title: Phomoxanthone A--From Mangrove Forests to Anticancer Therapy.
abstract: Mangrove associated endophytes are treasure chests for bioprospecting especially in light of the need for new anticancer leads that are necessary to overcome drug resistance of cancer cells. This review highlights the potent anti-tumour compound phomoxanthone A (PXA), which represents a tetrahydroxanthone atropisomer derived from the mangrove-associated fungus Phomopsis longicolla. PXA displayed strong anti-tumour activity when tested against a panel of solid (including cisplatin resistant) tumour cell lines or of blood cancer cell lines with IC50 values in the submicromolar range whereas it was up to 100 folds less active against peripheral blood mononuclear cells (PBMC) from healthy donors. The anti-tumour activity of PXA was demonstrated to be due to an induction of caspase 3 dependent apoptosis. At the same time PXA was shown to activate immune cells such as murine T-lymphocytes, NK cells and macrophages which might help in fighting resistance during cancer chemotherapy. Structure activity studies that involved several naturally occurring as well as semisynthetic derivatives of PXA indicated the position of the biaryl linkage and the acetyl substituents as structural features that are important for the activity of this natural product.
authors.forename: Marian
authors.initials: M
authors.lastname: Frank
authors.forename: Hendrik
authors.initials: H
authors.lastname: Niemann
authors.forename: Philip
authors.initials: P
authors.lastname: Böhler
authors.forename: Björn
authors.initials: B
authors.lastname: Stork
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wesselborg
authors.forename: Wenhan
authors.initials: W
authors.lastname: Lin
authors.affiliation: Department of Pharmaceutical Biology and Biotechnology, Faculty of Pharmacy, Heinrich- Heine University, 40225 Duesseldorf, Germany. proksch@uni-duesseldorf.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Proksch
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects; D005658:Fungi / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D053833:Wetlands; D044004:Xanthones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D016588:Anticarcinogenic Agents; D044004:Xanthones; C436332:phomoxanthone A