Open AccessA new gamboge derivative Compound 2 inhibits cancer stem‐like cells via suppressing EGFR tyrosine phosphorylation in head and neck squamous cell carcinoma
Author(s) -
Deng Rongxin,
Wang Xu,
Liu Yang,
Yan Ming,
Hanada Sayaka,
Xu Qin,
Zhang Jianjun,
Han Zeguang,
Chen Wantao,
Zhang Ping
Publication year - 2013
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12129
Subject(s) - cancer stem cell , cancer research , head and neck squamous cell carcinoma , cancer , cancer cell , stem cell , protein kinase b , egfr inhibitors , epidermal growth factor receptor , biology , medicine , head and neck cancer , phosphorylation , microbiology and biotechnology
Cancer stem‐like cells represent a population of tumour‐initiating cells that lead to the relapse and metastasis of cancer. Conventional anti‐cancer therapeutic drugs are usually ineffective in eliminating the cancer stem‐like cells. Therefore, new drugs or therapeutic methods effectively targeting cancer stem‐like cells are in urgent need to successfully cure cancer. Gamboge is a natural anti‐cancer medicine whose pharmacological effects are different from those of conventional chemotherapeutical drugs and they can kill some kinds of cancer cells selectively. In this study, we identified a new gamboge derivative, Compound 2 (C2), which presents eminent suppression effects on cancer cells. Interestingly, when compared with cisplatin ( CDDP ), C2 effectively suppresses the growth of both cancer stem‐like cells and non‐cancer stem‐like cells derived from head and neck squamous cell carcinoma ( HNSCC ), inhibiting the formation of tumour spheres and colony in vitro , resulting in the loss of expression of multiple cancer stem cell ( CSC )‐related molecules in HNSCC . Treating with C2 effectively inhibited the growth of HNSCC in BALB /C nude mice. Further investigation found that C2 notably inhibits the activation of epithelial growth factor receptor and the phosphorylation of its downstream protein kinase homo sapiens v‐akt murine thymoma viral oncogene homolog (AKT) in HNSCC , resulting in down‐regulation of multiple CSC ‐related molecules in HNSCC . Our study has demonstrated that C2 effectively inhibits the stem‐like property of cancer stem‐like cells in HNSCC and may be a hopeful targeting drug in cancer therapy.