title: Anticancer effect of altersolanol A, a metabolite produced by the endophytic fungus Stemphylium globuliferum, mediated by its pro-apoptotic and anti-invasive potential via the inhibition of NF-κB activity.
abstract: Altersolanol A, a natural product from the endophytic fungus Stemphylium globuliferum isolated from the medicinal plant Mentha pulegium (Lamiaceae) growing in Morocco, shows cytotoxic, cytostatic, anti-inflammatory and anti-migrative activity against human chronic myeloid K562 leukemia and A549 lung cancer cells in a dose dependent manner without affecting the viability of non cancerous cells. Altersolanol A induces cell death by apoptosis through the cleavage of caspase-3 and -9 and through the decrease of anti-apoptotic protein expression. Moreover, we report here the importance of the distinct structural features of altersolanol A by testing other related anthracene derivatives in order to identify preliminary structure-activity relationships. Acetylation of altersolanol A did not improve activity where other derivatives such as tetrahydroaltersolanol B and ampelanol that differ from altersolanol A by reduction of one of a carbonyl group and removal of hydroxyl substituents were inactive in comparison. Altogether our results suggest that altersolanol A may be considered as an interesting lead for further development of chemotherapeutic agents.
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, 9 Rue Edward Steichen, L-2540 Luxembourg, Luxembourg.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Teiten
authors.forename: Fabienne
authors.initials: F
authors.lastname: Mack
authors.forename: Abdessamad
authors.initials: A
authors.lastname: Debbab
authors.forename: Amal H
authors.initials: AH
authors.lastname: Aly
authors.forename: Mario
authors.initials: M
authors.lastname: Dicato
authors.forename: Peter
authors.initials: P
authors.lastname: Proksch
authors.forename: Marc
authors.initials: M
authors.lastname: Diederich
mesh_terms: D000880:Anthraquinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001203:Ascomycota / Q000737:chemistry; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D031335:Mentha pulegium / Q000382:microbiology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000880:Anthraquinones; D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C058812:altersolanol A