title: Deoxypodophyllotoxin isolated from Juniperus communis induces apoptosis in breast cancer cells.
abstract: The study of anticancer properties from natural products has regained popularity as natural molecules provide a high diversity of chemical structures with specific biological and medicinal activity. Based on a documented library of the most common medicinal plants used by the indigenous people of North America, we screened and isolated compounds with anti-breast cancer properties from Juniperus communis (common Juniper). Using bioassay-guided fractionation of a crude plant extract, we identified the diterpene isocupressic acid and the aryltetralin lignan deoxypodophyllotoxin (DPT) as potent inducers of caspase-dependent programmed cell death (apoptosis) in malignant MB231 breast cancer cells. Further elucidation revealed that DPT, in contrast to isocupressic acid, also concomitantly inhibited cell survival pathways mediated by the MAPK/ERK and NFκB signaling pathways within hours of treatment. Our findings emphasize the potential and importance of natural product screening for new chemical entities with novel anticancer activities. Natural products research complemented with the wealth of information available through the ethnobotanical and ethnopharmacological knowledge of the indigenous peoples of North America can provide new candidate entities with desirable bioactivities to develop new cancer therapies.
authors.forename: Sami
authors.initials: S
authors.lastname: Benzina
authors.forename: Jason
authors.initials: J
authors.lastname: Harquail
authors.forename: Stephanie
authors.initials: S
authors.lastname: Jean
authors.forename: Annie-Pier
authors.initials: AP
authors.lastname: Beauregard
authors.forename: Caitlyn D
authors.initials: CD
authors.lastname: Colquhoun
authors.forename: Madison
authors.initials: M
authors.lastname: Carroll
authors.forename: Allyson
authors.initials: A
authors.lastname: Bos
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Gray
authors.affiliation: Universite de Moncton, Moncton, NB, Canada, E1A3E9. gilles.robichaud@umoncton.ca.
authors.forename: Gilles A
authors.initials: GA
authors.lastname: Robichaud
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002264:Carboxylic Acids / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000494:pharmacology; D004365:Drugs, Chinese Herbal; D005260:Female; D006801:Humans; D018653:Juniperus / Q000737:chemistry*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001688:Biological Products; D002264:Carboxylic Acids; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D010936:Plant Extracts; D013764:Tetrahydronaphthalenes; C110793:isocupressic acid; C014451:deoxypodophyllotoxin; D020929:Mitogen-Activated Protein Kinase Kinases; D020169:Caspases; D011034:Podophyllotoxin