Babao Dan is a robust anti-tumor agent via inhibiting wnt/β-catenin activation and cancer cell stemness

被引:10
|
作者
Xie, Xinxin [1 ]
Chen, Jinxiao [1 ]
Wo, Da [1 ]
Ma, En [2 ]
Ning, Yongling [1 ]
Peng, Jun [1 ]
Zhu, Weidong [1 ]
Ren, Dan-ni [1 ]
机构
[1] Fujian Univ Tradit Chinese Med, Acad Integrat Med, Fujian Key Lab Integrat Med Geriatr, 1 Qiuyang Rd, Fuzhou 350122, Fujian, Peoples R China
[2] Tongji Univ, Sch Med, Minist Educ, Key Lab Arrhythmias,Clin & Translat Res Ctr,Res I, Shanghai, Peoples R China
关键词
Hepatoblastoma; Babao dan; Wnt/beta-catenin signaling; Cancer stem cell; EpCAM; Anti-Tumor; BETA-CATENIN; HEPATOBLASTOMA; EPCAM; HOMEOSTASIS; TRITERPENE; PATHWAY; MARKER;
D O I
10.1016/j.jep.2021.114449
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
Ethnopharmacological relevance: Traditional Chinese Medicine (TCM) is being increasingly used worldwide due to its diverse efficacy and relatively low side effects. Babao Dan (BBD) is a well-known TCM formula that is currently used for the effective treatment of various cancers, however its underlying molecular mechanism remains unknown. Aim of the study: Tumor growth and tumor recurrence are characterized by two distinct populations of cells, namely the well-differentiated cancer cells composing the majority of tumor bulk, and cancer stem cells (CSCs) involved in tumor relapse, which are both strongly associated with excessive activation of Wnt/beta-catenin signaling. Our study aims to elucidate the underlying molecular mechanisms associated with the anti-tumor proliferative effects of Babao Dan (BBD). Materials and methods: We used a hepatoblastoma cell line HepG2 with stem cell-like traits that harbors a constitutively active mutant of beta-catenin in order to study the anti-tumor ability of BBD via targeting Wnt/beta-catenin signaling. Results: BBD robustly attenuated both the intrinsic and extrinsic activation of Wnt/beta-catenin pathway in HepG2 hepatoblastoma cells, as well as Wnt target genes. Moreover, BBD significantly inhibited both the proliferation of well-differentiated cancer cells, as well as the stem-like property of CSCs as evidenced by EpCAM, a Wnt target gene and a novel marker of cancer cell stemness. In addition, mice administered with BBD using HepG2 cell line derived xenograft model had marked reductions in tumor size and weight, as well as significantly decreased expressions of Wnt target genes and cancer cell stemness. Conclusion: Our findings elucidated the underlying molecular mechanisms associated with the robust anti-tumor effects of BBD via potent inhibition of Wnt/beta-catenin signaling, and implicate its use in the clinical treatment of cancers.
引用
收藏
页数:12
相关论文
共 50 条
  • [21] 5-FU promotes stemness of colorectal cancer via p53-mediated WNT/β-catenin pathway activation
    Cho, Yong-Hee
    Ro, Eun Ji
    Yoon, Jeong-Su
    Mizutani, Tomohiro
    Kang, Dong-Woo
    Park, Jong-Chan
    Kim, Tae Il
    Clevers, Hans
    Choi, Kang-Yell
    NATURE COMMUNICATIONS, 2020, 11 (01)
  • [22] FUBP1 promotes colorectal cancer stemness and metastasis via DVL1-mediated activation of Wnt/β-catenin signaling
    Yin, Haofan
    Gao, Tianxiao
    Xie, Jinye
    Huang, Zhijian
    Zhang, Xiaoyan
    Yang, Fengyu
    Qi, Weiwei
    Yang, Zhonghan
    Zhou, Ti
    Gao, Guoquan
    Yang, Xia
    MOLECULAR ONCOLOGY, 2021, 15 (12) : 3490 - 3512
  • [23] PNO1 enhances ovarian cancer cell growth, invasion, and stemness via activating the AKT/Wnt/β-catenin pathway
    Qin, Lu
    Lu, Jiao
    Qian, Qiaohong
    Tang, Minjie
    Liu, Min
    SCIENTIFIC REPORTS, 2025, 15 (01):
  • [24] HBO1 promotes cell proliferation in bladder cancer via activation of Wnt/-catenin signaling
    Chen, Zhaohui
    Zhou, Lijie
    Wang, Longwang
    Kazobinka, Gallina
    Zhang, Xiaoping
    Han, Xiaomin
    Li, Bin
    Hou, Teng
    MOLECULAR CARCINOGENESIS, 2018, 57 (01) : 12 - 21
  • [25] Manipulating the Wnt/β-catenin signaling pathway to promote anti-tumor immune infiltration into the TME to sensitize ovarian cancer to ICB therapy
    Wall, J. A.
    Meza-Perez, S.
    Scalise, C. B.
    Katre, A.
    Londono, A., I
    Turbitt, W. J.
    Randall, T.
    Norian, L. A.
    Arend, R. C.
    GYNECOLOGIC ONCOLOGY, 2021, 160 (01) : 285 - 294
  • [26] Clinical Significance of Acyl-CoA Dehydrogenase Short Chain and Its Anti-tumor Role in Hepatocellular Carcinoma by Inhibiting Canonical Wnt/β-Catenin Pathway
    Gu, Jiawei
    Cao, Zhipeng
    Niu, Gengming
    Ying, Jianghui
    Wang, Hui
    Jiang, Hua
    Ke, Chongwei
    DIGESTIVE DISEASES AND SCIENCES, 2025, 70 (02) : 622 - 637
  • [27] Triptolide exhibits dual anti-tumor effects through inhibiting autophagy and extracellular matrix activation in pancreatic cancer
    Gu, Jianxiang
    Shi, Zhao
    Zhou, Siqi
    Zhou, Quan
    Nie, Shuang
    Li, Hongzhen
    Shen, Shanshan
    Zou, Xiaoping
    JOURNAL OF CANCER RESEARCH AND THERAPEUTICS, 2024, 20 (07)
  • [28] Robust Anti-Tumor T Cell Response with Efficient Intratumoral Infiltration by Nanodisc Cancer Immunotherapy
    Kuai, Rui
    Singh, Priti B.
    Sun, Xiaoqi
    Xu, Cheng
    Najafabadi, Alireza Hassani
    Scheetz, Lindsay
    Yuan, Wenmin
    Xu, Yao
    Hong, Hao
    Keskin, Derin B.
    Wu, Catherine J.
    Jain, Renu
    Schwendeman, Anna
    Moon, James J.
    ADVANCED THERAPEUTICS, 2020, 3 (09)
  • [29] A novel recombinant human Frizzled-7 protein exhibits anti-tumor activity against triple negative breast cancer via abating Wnt/β-catenin pathway
    Xie, Wei
    Zhang, Yan
    He, Yuan
    Zhang, Kunchi
    Wan, Guoqing
    Huang, Yanjuan
    Zhou, Zhaoli
    Huang, Gang
    Wang, Jin
    INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2018, 103 : 45 - 55
  • [30] Hyper-activation of WNT/β-catenin signaling pathway mediates anti-tumor effects of histone deacetylase inhibitors in acute T lymphoblastic leukemia
    Shao, Na
    Zou, Jie
    Li, Jie
    Chen, Feng
    Dai, Jianjian
    Qu, Xun
    Sun, Xiulian
    Ma, Daoxin
    Ji, Chunyan
    LEUKEMIA & LYMPHOMA, 2012, 53 (09) : 1769 - 1778