Title:In Vivo Inhibition of Proteasome Activity and Tumour Growth by Murraya koenigii Leaf Extract in Breast Cancer Xenografts and by Its Active Flavonoids in Breast Cancer Cells
VOLUME: 16 ISSUE: 12
Author(s):Bindu Noolu, Ramesh Gogulothu, Mehrajuddin Bhat, Syed S.Y.H. Qadri, V. Sudhakar Reddy, G. Bhanuprakash Reddy and Ayesha Ismail
Affiliation:Department of Endocrinology & Metabolism, National Institute of Nutrition, Jamai Osmania, PO, Tarnaka, Hyderabad, India- 500007.
Keywords:Apoptosis, breast cancer, flavonoid, Murraya koenigii, proteasome, xenografts.
Abstract:Inhibition of the 26S proteasome is an attractive approach for anticancer therapy.
Proteasome inhibitors are known to selectively target cancer cells and make them more sensitive
to chemotherapeutic agents. Murraya koenigii is a medicinally important herb of Asian origin
and a rich source of bioactive compounds such as flavonoids and alkaloids. In the present study,
we investigated the proteasome inhibitory and apoptotic effect of M. koenigii leaf extract in vivo
in a xenograft tumor mouse model, and also assessed the toxicity if any in normal mice. M.
koenigii extract did not lead to any toxicity in mice. Analysis of extract revealed the presence of
flavonoid compounds which act as proteasome inhibitors. Quercetin treatment led to the
decrease in the cell viability and arrest of cells in G2/M phase. Quercetin, Apigenin, Kaempferol
and Rutin; flavonoids present in the leaf extract, dose-dependently inhibited the endogenous 26S
proteasome activity in MDA-MB-231 cells. Reduction in tumor growth was associated with a
decrease in proteasomal enzyme activities in the treated groups. Increased caspase-3 activity and
TUNEL-positive cells indicated enhanced apoptosis with Murraya leaf extract treatment.
Decreased expression of angiogenic and anti-apoptotic gene markers is indicative of inhibition of angiogenesis and
promotion of apoptosis in the leaf extract treated tumors.
