Falcarinol is a naturally derived, orally active Hsp90 inhibitor [1]. Falcarinol binds to both the N- and C-terminal ATP-binding sites of Hsp90, inducing apoptosis in non-small cell lung cancer (NSCLC) and its cancer stem cell populations by disrupting Hsp90 function without upregulating Hsp70 [1-2]. Falcarinol is primarily used in inflammatory models and for colorectal cancer prevention research [3-4].
In Caco-2 cells, Falcarinol (0.001-20μg/mL; 72h) treatment significantly reduced cell proliferation under basal growth conditions [5]. In Caco-2 cells, Falcarinol (0.5-100μM; 24h, 72h) decreased expression of the apoptosis indicator caspase-3 concomitantly with decreased basal DNA strand breakage [6]. In PANC-1 cells, after treatment with Falcarinol (0.5μg/mL; 72h), most cells detached and showed signs of cell death [7].
In CB57BL/6 mice, Falcarinol (5mg/kg; po; 8d) pretreatment effectively reduced the expression levels of intestinal pro-inflammatory genes [8]. In endotoxin-induced acute inflammation mice model, Falcarinol (5mg/kg; po; 7d) pretreatment leads to a unique Th2/Th9 plasma cytokine imbalance and robust induction of Ho1 at the intestinal mRNA and protein levels [9].
References:
[1]. Le H T, Nguyen H T, Min H Y, et al. Panaxynol, a natural Hsp90 inhibitor, effectively targets both lung cancer stem and non-stem cells[J]. Cancer Letters, 2018, 412: 297-307.
[2]. Gonçalves E C D, Baldasso G M, Bicca M A, et al. Terpenoids, cannabimimetic ligands, beyond the cannabis plant[J]. Molecules, 2020, 25(7): 1567.
[3]. Kobaek-Larsen M, Baatrup G, K. Notabi M, et al. Dietary polyacetylenic oxylipins falcarinol and falcarindiol prevent inflammation and colorectal neoplastic transformation: A mechanistic and dose-response study in a rat model[J]. Nutrients, 2019, 11(9): 2223.
[4]. Christensen L P, Larsen M K, El-Houri R, et al. Polyacetylenes of the falcarinol type: A promising new class of neutraceuticals and lead compounds for the development of anticancer drugs[J]. 2017.
[5]. Purup S, Larsen E, Christensen L P. Differential effects of falcarinol and related aliphatic C17-polyacetylenes on intestinal cell proliferation[J]. Journal of agricultural and food chemistry, 2009, 57(18): 8290-8296.
[6]. Young J F, Duthie S J, Milne L, et al. Biphasic effect of falcarinol on CaCo-2 cell proliferation, DNA damage, and apoptosis[J]. Journal of Agricultural and Food Chemistry, 2007, 55(3): 618-623.
[7]. Cheung S S C, Hasman D, Khelifi D, et al. Devil’s Club falcarinol-type polyacetylenes inhibit pancreatic cancer cell proliferation[J]. Nutrition and Cancer, 2019, 71(2): 301-311.
[8]. Stefanson A L, Bakovic M. Falcarinol Is a Potent Inducer of Heme Oxygenase‐1 and Was More Effective than Sulforaphane in Attenuating Intestinal Inflammation at Diet‐Achievable Doses[J]. Oxidative Medicine and Cellular Longevity, 2018, 2018(1): 3153527.
[9]. Stefanson A, Bakovic M. Dietary polyacetylene falcarinol upregulated intestinal heme oxygenase-1 and modified plasma cytokine profile in late phase lipopolysaccharide-induced acute inflammation in CB57BL/6 mice[J]. Nutrition Research, 2020, 80: 89-105.
Falcarinol是一种天然来源的口服Hsp90抑制剂 [1]。Falcarinol可与Hsp90的N端和C端ATP结合位点结合，通过破坏Hsp90的功能而不上调Hsp70的表达，诱导非小细胞肺癌（NSCLC）及其肿瘤干细胞群凋亡 [1-2]。Falcarinol主要用于炎症模型和结直肠癌预防研究 [3-4]。
在Caco-2细胞中，Falcarinol（0.001-20μg/mL；72h）处理可显著降低基础生长条件下的细胞增殖 [5]。在Caco-2细胞中，Falcarinol（0.5-100μM；24h，72h）可降低凋亡指标caspase-3的表达，同时减少基础DNA链断裂 [6]。在PANC-1细胞中，用Falcarinol（0.5μg/mL；72h）处理后，大多数细胞脱落并出现细胞死亡迹象 [7]。
在CB57BL/6小鼠中，Falcarinol（5mg/kg；po；8d）预处理有效降低了肠道促炎基因的表达水平 [8]。在内毒素诱导的急性炎症小鼠模型中，Falcarinol（5mg/kg；po；7d）预处理导致独特的Th2/Th9血浆细胞因子失衡，并在肠道mRNA和蛋白质水平上强烈诱导Ho1 [9]。