A potent indolylquinoline alleviates growth of human lung cancer cell tumorspheres

• Published in: Apoptosis (London) 2017-10, Vol.22 (10), p.1235-1245
• Main Authors: Ni, Yu-Ling, Hsieh, Chang-Hung, Kim, Seung-Hun, Wang, Jing-Ping, Su, Chun-Li, Yao, Ching-Fa, Fang, Kang
• Format: Article
• Language: English
• Subjects: Analysis; Animal models; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; Apoptosis - drug effects; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Carcinogenesis - drug effects; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Cell Biology; Cell culture; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Ethylenediaminetetraacetic acid; Female; Growth; Humans; Indoles - pharmacology; Indoles - therapeutic use; Lung cancer; Lung cancer, Non-small cell; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Mice; Mice, Nude; Mitochondria; Mitochondria - drug effects; Neoplasm Transplantation; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - pathology; Neoplastic Stem Cells - transplantation; Non-small cell lung carcinoma; Oncology; Propagation; Quinolines - pharmacology; Quinolines - therapeutic use; Spheroids; Stem cell transplantation; Stem cells; Transplantation; Tumor Stem Cell Assay; Tumorigenicity; Tumors; Virology; Xenografts
• ISSN: 1360-8185; 1573-675X
• DOI: 10.1007/s10495-017-1401-3

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.