant chemotherapy, approximately 40% relapse. The majority of these patients die of disseminated metastatic disease, which emphasizes the need for new therapeutic strategies.<bold>Objective: </bold>The study intended to investigate the anticancer effects of oleuropein (OL) and doxorubicin (DOX) individually and in combination on breast tumor xenografts and also to evaluate the molecular pathways involved.<bold>Design: </bold>The research team designed in vivo (animal) and in vitro (cell culture) studies.<bold>Setting: </bold>The study was performed in the College of Science of King Saud University in the University Center for Women Students (Riyadh, Saudi Arabia).<bold>Animals: </bold>The study involved 40 female, nude mice (BALB/c OlaHsd-foxn1).<bold>Intervention: </bold>The mice were injected subcutaneously with MDA-MB-231 human breast cancer cells. After the growth of tumors, the animals were randomly divided into 4 groups to receive intraperitoneal injections: (1) group 1 (control group)-dimethyl sulfoxide, (2) group 2 (intervention group)-50 mg/kg of OL, (3) group 3 (intervention group)-2.5 mg/kg of DOX, and (4) group 4 (intervention group)-1.5 mg/kg of DOX, immediately followed by 50 mg/kg of OL. The OL was extracted from Manzanillo olive trees (Olea europaea) grown in Tabouk, Saudi Arabia.<bold>Outcome Measures: </bold>The measures included the isolation and primary culture of the tumor xenografts, apoptosis analysis by annexin V, cellular lysate preparation, and immunoblotting.<bold>Results: </bold>The volume of the tumor increased aggressively, reaching 173 mm3 in the control animals in a time-dependent manner. On the other hand, a sharp drop, to 48.7 mm3, in the volume of the tumor was observed with the 2 drugs combined, a more than 3-fold decrease. The effect was mediated through the induction of apoptosis via the mitochondrial pathway. The combined treatment downregulated the antiapoptosis and proproliferation protein, nuclear factor-kappa Β, and its main oncogenic target cyclin D1. Furthermore, it inhibited the expression of BCL-2 and survivin. This inhibition could explain the cooperative suppression of the proliferation of breast tumor xenografts and the induction of apoptosis by the combined effect of the compounds used.<bold>Conclusions: </bold>The key findings clearly indicate the synergistic efficacy of DOX with natural and nontoxic OL against breast tumor xenografts.
- Subjects
DOXORUBICIN; HETEROCYCLIC compounds; ANTINEOPLASTIC antibiotics; ANIMAL experimentation; APOPTOSIS; BREAST tumors; CANCER relapse; CELL lines; CELL physiology; MICE; THERAPEUTICS
- Publication
Alternative Therapies in Health & Medicine, 2019, Vol 25, Issue 3, p17
- ISSN
1078-6791
- Publication type
journal article