A new gamboge derivative Compound 2 inhibits cancer stem‐like cells via suppressing EGFR tyrosine phosphorylation in head and neck squamous cell carcinoma

Abstract

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.

Targeting cancer stem cells in squamous cell carcinoma

“…Treatment with cetuximab also promotes differentiation of CSCs and impairs resistance of CSC to chemo/radiation 161 . Also, a newly discovered gamboge derivative compound 2 showed effective inhibition of HNSCC by targeting a CSC population through EGFR tyrosine phosphorylation 162 . However, another study has demonstrated that the EGFR-targeted agents, such as cetuximab and erlotinib, show only modest effects on tumor control of HNSCC 161 …”

Radioresistance in Head and Neck Squamous Cell Carcinoma — Possible Molecular Markers for Local Recurrence and New Putative Therapeutic Strategies

“…Interestingly, the Gamboge derivate Compound 2 (C2) is able to inhibit growth also in HNSCC stem cells. Indeed, it can inhibit formation of tumor spheres and repress the expression of multiples genes related to cancer stem cell phenotype by blocking the activation of EGFR pathways [132]. Since one of the main causes of failure in HNSCC treatment is the enrichment of CSCs population, which are resistant to current therapy, the future use of this molecule in combination with chemoradiotherapy could prevent the selective enrichment of CSCs after HNSCC conventional treatment.…”