title: 4'-Demethyl-deoxypodophyllotoxin glucoside isolated from Podophyllum hexandrum exhibits potential anticancer activities by altering Chk-2 signaling pathway in MCF-7 breast cancer cells.
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.
authors.affiliation: Academy of Scientific and Innovative Research, New Delhi, India; Natural Product Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors.forename: Mahesh K
authors.initials: MK
authors.lastname: Zilla
authors.affiliation: Academy of Scientific and Innovative Research, New Delhi, India; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors.forename: Debasis
authors.initials: D
authors.lastname: Nayak
authors.affiliation: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors.forename: Hina
authors.initials: H
authors.lastname: Amin
authors.affiliation: Academy of Scientific and Innovative Research, New Delhi, India; Natural Product Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors.forename: Yedukondalu
authors.initials: Y
authors.lastname: Nalli
authors.affiliation: Academy of Scientific and Innovative Research, New Delhi, India; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors.forename: Bilal
authors.initials: B
authors.lastname: Rah
authors.affiliation: Academy of Scientific and Innovative Research, New Delhi, India; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors.forename: Souneek
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: Biodiversity and Applied Botany Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors.forename: Surender
authors.initials: S
authors.lastname: Kitchlu
authors.affiliation: 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.
authors.forename: Anindya
authors.initials: A
authors.lastname: Goswami
authors.affiliation: 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.
authors.forename: Asif
authors.initials: A
authors.lastname: Ali
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D064447:Checkpoint Kinase 2 / Q000378:metabolism*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005960:Glucosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D010766:Phosphorylation; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D011035:Podophyllum / Q000737:chemistry*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D050257:Tubulin Modulators / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: C000614156:4'-demethyldeoxypodophyllotoxin-4-O-glucopyranoside; D000972:Antineoplastic Agents, Phytogenic; D005960:Glucosides; D017382:Reactive Oxygen Species; D050257:Tubulin Modulators; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D051057:Proto-Oncogene Proteins c-akt; D011034:Podophyllotoxin
keywords: Breast cancer; Chk2; Cytotoxicity; G2/M arrest; Podophyllum hexandrum