Yang Huihai, Zheng Tao, Ku Chuen-Fai, Ngai Cheuk Kit, Yue Grace Gar-Lee, Lee Hung Kay, Lau Clara Bik-San
Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
Front Chem. 2023 Jun 2;11:1195883. doi: 10.3389/fchem.2023.1195883. eCollection 2023.
The plant Juss. (PV) has long been used as a medicinal herb for treating intestinal disorders. Pharmacological activities such as anti-oxidation, anti-inflammation, and anti-cancer effects of compounds isolated from PV have been reported, but these bioactive compounds were not derived from PV water extract (PVW). Therefore, in the present study, we aimed to identify the active component(s) of PVW which exhibit inhibitory activities in colon cancer cells viability and migration. Human colon cancer HCT116 cells were treated with the isolated compounds of PVW and then subjected to MTT and transwell migration assays. Our results showed that an active compound in PVW, 8,9-didehydro-7-hydroxydolichodial (DHD) inhibited cell viability of HCT116 cells, with IC value at 6.1 ± 2.2 μM. Interestingly, DHD was not detected in the herbal material of PV. Further investigation revealed that DHD is in fact a heat-generated compound derived from a natural compound present in PV, namely valerosidate. Valerosidate also reduced cell viability in HCT116 cells, with IC value at 22.2 ± 1.1 μM. Moreover, both DHD (2.75 μM) and valerosidate (10.81 μM) suppressed cell migration in HCT116 cells, with inhibitory rates at 74.8% and 74.6%, respectively. In addition, western blot results showed that DHD (5.5 μM) could significantly increase p53 expression by 34.8% and PTEN expression by 13.9%, while valerosidate (21.6 μM) could increase expressions of p53 and PTEN by 26.1% and 34.6%, respectively in HCT116 cells after 48 h treatment. Taken together, this is the first report that a naturally-occurring valerosidate present in PV could actually transform to DHD by thermal hydrolysis, and both compounds exhibited inhibitory effects on cell viability and migration in HCT116 cells via increasing the expressions of tumor suppressors (p53 and PTEN). Our findings demonstrated that valerosidate is present in raw herb PV but not in PVW, while DHD is present in PVW rather than in raw herb PV. This difference in chemical profiles of raw herb and boiled water extract of PV may affect the anti-cancer activity, and hence further investigations are warranted.
植物Juss.（PV）长期以来一直被用作治疗肠道疾病的草药。从PV中分离出的化合物具有抗氧化、抗炎和抗癌等药理活性，但这些生物活性化合物并非来自PV水提取物（PVW）。因此，在本研究中，我们旨在鉴定PVW中对结肠癌细胞活力和迁移具有抑制活性的活性成分。用PVW的分离化合物处理人结肠癌HCT116细胞，然后进行MTT和Transwell迁移试验。我们的结果表明，PVW中的一种活性化合物8,9-二脱氢-7-羟基多聚二醛（DHD）抑制HCT116细胞的活力，IC值为6.1±2.2μM。有趣的是，在PV的草药材料中未检测到DHD。进一步研究表明，DHD实际上是一种由PV中存在的天然化合物戊酸酯热生成的化合物。戊酸酯也降低了HCT116细胞的活力，IC值为22.2±1.1μM。此外，DHD（2.75μM）和戊酸酯（10.81μM）均抑制HCT116细胞的迁移，抑制率分别为74.8%和74.6%。此外，蛋白质印迹结果表明，DHD（5.5μM）可使p53表达显著增加34.8%，PTEN表达增加13.9%，而戊酸酯（21.6μM）在处理48小时后可使HCT116细胞中p53和PTEN的表达分别增加26.1%和34.6%。综上所述，这是首次报道PV中天然存在的戊酸酯可通过热水解转化为DHD，且两种化合物均通过增加肿瘤抑制因子（p53和PTEN）的表达对HCT116细胞的活力和迁移产生抑制作用。我们的研究结果表明，戊酸酯存在于生药PV中而不存在于PVW中，而DHD存在于PVW中而非生药PV中。PV生药和煮水提取物的化学特征差异可能会影响抗癌活性，因此有必要进一步研究。
