Pladienolide B

Pladienolide B is a potent cancer cell growth inhibitor that targets the SF3B1 subunit of the spliceosome. Pladienolide B exerts antitumor activities mediated through the inhibition of pre-mRNA splicing. Pladienolide B induces apoptosis[1][2][3].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Pladienolide B (0.1-2 nM; 24-72 hours) inhibits human cervical carcinoma cells viability[3]. Pladienolide B (0.1-2 nM; 24-48 hours) reduces SF3b1 expression in human cervical carcinoma cells[3]. Pladienolide B induces (0.1-2 nM; 24 hours) cell cycle arrest and apoptosis[3]. Cell Viability Assay[3] Cell Line: HeLa cells Concentration: 0.1, 0.5, 1, 1.5, 2 nM Incubation Time: 24, 48, 72 hours Result: Significantly decreased cell viability, and the decrease was concentration- and time-dependent. Apoptosis Analysis[3] Cell Line: HeLa cells Concentration: 0.1, 0.5, and 2 nM Incubation Time: 24 hours Result: The apoptotic cells were highly induced at 24 hours. RT-PCR[3] Cell Line: HeLa cells Concentration: 0.1, 0.5, and 2 nM Incubation Time: 24, 48 hours Result: Induced a time- and concentration-dependent decrease in cellular SF3b1 proteins.

Pladienolide B (2.5-10 mg/kg; i.v.; daily for 5 days) has strong antitumor activities[4]. Animal Model: Female or male BALB/c nu/nu mice (7 weeks of age) (PC-3, OVCAR-3, DU-145, WiDr, and HCT-116, BSY-1 xenografts)[4] Dosage: 2.5, 5, and 10 mg/kg Administration: I.v.; daily for 5 days Result: Showed strong growth inhibitory or regressive activities against these xenografts.

[1]. Effenberger KA, et al. Coherence between cellular responses and in vitro splicing inhibition for the anti-tumor drug pladienolide B and its analogs. J Biol Chem. 2014 Jan 24;289(4):1938-47.

[2]. Aouida M, et al. CRISPR/Cas9-mediated target validation of the splicing inhibitor Pladienolide B. Biochim Open. 2016 Feb 24;3:72-75.

[3]. Zhang Q, et al. Inhibition of SF3b1 by pladienolide B evokes cycle arrest, apoptosis induction and p73 splicing in human cervical carcinoma cells. Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):1273-1280.

[4]. Mizui Y, et al. Pladienolides, new substances from culture of Streptomyces platensis Mer-11107. III. In vitro and in vivo antitumor activities. J Antibiot (Tokyo). 2004 Mar;57(3):188-96.