Synergistic Anti-Breast-Cancer Effects of Combined Treatment With Oleuropein and Doxorubicin In Vivo

Thesis
نوع عمل المنشور: 
published
مستخلص المنشور: 

Context • 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
Objective • 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.
Design • The research team designed in vivo (animal) and
in vitro (cell culture) studies.
Setting: The study was performed in the College of
Science of King Saud University in the University Center
for Women Students (Riyadh, Saudi Arabia).
Animals • The study involved 40 female, nude mice
(BALB/c OlaHsd-foxn1).
Intervention • 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.
Outcome Measures • The measures included the isolation
and primary culture of the tumor xenografts, apoptosis
analysis by annexin V, cellular lysate preparation, and
immunoblotting.
Results: 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.
Conclusions • The key findings clearly indicate the
synergistic efficacy of DOX with natural and nontoxic OL
against breast tumor xenografts. (Altern Ther Health Med.
[E-pub ahead of print.])

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