The biological activity of curcumin (CUR), a promising naturally occurring dietary compound for the treatment of hepatocellular carcinoma (HCC), was closely associated with its metabolite. Octahydrocurcumin (OHC) is the final hydrogenated metabolite of CUR and has been reported to have potential biological activities. However, difficulties in access have hampered its biological studies. In the current investigation, we designed an efficient synthesis method to produce OHC, and comparatively explored the anti-cancer effect and potential mechanism of OHC and CUR in an H22 ascites tumor-bearing mice model. The results indicated that OHC had a relatively wide margin of safety, and exhibited superior effects to CUR in suppressing the tumor growth, including ascending weight, abdominal circumference, ascites volume and cancer cell viability. OHC significantly induced H22 cell apoptosis by upregulating the p53 expression and downregulating the MDM2 expression. OHC also remarkably decreased the Bcl-2 and Bcl-xl protein expressions, and increased the Bax and Bad expressions in ascitic cells. Furthermore, THC substantially induced the release of cytochrome C, caspase-3, caspase-9 and the cleavage of PARP to induce H22 cell apoptosis. Taken together, OHC was more effective than CUR in suppressing H22-induced HCC through the activation of the mitochondrial apoptosis pathway. OHC may thus be a promising anti-HCC agent.

中文翻译：

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八氢姜黄素是姜黄素的最终氢化产物，通过诱导细胞凋亡而具有卓越的抗肿瘤活性†

姜黄素（CUR）的生物活性是一种有前途的天然饮食疗法，可用于治疗肝细胞癌（HCC），其生物活性与其代谢物密切相关。八氢姜黄素（OHC）是CUR的最终氢化代谢物，据报道具有潜在的生物活性。但是，获取方面的困难阻碍了它的生物学研究。在当前的研究中，我们设计了一种有效的合成OHC的方法，并在H22腹水荷瘤小鼠模型中比较探讨了OHC和CUR的抗癌作用及其潜在机制。结果表明，OHC具有相对较宽的安全范围，并且在抑制肿瘤生长方面表现出优于CUR的效果，包括增加体重，腹围，腹水量和癌细胞生存力。OHC通过上调p53表达和下调MDM2表达来显着诱导H22细胞凋亡。OHC还显着降低了腹水细胞中Bcl-2和Bcl-xl蛋白的表达，并增加了Bax和Bad的表达。此外，THC实质上诱导了细胞色素C，caspase-3，caspase-9的释放以及PARP的裂解，从而诱导H22细胞凋亡。两者合计，OHC比CUR通过激活线粒体凋亡途径抑制H22诱导的HCC更有效。因此，OHC可能是有前途的抗HCC药物。THC实质上诱导了细胞色素C，caspase-3，caspase-9的释放以及PARP的裂解，从而诱导H22细胞凋亡。两者合计，OHC比CUR通过激活线粒体凋亡途径抑制H22诱导的HCC更有效。因此，OHC可能是有前途的抗HCC药物。THC实质上诱导了细胞色素C，caspase-3，caspase-9的释放以及PARP的裂解，从而诱导H22细胞凋亡。两者合计，OHC比CUR通过激活线粒体凋亡途径抑制H22诱导的HCC更有效。因此，OHC可能是有前途的抗HCC药物。