Galiellalactone

Galiellalactone is a is a small non-toxic and non-mutagenic fungal metabolite, a selective inhibitor of STAT3 signaling, with an IC50 of 250-500 nM. Galiellalactone can be used to research castration-resistant prostate cancer[1][2][3].

Signaling Pathways >> Stem Cell/Wnt >> STAT

Research Areas >> Cancer

Signaling Pathways >> JAK/STAT Signaling >> STAT

STAT3:250-500 nM (IC50)

Galiellalactone (2.5-25 μM; 24-72 hour) induces apoptosis of prostate cancer (PCa) cell lines expressingp-Stat3[1]. Galiellalactone (2.5-25 μM; 24-72 hour) decreases viability of DU145 cells[1]. Galiellalactone (10 μM) inhibits STAT3 signaling activity as assessed by luciferase reporter gene assay in IL-6-stimulated LNCaP cells[2]. Galiellalactone (10-100 μM; 1 hour) binds directly to STAT3 in DU145 cells [2]. Galiellalactone (5-50 μM; 1 hour) interferes with STAT3 DNA binding without inhibiting phosphorylation in DU145 cells [2]. Apoptosis Analysis[1] Cell Line: DU145, PC-3, and LNCaP cells Concentration: 0, 2.5, 5, 10, 25 μM Incubation Time: 24, 48, 72 hours Result: Induced an apoptotic response in PC-3 and DU145 cells. Cell Viability Assay[1] Cell Line: DU145 cells Concentration: 0, 2.5, 5, 10, 17.5, 25 μM Incubation Time: 24, 48, 72 hours Result: Decreased DU145 cells viability in a dose- and time-dependent manner. Western Blot Analysis[1] Cell Line: DU145 cells Concentration: 0, 10, 25 μM Incubation Time: 48 hours Result: Induced expression of the apoptotic marker cleaved caspase-3 and increased expression of cleaved PARP. Western Blot Analysis[2] Cell Line: DU145 cells Concentration: 0, 10, 25, 50, 100 μM Incubation Time: 1 hour Result: Prevented the binding of the biotinylated analogue of galiellalactone (GL-biot) to STAT3 in a dose-dependent manner demonstrating competitive binding. Western Blot Analysis[2] Cell Line: DU145 cells Concentration: 0, 5, 10, 25, 50 μM Incubation Time: 1 hour Result: Inhibited STAT3 binding to DNA in a dose-dependent manner. Did not affect phosphorylation of STAT3 Tyr-705 and Ser-727 or the expression of total STAT3.

Galiellalactone (1, 3 mg/kg; daily i.p. for 3 weeks) inhibits PCa tumor growth in vivo[1]. Animal Model: Male nude NMR1 mice are injected PCa cell[1] Dosage: 0, 1, 3 mg/kg Administration: Daily i.p. injections for 3 weeks Result: Reduced the tumor growth rate in DU145 xenografts by 41-42% and was well tolerated.

[1]. Hellsten R, et, al. Galiellalactone is a novel therapeutic candidate against hormone-refractory prostate cancer expressing activated Stat3. Prostate. 2008 Feb 15; 68(3): 269-80.

[2]. Doncow DN, et, al. Galiellalactone is a direct inhibitor of the transcription factor STAT3 in prostate cancer cells. J Biol Chem. 2014 Jun 6; 289(23): 15969-78.

[3]. Weidler M, et, al. Inhibition of interleukin-6 signaling by galiellalactone. FEBS Lett. 2000 Oct 27; 484(1): 1-6.