Panobinostat (LBH589) is a potent, orally active, broad-spectrum histone deacetylase (HDAC) inhibitor with antitumor activity, exhibiting an IC50 value of 5nM[1]. Panobinostat induces hyperacetylation of histones and other intracellular proteins, allowing the expression of previously suppressed genes, thereby inhibiting cell proliferation and inducing apoptosis in malignant cells[2]. Panobinostat is commonly used in the treatment and research of diseases such as acute myeloid leukemia (AML), multiple myeloma (MM), Hodgkin's lymphoma (HL), and cutaneous T-cell lymphoma (CTCL)[3].
In vitro, treatment of small cell lung cancer (SCLC) H69 cells with panobinostat (20nM) alone for 60h resulted in >70% cell death, accompanied by an increase in the proportion of sub-G1 phase cells[4]. Treatment of various human and mouse melanoma cell lines (e.g., B16, WM793, and WM983A) with panobinostat (12.5-100nM) for 72h effectively inhibited cell growth, with IC50 values ranging from 25 to 100nM, while showing no effect on the growth of untransformed normal melanocytes[5]. Panobinostat (20nM) treatment of HUT78 and HH cells for 24h significantly induced caspase-3/7 activation, with an EC50 value of approximately 10nM[6].
In vivo, intravenous administration of panobinostat (7.5 or 15mg/kg/day; 5 days/week) for 2 weeks in CB.17 SCID mice bearing HH cell CTCL xenografts induced significant tumor regression (41% and 94%, respectively) and prolonged survival time[6]. Intraperitoneal injection of panobinostat (20mg/kg; 3 times/week) for 7 weeks in female nude mice inoculated with MDA-MB-231 cells significantly suppressed tumor volume growth, upregulated APCL gene expression in tumor xenografts, and downregulated β-catenin expression[7].
References:
[1] SCUTO A, KIRSCHBAUM M, KOWOLIK C, et al. The novel histone deacetylase inhibitor, LBH589, induces expression of DNA damage response genes and apoptosis in Ph- acute lymphoblastic leukemia cells[J]. Blood, 2008, 111(10): 5093-5100.
[2] ANNE M, SAMMARTINO D, BARGINEAR M F, et al. Profile of panobinostat and its potential for treatment in solid tumors: an update[J]. OncoTargets and Therapy, 2013, 6: 1613-1624.
[3] PRINCE H M, BISHTON M J, JOHNSTONE R W. Panobinostat (LBH589): a potent pan-deacetylase inhibitor with promising activity against hematologic and solid tumors[J]. Future Oncology, 2009, 5(5): 601-612.
[4] CRISANTI M C, WALLACE A F, KAPOOR V, et al. The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cells in vitro and in vivo with particular efficacy for small cell lung cancer[J]. Molecular Cancer Therapeutics, 2009, 8(8): 2221-2231.
[5] WOODS D M, WOAN K, CHENG F, et al. The antimelanoma activity of the histone deacetylase inhibitor panobinostat (LBH589) is mediated by direct tumor cytotoxicity and increased tumor immunogenicity[J]. Melanoma Research, 2013, 23(5): 341-348.
[6] SHAO W, GROWNEY J D, FENG Y, et al. Activity of deacetylase inhibitor panobinostat (LBH589) in cutaneous T-cell lymphoma models: defining molecular mechanisms of resistance[J]. International Journal of Cancer, 2010, 127(9): 2199-2208.
[7] QIN G, LI Y, XU X D, et al. Panobinostat (LBH589) inhibits Wnt/β-catenin signaling pathway via upregulating APCL expression in breast cancer[J]. Cellular Signalling, 2019, 59: 62-75.
Panobinostat (LBH589)是一种强效，且具有口服活性和抗肿瘤活性的广谱组蛋白去乙酰化酶（HDAC）抑制剂，IC50值为5nM[1]。Panobinostat可使组蛋白和其他细胞内蛋白过度乙酰化，允许表达原本受到抑制的基因，从而抑制细胞增殖和诱导恶性细胞凋亡[2]。Panobinostat通常用于急性髓系白血病 (AML)、多发性骨髓瘤 (MM)、霍奇金淋巴瘤 (HL)和皮肤 T 细胞淋巴瘤（CTCL）等疾病的治疗和研究[3]。
在体外，panobinostat（20nM）单独处理小细胞肺癌（SCLC）H69细胞60h，导致>70%细胞无法存活，并伴随sub-G1期细胞的比例增加[4]。Panobinostat（12.5-100nM）处理多种人和小鼠黑色素瘤细胞系（B16、WM793和WM983A等）72h，能有效抑制细胞生长，IC50值为25-100nM，且对未转化的正常黑色素细胞生长无影响[5]。Panobinostat（20nM）处理HUT78和HH细胞24h，显著诱导了caspase-3/7活化，EC50值约为10nM[6]。
在体内，panobinostat（7.5或15mg/kg/day; 5 days/week）通过静脉注射治疗携带HH细胞 CTCL异种移植瘤的CB.17 SCID小鼠2周，可诱导肿瘤的显著消退（分别为41%和94%），并延长小鼠的生存时间[6]。Panobinostat（20mg/kg; 3 times/week）通过腹腔注射治疗接种了MDA-MB-231细胞的雌性裸鼠7周，能显著抑制肿瘤体积的增长，并上调肿瘤异种移植组织中APCL基因的表达，同时下调β-catenin的表达[7]。