Targeting autophagy in cancer stem cells as an anticancer therapy

Lei, Yuanyuan; Zhang, Dan; Yu, Jin; Dong, Hui; Zhang, Jianwei; Yang, Shiming

doi:10.1016/j.canlet.2017.02.012

Cited by 95 publications

(69 citation statements)

References 73 publications

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“…This suggests a central role of the quinoline fragment of 4 and 5 in promoting cell survival. That a treatment targeting autophagy shows selectivity toward tumor cells rather than healthy cells, is highly desirable, since questions have been raised on the possible side effects of such a therapeutic treatment, because autophagy is a physiological process, which is found in many different (healthy) tissues of the body . Further studies in vivo will be necessary to assess the selectivity of the ruthenacarborane complexes, against a broader panel of healthy cells and tissues.…”

Section: Resultsmentioning

confidence: 99%

Quinoline‐Conjugated Ruthenacarboranes: Toward Hybrid Drugs with a Dual Mode of Action

et al. 2019

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The role of autophagy in cancer is often complex, ranging from tumor-promoting to -suppressing effects. In this study, two novel hybrid molecules were designed, containing a ruthenacarborane fragment conjugated with a known modulator of autophagy, namely a quinoline derivative. The complex closo-[3-(η 6 -p-cymene)-1-(quinolin-8-yl-acetate)-3,1,2-RuC 2 B 9 H 10 ](4) showed a dual mode of action against the LN229 (human glioblastoma) cell line, where it inhibited tumor-promoting autophagy, and strongly inhibited cell proliferation, de facto blocking cellular division. These results, together with the tendency to spontaneously form nanoparticles in aqueous solution, make complex 4 a very promising drug candidate for further studies in vivo, for the treatment of autophagy-prone glioblastomas. [a] Dr. . Results from flow cytometric and fluorescence microscopy analysis, and wound healing assay of MCF-7 cells incubated (72 h) with 3 and 4 at 20 μM. (A) CFSE staining (left panel) and wound healing assay (right panel); (B) AnnV/PI double staining; (C) DAPI-stained cells observed under fluorescence microscope (magnification X200). Arrows indicate apoptotic cells; (D) ApoStat staining; (E) AO staining. Experiments were run in triplicate. One representative example per each experiment is shown. For each staining protocol, the respective control (untreated cells) is also shown. (FL1, green channel; FL2, orange channel; FL3, dark red channel).

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Section: Resultsmentioning

confidence: 99%

Quinoline‐Conjugated Ruthenacarboranes: Toward Hybrid Drugs with a Dual Mode of Action

et al. 2019

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“…Autophagy inhibition decreases the properties of CSCs in JEC spheres. It has been reported that autophagy plays an important role in CSC maintenance, plasticity and survival (17)(18)(19) and takes part in the dynamic transformation between normal cancer cells and CSC in pancreatic cancer (27,28). In order to clarify if autophagy inhibition could influence the dynamic transformation of ECSCs, conventional autophagy inhibitors 3-MA and Cq were added during the successive spheroid culture, respectivly, then the relative expression of CSC markers was detected by qPCR and western blotting.…”

Section: Cd133mentioning

confidence: 99%

“…It is proposed that there is a close relationship between cancer stem cells and autophagy. Accumulating evidence provides insight into the function of autophagy in maintenance, plasticity and survival (17)(18)(19). CSCs have higher autophagy than normal cancer cells and are more sensitive to autophagy inhibition compared to cells not expressing CSC markers (20).…”

Section: Introductionmentioning

confidence: 99%

Autophagy plays an important role in stemness mediation and the novel dual function of EIG121 in both autophagy and stemness regulation of endometrial carcinoma JEC cells

Ran

Zhou

Zhang

2017

International Journal of Oncology

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Endometrial cancer (EC) is the third most common gynecologic malignancy in the world, and is considered a chemotherapy poor responding cancer. There are two underlying mechanisms on chemoresistance: the stemness of cancer stem cells (CSCs) and activation of pro-survival autophagy. It was found that autophagy is one of the main factors of cancer stem cell survival, multidrug resistance and maintenance of the homeostasis of cancer stem cells and normal cancer cells. However, the relationship between CSCs and autophagy of EC cells is still unknown. In this study, higher autophagy level was found in endometrial cancer stem cells (ECSCs) and stemness kept in line with autophagy in successive cultured JEC spheres. Autophagy inhibition decreased the properties of CSCs in JEC spheres and enhanced sensitivity of ECSCs to paclitaxel. Besides, it was found that EIG121 exerted dual functions in the regulation of autophagy and stemness not only in normal JEC cells but also JEC obtained CSCs. These findings could be useful for developing targeted therapies for endometrial carcinoma.

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“…The initiation and regulation of autophagy signaling are described in Figure 1. Recent research has emphasized the important role of autophagy in cancer cell adaptability, growth, and survival in the tumor microenvironment (Lei et al, 2017). Autophagy has dual roles in cancer cells, including tumor-stimulating as well as tumor-suppressive functions (Avalos et al, 2014), with a wide range of effects on tumor progression and oncogenesis (Avalos et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Molecular Insights Into Therapeutic Potential of Autophagy Modulation by Natural Products for Cancer Stem Cells

Rahman

Saha

Rahman

et al. 2020

Front. Cell Dev. Biol.

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Autophagy, a cellular self-digestion process that is activated in response to stress, has a functional role in tumor formation and progression. Cancer stem cells (CSCs) accounting for a minor proportion of total cancer cells-have distinct self-renewal and differentiation abilities and promote metastasis. Researchers have shown that a numeral number of natural products using traditional experimental methods have been revealed to target CSCs. However, the specific role of autophagy with respect to CSCs and tumorigenesis using natural products are still unknown. Currently, CSCs are considered to be one of the causative reasons underlying the failure of anticancer treatment as a result of tumor recurrence, metastasis, and chemo-or radio-resistance. Autophagy may play a dual role in CSC-related resistance to anticancer treatment; it is responsible for cell fate determination and the targeted degradation of transcription factors via growth arrest. It has been established that autophagy promotes drug resistance, dormancy, and stemness and maintenance of CSCs. Surprisingly, numerous studies have also suggested that autophagy can facilitate the loss of stemness in CSCs. Here, we review current progress in research related to the multifaceted connections between autophagy modulation and CSCs control using natural products. Overall, we emphasize the importance of understanding the role of autophagy in the maintenance of different CSCs and implications of this connection for the development of new strategies for cancer treatment targeting natural products.

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Targeting autophagy in cancer stem cells as an anticancer therapy

Cited by 95 publications

References 73 publications

Quinoline‐Conjugated Ruthenacarboranes: Toward Hybrid Drugs with a Dual Mode of Action

Quinoline‐Conjugated Ruthenacarboranes: Toward Hybrid Drugs with a Dual Mode of Action

Autophagy plays an important role in stemness mediation and the novel dual function of EIG121 in both autophagy and stemness regulation of endometrial carcinoma JEC cells

Molecular Insights Into Therapeutic Potential of Autophagy Modulation by Natural Products for Cancer Stem Cells

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