A novel Rhein derivative: Activation of Rac1/NADPH pathway enhances sensitivity of nasopharyngeal carcinoma cells to radiotherapy

Su, Zhengying; Li, Zhaoquan; Wang, Chunmiao; Tian, Wei; Fu, Lan; Liang, Dandan; Li, Junying; Li, Danrong; Hou, Huaxin

doi:10.1016/j.cellsig.2018.11.015

Cited by 21 publications

(11 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The CNE1 and CNE2 were the first and second strains established by the Chinese Academy of Preventive Medicine and have been widely used in various researches. The differentiation characteristics have also been confirmed by other report [19]. In this study, these cell lines were commercially purchased from the company (Taisheng Biotech., Guangzhou, China) and cultured in RPMI-1640 medium supplemented with 100 U/mL streptomycin, 100 U/mL penicillin, and 10% Newborn Calf Serum (Invitrogen Corporation, USA).…”

Section: Methodssupporting

confidence: 78%

Metabolic characteristics revealing cell differentiation of nasopharyngeal carcinoma by combining NMR spectroscopy with Raman spectroscopy

Chen

et al. 2019

Cancer Cell Int

View full text Add to dashboard Cite

Background The staging system of nasopharyngeal carcinoma (NPC) has close relationship with the degree of cell differentiation, but most NPC patients remain undiagnosed until advanced phases. Novel metabolic markers need to be characterized to support diagnose at an early stage. Methods Metabolic characteristics of nasopharyngeal normal cell NP69 and two types of NPC cells, including CNE1 and CNE2 associated with high and low differentiation degrees were studied by combining 1 H NMR spectroscopy with Raman spectroscopy. Statistical methods were also utilized to determine potential characteristic metabolites for monitoring differentiation progression. Results Metabolic profiles of NPC cells were significantly different according to differentiation degrees. Various characteristic metabolites responsible for different differentiated NPC cells were identified, and then disordered metabolic pathways were combed according to these metabolites. We found disordered pathways mainly included amino acids metabolisms like essential amino acids metabolisms, as well as altered lipid metabolism and TCA cycle, and abnormal energy metabolism. Thus our results provide evidence about close relationship between differentiation degrees of NPC cells and the levels of intracellular metabolites. Moreover, Raman spectrum analysis also provided complementary and confirmatory information about intracellular components in single living cells. Eight pathways were verified to that in NMR analysis, including amino acids metabolisms, inositol phosphate metabolism, and purine metabolism. Conclusions Methodology of NMR-based metabolomics combining with Raman spectroscopy could be powerful and straightforward to reveal cell differentiation development and meanwhile lay the basis for experimental and clinical practice to monitor disease progression and therapeutic evaluation. Electronic supplementary material The online version of this article (10.1186/s12935-019-0759-4) contains supplementary material, which is available to authorized users.

show abstract

Section: Methodssupporting

confidence: 78%

Metabolic characteristics revealing cell differentiation of nasopharyngeal carcinoma by combining NMR spectroscopy with Raman spectroscopy

Chen

et al. 2019

Cancer Cell Int

View full text Add to dashboard Cite

show abstract

“…Similarly, Rac1 also affects the sensitivity of cancer to radiotherapy. RP-4, a new type of radiosensitizer derived from rhein, activates the sensitivity of nasopharyngeal carcinoma (NPC) cells to radiotherapy by targeting the Rac1-NADPH pathway (149). Our research team has confirmed that Rac1 can target the PAK1-LIMK1-Cofilins signaling pathway to cause radiotherapy resistance in lung cancer (150).…”

Section: Rac1 Is Involved In the Regulation Of Resistance To Tumor Therapymentioning

confidence: 74%

Rac1, A Potential Target for Tumor Therapy

et al. 2021

View full text Add to dashboard Cite

RAS-related C3 botulinum toxin substrate 1 (Rac.1) is one of the important members of Rho GTPases. It is well known that Rac1 is a cytoskeleton regulation protein that regulates cell adhesion, morphology, and movement. Rac1 is highly expressed in different types of tumors, which is related to poor prognosis. Studies have shown that Rac1 not only participates in the tumor cell cycle, apoptosis, proliferation, invasion, migration and angiogenesis, but also participates in the regulation of tumor stem cell, thus promoting the occurrence of tumors. Rac1 also plays a key role in anti-tumor therapy and participates in immune escape mediated by the tumor microenvironment. In addition, the good prospects of Rac1 inhibitors in cancer prevention and treatment are exciting. Therefore, Rac1 is considered as a potential target for the prevention and treatment of cancer. The necessity and importance of Rac1 are obvious, but it still needs further study.

show abstract

“…One target of Rac1 during DNA-damage and induction of apoptosis is JNK 14–18 . The Rac1/JNK pathway has been involved in doxorubicin-induced apoptosis of cardiomyocytes and human cancer cells 18,32,33 . Previously, we found in T-ALL cells that doxorubicin-induced JNK activity promoted apoptosis by downregulating the levels of anti-apoptotic protein Mcl-1, and collagen inhibited JNK activation and restored Mcl-1 levels 6 .…”

Section: Resultsmentioning

confidence: 99%

Cell adhesion to collagen promotes leukemia resistance to doxorubicin by reducing DNA damage through the inhibition of Rac1 activation

Naci

Berrazouane

Barabé

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Chemoresistance is a major hurdle in anti-cancer therapy. Growing evidence indicates that integrin-mediated cell adhesion to extracellular matrix plays a major role in chemoresistance. However, the underlying mechanisms are not fully understood. We have previously shown that the collagen-binding integrin α2β1 promoted doxorubicin resistance in acute T cell lymphoblastic leukemia (T-ALL). In this study, we found that acute myeloid leukemia (AML) cell lines also express α2β1 integrin and collagen promoted their chemoresistance as well. Furthermore, we found that high levels of α2 integrin correlate with worse overall survival in AML. Our results showed that doxorubicin-induced apoptosis in leukemic cells is associated with activation of Ras-related C3 botulinum toxin substrate 1 (Rac1) and that collagen inhibited this pathway. The protective effect of collagen is associated with the inhibition of Rac1-induced DNA damage as evaluated by the comet assay and the phosphorylated levels of histone H2AX (γ-H2AX). Together these results show that by inhibiting pro-apoptotic Rac1, α2β1 integrin can be a major pathway protecting leukemic cells from genotoxic agents and may thus represent an important therapeutic target in anti-cancer treatment.

show abstract

A novel Rhein derivative: Activation of Rac1/NADPH pathway enhances sensitivity of nasopharyngeal carcinoma cells to radiotherapy

Cited by 21 publications

References 31 publications

Metabolic characteristics revealing cell differentiation of nasopharyngeal carcinoma by combining NMR spectroscopy with Raman spectroscopy

Metabolic characteristics revealing cell differentiation of nasopharyngeal carcinoma by combining NMR spectroscopy with Raman spectroscopy

Rac1, A Potential Target for Tumor Therapy

Cell adhesion to collagen promotes leukemia resistance to doxorubicin by reducing DNA damage through the inhibition of Rac1 activation

Contact Info

Product

Resources

About