Biflavonoids are divided in two classes: C–C type compounds represented by the dimeric compound amentoflavone and C–O–C-type compounds typified by hinokiflavone (HNK) with an ether linkage between the two connected apigenin units. This later sub-group of bisflavonyl ethers includes HNK, ochnaflavone, delicaflavone and a few other dimeric compounds, found in a variety of plants, notably Selaginella species. A comprehensive review of the anticancer properties and mechanism of action of HNK is provided, to highlight the anti-proliferative and anti-metastatic activities of HNK and derivatives, and HNK-containing plant extracts. The anticancer effects rely on the capacity of HNK to interfere with the ERK1-2/p38/NFκB signaling pathway and the regulation of the expression of the matrix metalloproteinases MMP-2 and MMP-9 (with a potential direct binding to MMP-9). In addition, HNK was found to function as a potent modulator of pre-mRNA splicing, inhibiting the SUMO-specific protease SENP1. As such, HNK represents a rare SENP1 inhibitor of natural origin and a scaffold to design synthetic compounds. Oral formulations of HNK have been elaborated to enhance its solubility, to facilitate the compound delivery and to enhance its anticancer efficacy. The review shed light on the anticancer potential of C–O–C-type biflavonoids and specifically on the pharmacological profile of HNK. This compound deserves further attention as a regulator of pre-mRNA splicing, useful to treat cancers (in particular hepatocellular carcinoma) and other human pathologies.

双黄酮类化合物分为两类：以二聚化合物穗花果黄酮为代表的 C-C 型化合物和以扁柏黄酮 (HNK) 为代表的 C-O-C 型化合物，两个连接的芹菜素单元之间具有醚键。双黄酮醚的后来亚组包括 HNK、ochnaflavone、delicaflavone 和一些其他二聚化合物，在多种植物中发现，特别是卷柏物种。对 HNK 的抗癌特性和作用机制进行了全面综述，重点介绍了 HNK 及其衍生物以及含 HNK 的植物提取物的抗增殖和抗转移活性。抗癌作用依赖于 HNK 干扰 ERK1-2/p38/NFκB 信号通路的能力以及对基质金属蛋白酶 MMP-2 和 MMP-9 表达的调节（有可能直接与 MMP-9 结合） 。此外，HNK 被发现可作为前 mRNA 剪接的有效调节剂，抑制 SUMO 特异性蛋白酶 SENP1。因此，HNK 代表了一种罕见的天然 SENP1 抑制剂，也是设计合成化合物的支架。 HNK 的口服制剂经过精心设计，以提高其溶解度、促进化合物递送并增强其抗癌功效。该综述揭示了 C-O-C 型双黄酮类化合物的抗癌潜力，特别是 HNK 的药理学特征。这种化合物作为前 mRNA 剪接的调节剂值得进一步关注，可用于治疗癌症（特别是肝细胞癌）和其他人类病理。