Zhao Yuhang, Wang Min, Tsering Jokyab, Li Hanluo, Li Simin, Li Yuepeng, Liu Yinghua, Hu Xianda
1 Daqing Oilfield General Hospital, Daqing, China.
2 Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Integr Cancer Ther. 2018 Sep;17(3):894-901. doi: 10.1177/1534735418774410. Epub 2018 May 10.
Triphala is a herbal medicine that has been widely used for treating a variety of ailments. This study aims to systematically analyze the antitumor effects of Triphala on gynecological cancers.
The antineoplastic activities of Triphala on gynecological cancers were analyzed using network pharmacology-based strategies. Afterward, the human ovarian cancer cell line SK-OV-3, cervical cancer cell line HeLa, and endometrial cancer cell line HEC-1-B were selected for experimetal valification.
Network pharmacology analysis suggested that Triphala could comprehensively intervene in proliferation and apoptosis through diverse signaling pathways, mainly including MAPK/ERK, PI3K/Akt/mTOR, and NF-κB/p53. The Cell Counting Kit 8 (CCK-8) assay illustrated that Triphala was able to inhibit cell proliferation with half inhibition concentration (IC) values of 98.28 ± 13.71, 95.56 ± 8.94, and 101.23 ± 7.76 µg/mL against SK-OV-3, HeLa, and HEC-1-B cells, respectively. The ELISA experiment demonstrated that Triphala was capable of promoting programmed cell death, with dosage correlations. The antiproliferative and proapoptotic activities were confirmed by flow cytometric analysis using Ki67 antibody and Annexin V/propidium iodide (PI) dual staining. Western blotting revealed a decrease in expression levels of phospho-Akt, phospho-p44/42, and phospho-NF-κB p56 in cells administered Triphala, which indicated that the possible mechanism could involve downregulation of MAPK/ERK, PI3K/Akt/mTOR, and NF-κB/p53 signaling pathways, as was predicted.
Triphala holds great promise for treating gynecological cancers. Although the favorable pharmacological properties have been preliminarily investigated in this study, further studies are still needed to uncover the sophisticated mechanism of Triphala in cancer therapy.
三果木是一种已被广泛用于治疗多种疾病的草药。本研究旨在系统分析三果木对妇科癌症的抗肿瘤作用。
采用基于网络药理学的策略分析三果木对妇科癌症的抗肿瘤活性。随后，选择人卵巢癌细胞系SK-OV-3、宫颈癌细胞系HeLa和子宫内膜癌细胞系HEC-1-B进行实验验证。
网络药理学分析表明，三果木可通过多种信号通路全面干预增殖和凋亡，主要包括MAPK/ERK、PI3K/Akt/mTOR和NF-κB/p53。细胞计数试剂盒8（CCK-8）检测表明，三果木能够抑制细胞增殖，对SK-OV-3、HeLa和HEC-1-B细胞的半数抑制浓度（IC）值分别为98.28±13.71、95.56±8.94和101.23±7.76μg/mL。ELISA实验表明，三果木能够促进程序性细胞死亡，具有剂量相关性。使用Ki67抗体和膜联蛋白V/碘化丙啶（PI）双重染色的流式细胞术分析证实了其抗增殖和促凋亡活性。蛋白质免疫印迹法显示，给予三果木的细胞中磷酸化Akt、磷酸化p44/42和磷酸化NF-κB p56的表达水平降低，这表明可能的机制可能涉及如预测的MAPK/ERK、PI3K/Akt/mTOR和NF-κB/p53信号通路的下调。
三果木在治疗妇科癌症方面具有很大的潜力。尽管本研究已初步研究了其良好的药理特性，但仍需要进一步研究以揭示三果木在癌症治疗中的复杂机制。
