Bufalin Inhibits hTERT Expression and Colorectal Cancer Cell Growth by Targeting CPSF4

Xie, Yuanfang; Tai, Yidi; Gao, Yingying; Guo, Wei; Yu, Wei; Li, Jia; Xu, Feng; Hao, Jie; Gao, Yue; Zhao, Xiaomin; Liao, Yun; Jiang, Wei; Liu, Ge; Deng, Wuguo; Cui, Xiaonan

doi:10.1159/000453206

Cited by 27 publications

(15 citation statements)

References 35 publications

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“…Increasing evidence suggests that only a small subpopulation of cancer cells can regenerate [22]. These cells, termed CSCs, are thought to cause the initiation, therapeutic resistance, metastasis, and recurrence of cancer [2, 34, 35]. Accordingly, it is crucial to identify markers specific to CSCs to facilitate the development of targeted cancer therapies [5, 16].…”

Section: Discussionmentioning

confidence: 99%

Lgr5+CD44+EpCAM+ Strictly Defines Cancer Stem Cells in Human Colorectal Cancer

Leng

Xia

Chen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Although EpCAM+CD44+ cells exhibit more stem-like properties than did EpCAM-CD44- cells, the specificity of EpCAM combined with CD44 in defining CSCs needs further improvement. Lgr5 is used as a biomarker to isolate cancer stem cells (CSCs) in colorectal cancer. However, it remains unclear whether Lgr5, along with EpCAM and CD44, can further identify and define CSCs in colorectal cancer. Methods: Lgr5+CD44+EpCAM+, Lgr5+CD44+EpCAM-, Lgr5+CD44-EpCAM+, Lgr5-CD44+EpCAM+, and Lgr5-CD44-EpCAM-cells were separately isolated using fluorescence-activated cell sorting (FACS). Colony formation, self-renewal, differentiation, and tumorigenic properties of these cells were investigated through in vitro experiments and in vivo tumor xenograft models. The expression of stemness genes and CSC- and epithelial-mesenchymal transition (EMT)-related genes, such as KLF4, Oct4, Sox2, Nanog, CD133, CD44, CD166, ALDH1, Lgr5, E-cadherin, ZO-1, Vimentin, Snail, Slug, and Twist, was examined using real-time PCR. Results: Lgr5-positive subpopulations exhibited higher capacities for colony formation, self-renewal, differentiation, and tumorigenicity as well as higher expression of stemness genes and mesenchymal genes and lower expression of epithelial genes than did Lgr5-negative subpopulations. Conclusion: Our data revealed that tumorigenic cells were highly restricted to Lgr5-positive subpopulations. Most importantly, Lgr5+CD44+EpCAM+ cells exhibited more pronounced CSC-like traits than did any other subpopulation, indicating that Lgr5 combined with CD44 and EpCAM can further improve the stem-like traits of CSCs in colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

Lgr5+CD44+EpCAM+ Strictly Defines Cancer Stem Cells in Human Colorectal Cancer

Leng

Xia

Chen

et al. 2018

Cell Physiol Biochem

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“…While the bacterial species that resulted in pronounced reduction in proliferation were also tested on TIGKs as non-cancer cell control, it should be noted that immortalized cells bypass senescence similar to cancer cells, and most cancer cells also show an increased expression of hTERT proteins (Boehm and Hahn, 2004 ; Zhang et al, 2016 ). Therefore, it may have been more reliable to use primary gingival keratinocytes for assessing differential effects of the bacterial species on cancer vs. non-cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Screening of Health-Associated Oral Bacteria for Anticancer Properties in vitro

Baraniya

Jain

Lucarelli

et al. 2020

Front. Cell. Infect. Microbiol.

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While extensive literature exists about the role of oral bacterial pathogens like Porphyromonas gingivalis and Fusobacterium nucleatum in oral squamous cell carcinoma (OSCC), the role of health-associated species has been largely unexplored. In this study, we assessed the effect of Streptococcus mitis, Rothia mucilaginosa, Neisseria flavescens, Haemophilus parainfluenzae, Lautropia mirabilis , and Veillonella parvula on proliferation and expression of marker genes (IL-6, TNF-α, MMP3, CD36, CCD1, and NANOG) in OSCC cell lines CAL27, SCC25, and SCC4. Porphyromonas gingivalis was included as a pathogenic control. Both bacterial lysates (3 concentrations) and live cells (3 MOIs) were tested. S. mitis, H. parainfluenzae , and N. flavescens resulted in substantial, dose-dependent reduction of proliferation, which was found to be mediated by H 2 O 2 for the former and intracellular infection in the latter two species. However, only H. parainfluenzae showed differential antiproliferative effect against the cancer cell lines vs. the normal control (TIGKs). In the gene expression assays, the health-associated species mostly downregulated CD36, a gene that plays an important role in tumor growth and metastasis, while P. gingivalis upregulated it. IL6 and TNF expression, on the other hand, was upregulated by almost all species, particularly the Gram-negatives including P. gingivalis . The effect on other genes was less evident and varied significantly by cell line. This exploratory study is the first insight into how health-associated bacteria may interact with OSCC. Further studies to explore whether the observed effects may have implications for the prevention or treatment of oral cancer are warranted.

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“…Bufalin is a kind of cardiac glycosides which is derived from the serous fluid secreted by the parotid venom glands and skin of Bufo melanostictus and Bufo bufo gargarizans [20]. Researches have showed that Bufalin has many pharmacological activities, including anti-inflammatory, anti-tumor, antiviral, cardiotonic and narcotic effects [21][22][23][24]. Among these effects, the anti-tumor activity of Bufalin has caught the attention of many researchers.…”

Section: Discussionmentioning

confidence: 99%

Anti-tumor Activity of Bufalin by Inhibiting c-MET Mediated MEK/ERK and PI3K/AKT Signaling Pathways in Gallbladder Cancer

Qian¹,

Su²,

Wang³

et al. 2020

J. Cancer

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Gallbladder cancer is one of the most common malignant tumors in the biliary tract. In recent years, the chemotherapy treatment for gallbladder carcinoma has exhibited obvious characteristics of drug resistance and insensitivity, and one of the main factors is the existence of cancer stem cells. Here in this study, the effect of Bufalin on gallbladder cancer (GBC-SD) cells and the related mechanism were studied. The results indicated that Bufalin could inhibit the growth of gallbladder carcinoma both in vivo and in vitro. According to the biological behavior analysis, Bufalin induced apoptosis, inhibited the propagation, migration and invasion of GBC-SD cells, and blocked cell cycle at the G2/M stage. Besides, Bufalin inhibited the tumor sphere formation capability of gallbladder carcinoma in matrigel, reduced the expression of multiple stemness-associated proteins, including Oct4, Sox2 and the stem cell-surface marker proteins CD133 and CD44. Western blot assay showed that Bufalin inhibited MEK/ERK and PI3-K/AKT signaling pathways by inhibiting the expression of p-c-Met, which in turn affected the expression of apoptosis-related protein Mcl-1, and the invasion-associated proteins E-cadherin, MMP9 and Snail. Bufalin was found to have an inhibitory effect on the GBC-SD cell growth and reduce the self-renewal and characteristic of gallbladder cancer stem cells. It enhanced the chemotherapeutic sensitivity and reduced the metastasis of gallbladder carcinoma. In conclusion, Bufalin can be used as a new promising anticancer drug for gallbladder cancer patients who are resistant to traditional chemotherapy.

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Bufalin Inhibits hTERT Expression and Colorectal Cancer Cell Growth by Targeting CPSF4

Cited by 27 publications

References 35 publications

Lgr5+CD44+EpCAM+ Strictly Defines Cancer Stem Cells in Human Colorectal Cancer

Lgr5+CD44+EpCAM+ Strictly Defines Cancer Stem Cells in Human Colorectal Cancer

Screening of Health-Associated Oral Bacteria for Anticancer Properties in vitro

Anti-tumor Activity of Bufalin by Inhibiting c-MET Mediated MEK/ERK and PI3K/AKT Signaling Pathways in Gallbladder Cancer

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