Bioactivity Programme, Natural Products Division, Forest Research Institute Malaysia, Kepong 52109, Malaysia.
Phytochemistry Programme, Natural Products Division, Forest Research Institute Malaysia, Kepong 52109, Malaysia.
Molecules. 2022 Jan 18;27(3):585. doi: 10.3390/molecules27030585.
An alkaloid compound from the hairy root culture of has been isolated and characterised as 9-methoxycanthin-6-one. The aims of these studies were to investigate the in vitro anti-cancer activities of 9-methoxycanthin-6-one against ovarian cancer (A2780, SKOV-3), breast cancer (MCF-7), colorectal cancer (HT29), skin cancer (A375) and cervical cancer (HeLa) cell lines by using a Sulphorhodamine B assay, and to evaluate the mechanisms of action of 9-methoxycanthin-6-one via the Hoechst 33342 assay and proteomics approach. The results had shown that 9-methoxycanthin-6-one gave IC values of 4.04 ± 0.36 µM, 5.80 ± 0.40 µM, 15.09 ± 0.99 µM, 3.79 ± 0.069 µM, 5.71 ± 0.20 µM and 4.30 ± 0.27 µM when tested in A2780, SKOV-3, MCF-7, HT-29, A375 and HeLa cell lines, respectively. It was found that 9-methoxycanthin-6-one induced apoptosis in a concentration dependent manner when analysed via the Hoechst 33342 assay. 9-methoxycanthine-6-one were found to affect the expressions of apoptotic-related proteins, that were proteins pyruvate kinase (PKM), annexin A2 (ANXA2), galectin 3 (LGAL3), heterogeneous nuclear ribonucleoprotein A1 (HNRNP1A1), peroxiredoxin 3 (PRDX3), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from the differential analysis of 2-DE profiles between treated and non-treated 9-methoxycanthine-6-one. Proteins such as acetyl-CoA acyltransferase 2 (ACAA2), aldehyde dehydrogenase 1 (ALDH1A1), capping protein (CAPG), eukaryotic translation elongation factor 1 (EEF1A1), malate dehydrogenase 2 (MDH2), purine nucleoside phosphorylase (PNP), and triosephosphate isomerase 1 (TPI1) were also identified to be associated with A2780 cell death induced by 9-methoxycanthine-6-one. These findings may provide a new insight on the mechanisms of action of 9-methoxycanthin-6-one in exerting its anti-cancer effects in vitro.
从 的发根培养物中分离得到一种生物碱化合物，并鉴定为 9-甲氧基卡亭-6-酮。这些研究的目的是通过磺酰罗丹明 B 测定法研究 9-甲氧基卡亭-6-酮对卵巢癌（A2780、SKOV-3）、乳腺癌（MCF-7）、结直肠癌（HT29）、皮肤癌（A375）和宫颈癌（HeLa）细胞系的体外抗癌活性，并通过 Hoechst 33342 测定法和蛋白质组学方法评估 9-甲氧基卡亭-6-酮的作用机制。结果表明，9-甲氧基卡亭-6-酮在 A2780、SKOV-3、MCF-7、HT-29、A375 和 HeLa 细胞系中的 IC 值分别为 4.04±0.36µM、5.80±0.40µM、15.09±0.99µM、3.79±0.069µM、5.71±0.20µM 和 4.30±0.27µM。通过 Hoechst 33342 分析发现，9-甲氧基卡亭-6-酮以浓度依赖的方式诱导细胞凋亡。在差异分析中发现，9-甲氧基卡亭-6-酮处理和未处理的 9-甲氧基卡亭-6-酮之间的 2-DE 图谱，9-甲氧基卡亭-6-酮影响凋亡相关蛋白的表达，这些蛋白包括丙酮酸激酶（PKM）、膜联蛋白 A2（ANXA2）、半乳糖凝集素 3（LGAL3）、异质核核糖核蛋白 A1（HNRNP1A1）、过氧化物酶 3（PRDX3）和甘油醛-3-磷酸脱氢酶（GAPDH）。还鉴定出乙酰辅酶 A 酰基转移酶 2（ACAA2）、醛脱氢酶 1（ALDH1A1）、帽蛋白（CAPG）、真核翻译延伸因子 1（EEF1A1）、苹果酸脱氢酶 2（MDH2）、嘌呤核苷磷酸化酶（PNP）和磷酸丙糖异构酶 1（TPI1）等蛋白与 9-甲氧基卡亭-6-酮诱导的 A2780 细胞死亡有关。这些发现可能为 9-甲氧基卡亭-6-酮在体外发挥抗癌作用的作用机制提供新的见解。
