4′-Demethyl-deoxypodophyllotoxin glucoside isolated from Podophyllum hexandrum exhibits potential anticancer activities by altering Chk-2 signaling pathway in MCF-7 breast cancer cells

• Compounds (1–9) isolated from Podophyllum hexandrum exhibited cytotoxic potential.
• Compound 5 altering Chk-2 signaling pathway in MCF-7 breast cancer cells.
• Compound 5 was extensively studies first time with antiproliferative and ROS activity.

We investigated the root of Podophyllum hexandrum as a potential source of lead bioactive metabolites with anticancer activity. The present study led to the isolation of six known aryltetralin-type lignans designated as 4′-demethyl-deoxypodophyllotoxin (1), podophyllotoxin (2), 4′-demethyl-podophyllotoxin (3), podophyllotoxin-4-O-β-d-glucopyranoside (4), 4′-demethyl-deoxypodophyllotoxin-4-O-β-d-glucopyranoside (5), 4′-demethyl-podophyllotoxin-4-O-β-d-glucopyranoside (6), along with three known flavones Kaempferol (7), Quercetin (8), Astragalin (9) from the root of P. hexandrum. Compounds (1–9) exhibited the remarkable cytotoxic potential in diverse cancer cell lines. 5 therapeutic potential was extensively studied first time which exhibiting antiproliferative and ROS generating activity than its non-glycoside analogue 1. Furthermore, 5 augmented the apoptotic cascades in MCF-7 breast cancer cells, viz. nuclear condensation, membrane blebbing, probably by destabilizing the micro-tubular protein tubulin. Strikingly, our docking study and in vitro assays demonstrate that 5 binds to and modulate checkpoint kinase-2, a key cell cycle regulatory protein in normal and cancer cells.

Compound 5 binds to and modulates checkpoint kinase-2, thereby inducing apoptosis through mitotic catastrophe and G2/M cell cycle arrest in MCF-7 cells.Figure optionsDownload as PowerPoint slide