Title:Phomoxanthone A - From Mangrove Forests to Anticancer Therapy
Volume: 22
Issue: 30
Author(s): Marian Frank, Hendrik Niemann, Philip Böhler, Björn Stork, Sebastian Wesselborg, Wenhan Lin and Peter Proksch
Affiliation:
Keywords:
Anticancer therapy, apoptosis, atropisomerism, endophytic fungi, immunostimulation, mangroves,
polyketide, tetrahydroxanthone.
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.
