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蕨藻提取物的植物化学分析、抗氧化活性及细胞毒性作用，其可诱导KON口腔癌细胞凋亡及亚G/G0-G1期细胞周期阻滞

Phytochemical analysis, antioxidant activity, and cytotoxic effects of Caulerpa lentillifera extracts inducing cell apoptosis and sub-G/G0-G1 cell cycle arrest in KON oral cancer cells.

作者信息

Manmuan Suwisit, Sirirak Thanchanok, Tubtimsri Sukannika, Petchsomrit Arpa, Chuenbarn Tiraniti

机构信息

Division of Pharmacology and Biopharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi, Thailand.

Division of Pharmacognosy and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi, Thailand.

出版信息

BMC Complement Med Ther. 2025 Mar 11;25(1):101. doi: 10.1186/s12906-025-04835-9.

DOI:10.1186/s12906-025-04835-9
PMID:40069755
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11899751/
Abstract

BACKGROUND

Marine algae have excellent phytoconstituents with notable biological activity and bioactive therapeutic benefits, but the anti-oral cancer activity of Caulerpa lentillifera (C. lentillifera) has not been widely studied. This study aimed to explore the anti-cancer properties of C. lentillifera to gain insights into possible treatment approaches.

METHODS

The three C. lentillifera extracts were prepared using the maceration method with methanol (CLM), ethanol (CLE), and acetone (CLA). The chemical composition of extracts of C. lentillifera was investigated. Its metabolite profiles were selectively further investigated using the LC-QTOF MS/MS technique and their antioxidative activity was evaluated. The cytotoxic effect on KON cells and MRC-5 cells was assessed using the MTT test. Morphological changes and apoptosis were examined through Hoechst 33,258 and AO double staining, while DAPI and FDA double labeling were used to observe the nucleus and cytoplasm. Using a flow cytometer, the percentage of cell cycle arrest was calculated and the fraction of cell death was examined.

RESULTS

The CLA exhibited higher quantities of TPC, TFC, chlorophyll a, and chlorophyll b compared to the CLM and CLE. The LC-QTOF MS/MS analysis revealed ten major phytochemicals in the CLA. The three C. lentillifera extracts exhibited antioxidative activity, with the CLE demonstrating significantly higher antioxidant activity compared to the CLM and CLA. In-vitro, the KON oral cancer cells exhibited sensitivity to CLA, CLE, and CLM in that order. The three extracts induced ROS-mediated cell death as well as disruption of mitochondrial membrane potential, with concentrations at IC, IC, and IC leading to apoptosis within 24 h. Furthermore, the cell cycle of KON cells was blocked in sub-G and G0-G1 by all three extracts. Notably, the extracts significantly impeded colony growth, migration, and invasion. The increase in cellular uptake was measured using the TEER test.

CONCLUSION

The findings showed that C. lentillifera has several functional metabolites, antioxidative activity, and strong anti-tumor properties. According to these results, C. lentillifera extracts may be utilized to treat oral cancer.

摘要

背景

海藻具有优良的植物成分，具有显著的生物活性和生物活性治疗益处，但蕨藻的抗口腔癌活性尚未得到广泛研究。本研究旨在探索蕨藻的抗癌特性，以深入了解可能的治疗方法。

方法

采用浸渍法，分别用甲醇（CLM）、乙醇（CLE）和丙酮（CLA）制备三种蕨藻提取物。对蕨藻提取物的化学成分进行了研究。使用LC-QTOF MS/MS技术对其代谢物谱进行了选择性进一步研究，并评估了它们的抗氧化活性。使用MTT试验评估对KON细胞和MRC-5细胞的细胞毒性作用。通过Hoechst 33,258和AO双重染色检查形态变化和凋亡，而使用DAPI和FDA双重标记观察细胞核和细胞质。使用流式细胞仪计算细胞周期停滞的百分比并检查细胞死亡分数。

结果

与CLM和CLE相比，CLA的总酚含量（TPC）、总黄酮含量（TFC）、叶绿素a和叶绿素b含量更高。LC-QTOF MS/MS分析揭示了CLA中的十种主要植物化学物质。三种蕨藻提取物均表现出抗氧化活性，其中CLE的抗氧化活性明显高于CLM和CLA。在体外，KON口腔癌细胞对CLA、CLE和CLM的敏感性依次降低。三种提取物均诱导活性氧（ROS）介导的细胞死亡以及线粒体膜电位的破坏，IC、IC和IC浓度在24小时内导致细胞凋亡。此外，所有三种提取物均使KON细胞的细胞周期停滞在亚G期和G0-G1期。值得注意的是，提取物显著阻碍了集落生长、迁移和侵袭。使用跨上皮电阻（TEER）试验测量细胞摄取的增加。

结论

研究结果表明，蕨藻具有多种功能性代谢产物、抗氧化活性和强大的抗肿瘤特性。根据这些结果，蕨藻提取物可用于治疗口腔癌。

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