Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara P.O., Kochi, Kerala, 682041, India.
Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara P.O., Kochi, Kerala, 682041, India.
Naunyn Schmiedebergs Arch Pharmacol. 2023 Oct;396(10):2461-2467. doi: 10.1007/s00210-023-02468-8. Epub 2023 Mar 29.
Phytochemicals have been promising candidates for cancer therapy, affecting various cancer initiation and progression stages. Kaempferide is a mono methoxy flavone that shows potent anticancer effects on multiple cancers both in vitro and in vivo.
We evaluated the anticancer activity of kaempferide against HCC using an MTT ((3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. HepG2, Huh7, and N1S1 were used for preliminary in vitro studies. This is followed by an apoptosis analysis assessed by caspase-3 and 9. The in vivo effects of the compound were studied in the N1S1 orthotopically injected SD (Sprague Dawley) rat model, where the animal was given kaempferide (25 mg/kg thrice a week) and vehicle (Cremophor:ethanol) iv. The expression of caspase-9 and a critical tumor marker, transforming growth factor beta 1 (TGF-β 1), were assessed in both control and treatment tumor samples.
Kaempferide-induced dose-dependent cytotoxicity in three HCC cell lines (HepG2: IC50 = 27.94 ± 2.199 µM; Huh7: IC50 = 25.65 ± 0.956 µM; and N1S1: IC50 = 15.18 ± 3.68 µM). Furthermore, caspase-dependent apoptosis was confirmed in vitro. Kaempferide showed a significant reduction in tumor size and tumor volume in vivo. Histopathological evaluation by hematoxylin and eosin (H&E) staining confirmed that altered cells were significantly demolished in the kaempferide-treated animals, which correlates with tumor reduction compared to the vehicle-treated group. Caspase-9 levels were also found to be increased in the treatment group. TGF-β 1, a crucial marker in invasion and metastasis of liver cancer, was also downregulated in the treatment group (control = 207.8 ± 22.9 pg/mL and kaempferide-treated = 157.3 ± 13.8 pg/mL).
We report for the first time the potential of kaempferide as a promising alternative against HCC, which further warrants its clinical validation.
植物化学物质一直是癌症治疗的有前途的候选物，可影响癌症的多个起始和进展阶段。山奈酚是一种单甲氧基黄酮，在体外和体内对多种癌症均具有很强的抗癌作用。
我们使用 MTT（（3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四唑溴盐）测定法评估了山奈酚对 HCC 的抗癌活性。HepG2、Huh7 和 N1S1 用于初步的体外研究。然后通过 caspase-3 和 9 评估凋亡分析。在 N1S1 原位注射 SD（Sprague Dawley）大鼠模型中研究了该化合物的体内作用，其中动物每周三次接受 25mg/kg 的山奈酚和载体（Cremophor：乙醇）iv 治疗。在对照和治疗肿瘤样本中评估了 caspase-9 和关键肿瘤标志物转化生长因子β 1（TGF-β 1）的表达。
山奈酚在三种 HCC 细胞系（HepG2：IC50=27.94±2.199μM；Huh7：IC50=25.65±0.956μM；和 N1S1：IC50=15.18±3.68μM）中诱导了剂量依赖性细胞毒性。此外，还在体外证实了 caspase 依赖性细胞凋亡。山奈酚在体内显著减小了肿瘤的大小和体积。苏木精和伊红（H&E）染色的组织病理学评估证实，与对照组相比，在山奈酚治疗的动物中，改变的细胞明显被破坏，这与肿瘤减少有关。还发现治疗组中的 caspase-9 水平升高。转化生长因子β 1（TGF-β 1）是肝癌侵袭和转移的关键标志物，在治疗组中也下调（对照组=207.8±22.9pg/mL 和山奈酚治疗组=157.3±13.8pg/mL）。
我们首次报道了山奈酚作为 HCC 有前途的替代药物的潜力，这进一步证明了其临床验证的必要性。
