TY - JOUR
T1 - The antimammary tumor effects of ethanolic extract of propolis from Adamawa region (Cameroon) are by apoptosis via reactive oxygen species-mediated mitochondrial pathway
AU - Zingue, Stéphane
AU - Cisilotto, Julia
AU - Fogang, Robinson Charly Mbe
AU - Tchoupang, Edwige Nana
AU - Ndinteh, Derek Tantoh
AU - Tchuenguem Fohouo, Nestor Fernand
AU - Njamen, Dieudonné
AU - Creczynski-Pasa, Tânia Beatriz
N1 - Publisher Copyright:
© 2021 Wiley Periodicals LLC.
PY - 2021/5
Y1 - 2021/5
N2 - Identification of novel natural treatment to combat cancer is a current need. This study was aimed at assessing the anticancer effects of ethanol-extracted Cameroonian propolis (EEP). The antitumor effect of EPP was evaluated in vitro by measuring; cell viability, cell cycle, cell death mechanism, cell migration/invasion, reactive oxygen species (ROS), mitochondrial potential (ΔΨm), caspase activity, and apoptosis-regulating proteins (Bcl-2 and Bcl-XL) in cell lines. In vivo, the effect of EEP against 7,12 dimethylbenz(a)anthracene (DMBA)-induced breast tumorigenesis in rats was assessed. EEP was found to induce cytotoxicity against ER negative MDA-MB-231 breast cancer cells by activating apoptosis through ROS-mediated mitochondrial pathway. The extract equally triggered caspase-3 and caspase-9, increment of ROS level, disruption of ΔΨm and down-regulation of Bcl-XL and Bcl-2 proteins. Besides, EPP prevented migration and invasion activities by inhibiting MMP-2 activity. At all doses it prevented breast tumor incidence (20% in EEP 150 mg/kg vs 70% in DMBA) as well as tumor burden. Tumor sections from EEP-treated rats showed middle proliferation of mammary ducts with weak inflammatory responses. In summary, Cameroonian propolis exhibited antimammary tumor effects via the intrinsic pathway of apoptosis.
AB - Identification of novel natural treatment to combat cancer is a current need. This study was aimed at assessing the anticancer effects of ethanol-extracted Cameroonian propolis (EEP). The antitumor effect of EPP was evaluated in vitro by measuring; cell viability, cell cycle, cell death mechanism, cell migration/invasion, reactive oxygen species (ROS), mitochondrial potential (ΔΨm), caspase activity, and apoptosis-regulating proteins (Bcl-2 and Bcl-XL) in cell lines. In vivo, the effect of EEP against 7,12 dimethylbenz(a)anthracene (DMBA)-induced breast tumorigenesis in rats was assessed. EEP was found to induce cytotoxicity against ER negative MDA-MB-231 breast cancer cells by activating apoptosis through ROS-mediated mitochondrial pathway. The extract equally triggered caspase-3 and caspase-9, increment of ROS level, disruption of ΔΨm and down-regulation of Bcl-XL and Bcl-2 proteins. Besides, EPP prevented migration and invasion activities by inhibiting MMP-2 activity. At all doses it prevented breast tumor incidence (20% in EEP 150 mg/kg vs 70% in DMBA) as well as tumor burden. Tumor sections from EEP-treated rats showed middle proliferation of mammary ducts with weak inflammatory responses. In summary, Cameroonian propolis exhibited antimammary tumor effects via the intrinsic pathway of apoptosis.
KW - apoptosis
KW - breast cancer
KW - Cameroonian propolis
KW - chemoprevention
KW - DMBA
UR - http://www.scopus.com/inward/record.url?scp=85099113024&partnerID=8YFLogxK
U2 - 10.1002/tox.23089
DO - 10.1002/tox.23089
M3 - Article
C2 - 33393727
AN - SCOPUS:85099113024
SN - 1520-4081
VL - 36
SP - 861
EP - 873
JO - Environmental Toxicology
JF - Environmental Toxicology
IS - 5
ER -