Abstract：
BACKGROUND: The plants of Amaryllidaceae family, such as Amaryllis belladonna L., have been used as herbal remedies for thousands of years to address various disorders, including diseases that might today be identified as cancer.
OBJECTIVE: The objective of this work was to evaluate the potential of three Amaryllidaceae alkaloids against four cancer cell lines.
METHODS: The alkaloids lycorine, 1-O-acetylcaranine, and montanine were evaluated in vitro against colon adenocarcinoma cell line (HCT-116) and breast carcinoma cell lines (MCF-7, MDAMB231, and Hs578T). Computational experiments (target prediction and molecular docking) were conducted to gain a deeper comprehension of possible interactions between these alkaloids and potential targets associated with these tumor cells.
RESULTS: Montanine presented the best results against HCT-116, MDAMB231, and Hs578T cell lines, while lycorine was the most active against MCF-7. In alignment with the target prediction outcomes and existing literature, four potential targets were chosen for the molecular docking analysis: CDK8, EGFR, ER-alpha, and dCK. The docking scores revealed two potential targets for the alkaloids with scores similar to co-crystallized inhibitors and substrates: CDK8 and dCK. A visual analysis of the optimal docked configurations indicates that the alkaloids may interact with some key residues in contrast to the other docked compounds. This observation implies their potential to bind effectively to both targets.
CONCLUSIONS: In vitro and in silico results corroborate with data literature suggesting the Amaryllidaceae alkaloids as interesting molecules with antitumoral properties, especially montanine, which showed the best in vitro results against colorectal and breast carcinoma. More studies are necessary to confirm the targets and pharmaceutical potential of montanine against these cancer cell lines.
OBJECTIVE: The objective of this work was to evaluate the potential of three Amaryllidaceae alkaloids against four cancer cell lines.
METHODS: The alkaloids lycorine, 1-O-acetylcaranine, and montanine were evaluated in vitro against colon adenocarcinoma cell line (HCT-116) and breast carcinoma cell lines (MCF-7, MDAMB231, and Hs578T). Computational experiments (target prediction and molecular docking) were conducted to gain a deeper comprehension of possible interactions between these alkaloids and potential targets associated with these tumor cells.
RESULTS: Montanine presented the best results against HCT-116, MDAMB231, and Hs578T cell lines, while lycorine was the most active against MCF-7. In alignment with the target prediction outcomes and existing literature, four potential targets were chosen for the molecular docking analysis: CDK8, EGFR, ER-alpha, and dCK. The docking scores revealed two potential targets for the alkaloids with scores similar to co-crystallized inhibitors and substrates: CDK8 and dCK. A visual analysis of the optimal docked configurations indicates that the alkaloids may interact with some key residues in contrast to the other docked compounds. This observation implies their potential to bind effectively to both targets.
CONCLUSIONS: In vitro and in silico results corroborate with data literature suggesting the Amaryllidaceae alkaloids as interesting molecules with antitumoral properties, especially montanine, which showed the best in vitro results against colorectal and breast carcinoma. More studies are necessary to confirm the targets and pharmaceutical potential of montanine against these cancer cell lines.
摘要：
背景：石豆科植物，如颠茄，几千年来一直被用作草药来解决各种疾病，包括今天可能被确定为癌症的疾病。
目的：这项工作的目的是评估三种石豆科生物碱对四种癌细胞系的潜力。
方法：生物碱lycorine，1-O-乙酰花青素,并在体外对结肠腺癌细胞系（HCT-116）和乳腺癌细胞系（MCF-7，MDAMB231和Hs578T）进行了评估。进行计算实验（靶标预测和分子对接）以更深入地理解这些生物碱与与这些肿瘤细胞相关的潜在靶标之间的可能相互作用。
结果：Montanine对HCT-116，MDAMB231和Hs578T细胞系表现出最好的结果，而石蒜碱对MCF-7最活跃。与目标预测结果和现有文献一致，选择了四个潜在的目标进行分子对接分析：CDK8，EGFR，ER-alpha,还有DCK.对接得分揭示了生物碱的两个潜在靶标，得分与共结晶抑制剂和底物相似：CDK8和dCK。最佳对接构型的视觉分析表明，与其他对接化合物相比，生物碱可能与一些关键残基相互作用。这一观察结果暗示了它们有效结合两个靶标的潜力。
结论：体外和计算机结果证实了数据文献，表明石豆科生物碱是具有抗肿瘤特性的有趣分子，尤其是Montanine,对大肠癌和乳腺癌的体外治疗效果最好。需要更多的研究来确认褐煤碱针对这些癌细胞系的靶标和药物潜力。
目的：这项工作的目的是评估三种石豆科生物碱对四种癌细胞系的潜力。
方法：生物碱lycorine，1-O-乙酰花青素,并在体外对结肠腺癌细胞系（HCT-116）和乳腺癌细胞系（MCF-7，MDAMB231和Hs578T）进行了评估。进行计算实验（靶标预测和分子对接）以更深入地理解这些生物碱与与这些肿瘤细胞相关的潜在靶标之间的可能相互作用。
结果：Montanine对HCT-116，MDAMB231和Hs578T细胞系表现出最好的结果，而石蒜碱对MCF-7最活跃。与目标预测结果和现有文献一致，选择了四个潜在的目标进行分子对接分析：CDK8，EGFR，ER-alpha,还有DCK.对接得分揭示了生物碱的两个潜在靶标，得分与共结晶抑制剂和底物相似：CDK8和dCK。最佳对接构型的视觉分析表明，与其他对接化合物相比，生物碱可能与一些关键残基相互作用。这一观察结果暗示了它们有效结合两个靶标的潜力。
结论：体外和计算机结果证实了数据文献，表明石豆科生物碱是具有抗肿瘤特性的有趣分子，尤其是Montanine,对大肠癌和乳腺癌的体外治疗效果最好。需要更多的研究来确认褐煤碱针对这些癌细胞系的靶标和药物潜力。
