Ganoderic acids suppress growth and invasive behavior of breast cancer cells by modulating AP-1 and NF-kappaB signaling.
Structurally related lanostane-type triterpenes, ganoderic acid A, F and H (GA-A, GA-F, GA-H), were identified in an oriental medicinal mushroom Ganoderma lucidum. In the present study we evaluated the effect of GA-A, GA-H and GA-F on highly invasive human breast cancer cells. We showed that GA-A and GA-H suppressed growth (cell proliferation and colony formation) and invasive behavior (adhesion, migration and invasion) of MDA-MB-231 cells. Our results suggest that GA-A and GA-H mediate their biological effects through the inhibition of transcription factors AP-1 and NF-kappaB, resulting in the down-regulation of expression of Cdk4 and the suppression of secretion of uPA, respectively. Furthermore, the activity of ganoderic acids is linked to the hydroxylation in the position 7 and 15 (GA-A) and 3 (GA-H) in their triterpene lanostane structure. In conclusion, hydroxylated triterpenes from G. lucidum could be promising natural agents for the therapy of invasive breast cancers.
Jiang
Jiahua
J
Cancer Research Laboratory, Methodist Research Institute, Indianapolis, IN 46202, USA.
Grieb
Brian
B
Thyagarajan
Anita
A
Sliva
Daniel
D
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects*; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D005260:Female; D006538:Heptanoic Acids / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism*; D020940:Reishi / Q000737:chemistry; D015398:Signal Transduction / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D000970:Antineoplastic Agents; D006538:Heptanoic Acids; D016328:NF-kappa B; D018808:Transcription Factor AP-1; C515007:ganoderic acid H; D007810:Lanosterol; C515005:ganoderic acid A; C515006:ganoderic acid F; D051358:Cyclin-Dependent Kinase 4; D014568:Urokinase-Type Plasminogen Activator