2. Academic Validation
  3. 4'-Demethyl-deoxypodophyllotoxin glucoside isolated from Podophyllum hexandrum exhibits potential anticancer activities by altering Chk-2 signaling pathway in MCF-7 breast cancer cells

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

  • Chem Biol Interact. 2014 Dec 5;224:100-7. doi: 10.1016/j.cbi.2014.09.022.
Mahesh K Zilla 1,  Debasis Nayak 2,  Hina Amin 3,  Yedukondalu Nalli 1,  Bilal Rah 2,  Souneek Chakraborty 2,  Surender Kitchlu 4,  Anindya Goswami 5,  Asif Ali 6
Affiliations

Affiliations

  • 1 Academy of Scientific and Innovative Research, New Delhi, India; Natural Product Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
  • 2 Academy of Scientific and Innovative Research, New Delhi, India; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
  • 3 Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
  • 4 Biodiversity and Applied Botany Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
  • 5 Academy of Scientific and Innovative Research, New Delhi, India; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India. Electronic address: agoswami@iiim.ac.in.
  • 6 Academy of Scientific and Innovative Research, New Delhi, India; Natural Product Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India. Electronic address: asifali@iiim.ac.in.
PMID: 25446499 DOI: 10.1016/j.cbi.2014.09.022
Abstract

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.

Keywords

Breast cancer; Chk2; Cytotoxicity; G2/M arrest; Podophyllum hexandrum.

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