Abstract:
Estrogen signaling is crucial for breast cancer initiation and progression. Endocrine-based therapies
comprising estrogen receptor (ER) modulators and aromatase inhibitors remain the mainstay of
treatment. This study aimed at investigating the antitumor potential of the most potent compounds
in citrus peels on breast cancer by exploring their anti-estrogenic and anti-aromatase activities.
The ethanolic extract of diferent varieties of citrus peels along with eight isolated favonoids were
screened against estrogen-dependent breast cancer cell lines besides normal cells for evaluating their
safety profle. Naringenin, naringin and quercetin demonstrated the lowest IC50s and were therefore
selected for further assays. In silico molecular modeling against ER and aromatase was performed
for the three compounds. In vivo estrogenic and anti-estrogenic assays confrmed an anti-estrogenic
activity for the isolates. Moreover, naringenin, naringin and quercetin demonstrated in vitro
inhibitory potential against aromatase enzyme along with anticancer potential in vivo, as evidenced
by decreased tumor volumes. Reduction in aromatase levels in solid tumors was also observed in
treated groups. Overall, this study suggests an antitumor potential for naringenin, naringin and
quercetin isolated from citrus peels in breast cancer via possible modulation of estrogen signaling
and aromatase inhibition suggesting their use in pre- and post-menopausal breast cancer patients,
respectively.
