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.

双类黄酮分为两类：以二聚体金黄色素类化合物为代表的C–C型化合物和以乙酰基黄酮（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。双黄酮醚的此后一个子组包括HNK，那黄酮，地卡那黄酮和一些其他二聚化合物，它们存在于多种植物中，特别是卷柏种类。提供了对HNK的抗癌特性和作用机理的全面综述，以强调HNK及其衍生物和含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基质金属蛋白酶MMP-2和MMP-9表达的调节（可能直接结合MMP-9） 。此外，发现HNK可以作为pre-mRNA剪接的有效调节剂，抑制SUMO特异性蛋白酶SENP1。因此，HNK代表一种罕见的天然SENP1抑制剂，也是设计合成化合物的支架。已经详细阐述了HNK的口服制剂，以增强其溶解度，促进化合物递送并增强其抗癌功效。该综述揭示了C–OC–C型双黄酮类化合物的抗癌潜力，尤其是HNK的药理作用。该化合物作为mRNA前剪接的调节剂值得进一步关注，可用于治疗癌症（尤其是肝细胞癌）和其他人类疾病。