scholarly journals Berberine inhibits the proliferation of pancreatic cancer targeting pancreatic cancer stem cells

Author(s):  
Mengmeng Liu ◽  
Yue Pan ◽  
Xufeng Tao ◽  
Ning Li ◽  
Kun Li ◽  
...  

Abstract BackgroundPDAC is universally acknowledged to be one of the highest mortality rate of cancer-related deaths. PCSCs, regulated by EMT, could promote the proliferation of PDAC. Berberine with high medicinal value has usually been used as an anti-cancer agent. Hence the purpose of this study is to investigate the anti-cancer effect of berberine in PDAC. MethodsMTT assay was used to verify berberine inhibiting the proliferation of PDAC. Immunofluorescence staining, stem cell sphere, wound healing and transwell migration assay were demonstrated the anti-proliferation and anti-stemness of PCSCs in vitro . PANC-02 cells were injected in C57BL/6 mice to establish the orthotopic pancreatic-cancer model in vivo . H&E and Ki67 immunohistogical staining assay were used to evaluated the effect of berberine in PDAC in vivo. q-PCR and Western blot methods were applied to detect the expression of EMT procedure.ResultsIn this study, berberine has selective anti-cancer effect in PDAC in vitro . Moreover, berberine suppressed the proliferation and stemness of PCSCs in PDAC. In vivo , berberine reduced the tumor size and decreased the expression of Ki67 in orthotopic pancreatic-cancer pancreases. In addition, berberine inhibit the EMT signaling pathway both in vitro and in vivo . ConclusionsOur study indicates that berberine inhibit the proliferation of PDAC in vivo and vitro . The mechanism of anti-cancer effect on berberine may suppress the PCSCs through inhibiting EMT procedure. Therefore, berberine may be the novel antineoplastic drug with clinical effectiveness in PDAC. Keywords: Berberine, PDAC, PCSCs, EMT, berberine

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 930
Author(s):  
Donatella Delle Cave ◽  
Riccardo Rizzo ◽  
Bruno Sainz ◽  
Giuseppe Gigli ◽  
Loretta L. del Mercato ◽  
...  

Pancreatic cancer, the fourth most common cancer worldwide, shows a highly unsuccessful therapeutic response. In the last 10 years, neither important advancements nor new therapeutic strategies have significantly impacted patient survival, highlighting the need to pursue new avenues for drug development discovery and design. Advanced cellular models, resembling as much as possible the original in vivo tumor environment, may be more successful in predicting the efficacy of future anti-cancer candidates in clinical trials. In this review, we discuss novel bioengineered platforms for anticancer drug discovery in pancreatic cancer, from traditional two-dimensional models to innovative three-dimensional ones.


Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 33
Author(s):  
Hee Ra Jung ◽  
Seongman Jo ◽  
Min Jae Jeon ◽  
Hyelim Lee ◽  
Yeonjeong Chu ◽  
...  

In cancer immunotherapy, the cyclic GMP–AMP synthase–stimulator of interferon genes (STING) pathway is an attractive target for switching the tumor immunophenotype from ‘cold’ to ‘hot’ through the activation of the type I interferon response. To develop a new chemical entity for STING activator to improve cyclic GMP-AMP (cGAMP)-induced innate immune response, we identified KAS-08 via the structural modification of DW2282, which was previously reported as an anti-cancer agent with an unknown mechanism. Further investigation revealed that direct STING binding or the enhanced phosphorylation of STING and downstream effectors were responsible for DW2282-or KAS-08-mediated STING activity. Furthermore, KAS-08 was validated as an effective STING pathway activator in vitro and in vivo. The synergistic effect of cGAMP-mediated immunity and efficient anti-cancer effects successfully demonstrated the therapeutic potential of KAS-08 for combination therapy in cancer treatment.


2018 ◽  
Vol 47 (5) ◽  
pp. 2109-2125 ◽  
Author(s):  
Zhaocong Yang ◽  
Yanfeng Zhang ◽  
Tingting Tang ◽  
Qinhua Zhu ◽  
Wanyue Shi ◽  
...  

Background/Aims: Pancreatic cancer remains one of the deadliest human malignancies, the lethality of which may be attributed to the presence of pancreatic cancer stem cells (PCSCs), a small subpopulation of cells existing within pancreatic tumor with high carcinogenesis. Therefore, it is crucial to establish an efficient enrichment and culture system of PCSCs and identify the key genes involved in the regulation of PCSCs. The three-dimensional (3D) liquid suspension mammosphere culture system has been established for enrichment and culture of PCSCs in vitro as the cell spheres are likely to originate from individual cell clone, but it has been challenged because the cell spheroids could be a result of cell aggregation. Methods: We optimized the existing culture system by adding methylcellulose to create a 3D semi-solid system which prevented the non-specific aggregation. Then we identified the CSC properties of Panc-1 spheroid cells cultured by this system by detecting the genes associated with stemness and by evaluation of the tumorigenicity in vitro and in vivo through invasion, migration and xenograft experiments methods. Subsequently, we performed high-throughput sequencing (HTS) of the Panc-1 spheroid cells. Results: We confirmed the PCSCs properties and high malignancy of the Panc-1 spheroid cells enriched by our novel 3D semi-solid system both in vitro and in vivo. Hundreds of mRNA, microRNA (miRNA) and dozens of long non-coding RNA (LncRNA) were identified to be differentially regulated in PCSCs-like Panc-1 spheroid cells compared with their parental cells by HTS. Conclusions: Our results demonstrate an efficient enrichment and culture system for Panc-1 spheroid cells with the PCSCs properties. The differentially expressed genes and their targets identified by the HTS of the Panc-1 spheroid cells can serve as new potential biomarkers for pancreatic cancer diagnosis and targeted therapy.


2020 ◽  
Vol 21 (1) ◽  
pp. 11-24
Author(s):  
Chandrasai Potla Durthi ◽  
Madhuri Pola ◽  
Satish Babu Rajulapati ◽  
Anand Kishore Kola ◽  
Mohammad Amjad Kamal

L-glutaminase has versatile applications in pharma and food industries. In pharmaceutical industry, L-glutaminase can be used as anti-oxidant and anti-cancer agent to treat Acute Lymphocytic Leukaemia (ALL). Whereas, in the food industry, L-glutaminase is used for acrylamide degradation, theanine production, flavour enhancer, soy sauce and many. The other applications include nitrogen metabolism and its use as biosensor in hybridoma technology. Both intra-cellular and extra-cellular L-glutaminases from wide range of sources were identified. Because of its diverse applications, there is a need to improve the production of L-glutaminase by enzyme engineering technology. Effect of recombination on L-glutaminase production was also reported. Researchers also confirmed the antitumor properties of L-glutaminase by conducting in vitro, in vivo and in silico studies. Bacillus sps. and Aspergillus sps. are the commercial producers of L-glutaminase. In this review, the applications, different sources of Lglutaminase, anti-cancer properties were discussed.


2017 ◽  
Vol 126 ◽  
pp. 12-24 ◽  
Author(s):  
Baojian Guo ◽  
Shengquan Hu ◽  
Chengyou Zheng ◽  
Hongyu Wang ◽  
Fangcheng Luo ◽  
...  
Keyword(s):  
Mao B ◽  

2012 ◽  
Vol 47 ◽  
pp. 432-444 ◽  
Author(s):  
Bo Zhong ◽  
Xiaohan Cai ◽  
Snigdha Chennamaneni ◽  
Xin Yi ◽  
Lili Liu ◽  
...  

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