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Thymol Isolated from Thymus vulgaris L. Inhibits Colorectal Cancer Cell Growth and Metastasis by Suppressing the Wnt/β-Catenin Pathway.
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2020-07-01 , DOI: 10.2147/dddt.s254218 Qiongyao Zeng 1, 2 , Yuncheng Che 2 , Yu Zhang 3 , Mei Chen 2 , Qiang Guo 1, 2, 3 , Wenjing Zhang 2, 4
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2020-07-01 , DOI: 10.2147/dddt.s254218 Qiongyao Zeng 1, 2 , Yuncheng Che 2 , Yu Zhang 3 , Mei Chen 2 , Qiang Guo 1, 2, 3 , Wenjing Zhang 2, 4
Affiliation
Purpose: Colorectal cancer (CRC) is one of the most commonly occurring cancers and is associated with high morbidity and mortality. Nevertheless, there is currently no safe and effective treatment for this condition. Thymol is a phenolic compound that is recognized as safe for use in food as well as medical and cosmetic fields. Increasing evidence has indicated that thymol exerts prominent antitumor effects in a variety of cancers, including CRC. However, how thymol elicits these effects on CRC and the associated underlying mechanisms remains unclear.
Methods: HCT116 and Lovo cells were treated with different concentrations of thymol. Cell Counting Kit-8 (CCK-8) and transwell migration and invasion assays were used to evaluate cell proliferation, migration, and invasion, respectively. Cell apoptosis and cell cycle distribution were measured by flow cytometry. RT-qPCR, Western blot, and immunohistochemistry were used to detect the expression of related genes and their protein products.
Results: In this study, we tested the antitumor activity of thymol extracted from a Chinese medicinal herb, Thymus vulgaris L. We show that thymol treatment in vitro inhibited cell proliferation and induced apoptosis and cell cycle arrest in CRC. Furthermore, in vivo treatment with 75 and 150 mg/kg thymol led to a significant decrease in tumor volume. Thymol administration induced CRC cell apoptosis through activation of the BAX/Bcl-2 signaling pathway. In addition, thymol suppressed CRC cell epithelial–mesenchymal transition (EMT), invasion, and metastasis via inhibiting the activation of the Wnt/β-catenin pathway, both in vitro and in vivo.
Conclusion: Thymol may prevent CRC progression through inhibition of the Wnt/β-catenin signaling pathway, highlighting its potential as a novel therapeutic option for the treatment of CRC.
Keywords: Wnt/β-catenin, colorectal cancer, thymol, tumor growth and metastasis
中文翻译：
从 Thymus vulgaris L. 中分离出的百里酚通过抑制 Wnt/β-Catenin 通路抑制结肠直肠癌细胞的生长和转移。
目的：结直肠癌（CRC）是最常见的癌症之一，与高发病率和死亡率相关。然而，目前还没有针对这种情况的安全有效的治疗方法。百里酚是一种酚类化合物，被认为可安全用于食品以及医疗和化妆品领域。越来越多的证据表明，百里酚在包括 CRC 在内的多种癌症中发挥显着的抗肿瘤作用。然而，百里酚如何引起这些对 CRC 的影响以及相关的潜在机制仍不清楚。
方法：用不同浓度的百里酚处理 HCT116 和 Lovo 细胞。Cell Counting Kit-8 (CCK-8) 和 transwell 迁移和侵袭测定分别用于评估细胞增殖、迁移和侵袭。通过流式细胞术测量细胞凋亡和细胞周期分布。采用RT-qPCR、Western blot和免疫组化检测相关基因及其蛋白产物的表达。
结果：在这项研究中，我们测试了从中药百里香中提取的百里香酚的抗肿瘤活性。L. 我们表明，体外百里酚处理可抑制 CRC 中的细胞增殖并诱导细胞凋亡和细胞周期停滞。此外，用 75 和 150 mg/kg 麝香草酚进行体内治疗导致肿瘤体积显着减少。百里酚通过激活 BAX/Bcl-2 信号通路诱导 CRC 细胞凋亡。此外，百里酚在体外和体内均通过抑制 Wnt/β-catenin 通路的激活来抑制 CRC 细胞上皮间质转化 (EMT)、侵袭和转移。
结论：百里酚可通过抑制 Wnt/β-catenin 信号通路来预防 CRC 进展，突出其作为治疗 CRC 的新治疗选择的潜力。
关键词： Wnt/β-catenin，结直肠癌，百里酚，肿瘤生长和转移
更新日期：2020-06-30
Methods: HCT116 and Lovo cells were treated with different concentrations of thymol. Cell Counting Kit-8 (CCK-8) and transwell migration and invasion assays were used to evaluate cell proliferation, migration, and invasion, respectively. Cell apoptosis and cell cycle distribution were measured by flow cytometry. RT-qPCR, Western blot, and immunohistochemistry were used to detect the expression of related genes and their protein products.
Results: In this study, we tested the antitumor activity of thymol extracted from a Chinese medicinal herb, Thymus vulgaris L. We show that thymol treatment in vitro inhibited cell proliferation and induced apoptosis and cell cycle arrest in CRC. Furthermore, in vivo treatment with 75 and 150 mg/kg thymol led to a significant decrease in tumor volume. Thymol administration induced CRC cell apoptosis through activation of the BAX/Bcl-2 signaling pathway. In addition, thymol suppressed CRC cell epithelial–mesenchymal transition (EMT), invasion, and metastasis via inhibiting the activation of the Wnt/β-catenin pathway, both in vitro and in vivo.
Conclusion: Thymol may prevent CRC progression through inhibition of the Wnt/β-catenin signaling pathway, highlighting its potential as a novel therapeutic option for the treatment of CRC.
Keywords: Wnt/β-catenin, colorectal cancer, thymol, tumor growth and metastasis
中文翻译：
从 Thymus vulgaris L. 中分离出的百里酚通过抑制 Wnt/β-Catenin 通路抑制结肠直肠癌细胞的生长和转移。
目的：结直肠癌（CRC）是最常见的癌症之一，与高发病率和死亡率相关。然而，目前还没有针对这种情况的安全有效的治疗方法。百里酚是一种酚类化合物，被认为可安全用于食品以及医疗和化妆品领域。越来越多的证据表明，百里酚在包括 CRC 在内的多种癌症中发挥显着的抗肿瘤作用。然而，百里酚如何引起这些对 CRC 的影响以及相关的潜在机制仍不清楚。
方法：用不同浓度的百里酚处理 HCT116 和 Lovo 细胞。Cell Counting Kit-8 (CCK-8) 和 transwell 迁移和侵袭测定分别用于评估细胞增殖、迁移和侵袭。通过流式细胞术测量细胞凋亡和细胞周期分布。采用RT-qPCR、Western blot和免疫组化检测相关基因及其蛋白产物的表达。
结果：在这项研究中，我们测试了从中药百里香中提取的百里香酚的抗肿瘤活性。L. 我们表明，体外百里酚处理可抑制 CRC 中的细胞增殖并诱导细胞凋亡和细胞周期停滞。此外，用 75 和 150 mg/kg 麝香草酚进行体内治疗导致肿瘤体积显着减少。百里酚通过激活 BAX/Bcl-2 信号通路诱导 CRC 细胞凋亡。此外，百里酚在体外和体内均通过抑制 Wnt/β-catenin 通路的激活来抑制 CRC 细胞上皮间质转化 (EMT)、侵袭和转移。
结论：百里酚可通过抑制 Wnt/β-catenin 信号通路来预防 CRC 进展，突出其作为治疗 CRC 的新治疗选择的潜力。
关键词： Wnt/β-catenin，结直肠癌，百里酚，肿瘤生长和转移
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