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A potent indolylquinoline alleviates growth of human lung cancer cell tumorspheres

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Abstract

To fight cancer at its roots by targeting cancer stem cells is a promising approach for therapy. Previously, an indolylquinoline derivative, 3-((7-ethyl-1H-indol-3-yl)-methyl)-2-methylquinoline (EMMQ), was reported effectively inhibiting the growth of lung cancer cells through impairment of cellular mitochondria functions. To address more on drug efficiency, the study further exploited if EMMQ can impede the propagation of tumorspheres stemmed from non-small cell lung cancer cells. EMMQ inhibited proliferation of spheroids in culture. In animal models, administration of the drug attenuated the spheroid tumorigenicity. The activated apoptosis alleviated growth of xenograft tumors in immune-deficient mice as established by the enriched tumorspheres. More evidence suggested that the reduced stemness of the spheroid tumors is attributed to apoptotic death. The findings supported that EMMQ is an eligible approach to eradicate the minor but tumorigenic lung cancer tumorspheres.

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Abbreviations

ABCG2:

ATP-binding cassette subfamily G member 2

ALDH1A1:

Aldehyde dehydrogenase 1A1

BrdU:

Bromodeoxyuridine

BSA:

Bovine serum albumin

CSCs:

Cancer stem-like cells

DMSO:

Dimethyl sulfoxide

DAPI:

4′,6-diamidino-2-phenylindole

EMMQ:

3-((7-ethyl-1H-indol-3-yl)-methyl)-2-methylquinoline

FBS:

Fetal bovine serum

FITC:

Fluorescein isothiocyanate

NSCLC:

Non-small cell lung cancer

PARP:

Poly(adenosine diphosphate ribose) polymerase

PBS:

Phosphate-buffered saline

PCNA:

Proliferating cell nuclear antigen

TRITC:

Tetramethylrhodamine isocyanate

TUNEL:

Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling

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Acknowledgements

The work is supported in part by grants from Ministry of Science and Technology, Executive Yuan, Taiwan (MOST-103-2311-B-003-001-) and National Taiwan Normal University (102T3040B2, 103T3040D2 and 104T3040C2). We thank technical assistance of confocal laser microscopy from College of Life Science and Instrumentation Center, National Taiwan Normal University.

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Authors and Affiliations

  1. Department of Life Science, National Taiwan Normal University, 88 Ting-Chow Rd, Sec 4, Taipei, 116, Taiwan, Republic of China

    Yu-Ling Ni, Chang-Hung Hsieh, Seung-Hun Kim, Jing-Ping Wang & Kang Fang

  2. Department of Human Development and Family Studies, National Taiwan Normal University, Taipei, Taiwan, Republic of China

    Chun-Li Su

  3. Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan, Republic of China

    Ching-Fa Yao

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  1. Yu-Ling Ni
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Correspondence to Kang Fang.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Ni, YL., Hsieh, CH., Kim, SH. et al. A potent indolylquinoline alleviates growth of human lung cancer cell tumorspheres. Apoptosis 22, 1235–1245 (2017). https://doi.org/10.1007/s10495-017-1401-3

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