Background: Cancer initiating cells (CICs) represent a rare subpopulation of cancer cells, which are responsible for tumor growth. Cancer initiating cells such as oral cancer-cancer initiating cells (OC-CICs), are often resistant to either radiotherapy or chemotherapy. Therefore, screening and development for drug candidates that target OC-CICs specifically will benefit for future oral cancer therapy.

Methods: First, we used the in vitro cell-based ALDH activity assay system, which has been demonstrated as a CICs marker, to screen for the active components from purified compounds of Antrodia Camphorata Mycelia extract (ACME), which can target OC-CICs. The growth inhibition and cell differentiation ability of OC-CICs treated with purified compounds from ACME were evaluated. In addition, the self-renewal ability and stemness properties of ACMEs treated OC-CICs were examined. Furthermore, xenotransplantation assay was applied to test the tumorigenicity of OC-CICs treated with isolated ACMEs. Finally, we investigated the molecular mechanisms mediated by ACME treatment on OC-CICs.

Results: Herein, we first found out that an ACME's purified components, CH-190-WS-D, significantly downregulated the ALDH activity of oral cancer cells. Treatment of CH-190-WS-D significantly induced cell death and enhanced the differentiation capability of OC-CICs but not the major population of oral cancer cells. Moreover, we found that treatment of CH-190-WS-D reduced the self-renewal ability and stemness properties of OC-CICs. The in vitro tumorigenic properties, including cell migration and anchorage independent growth of OC-CICs, were lessened by CH-190-WS-D treatment. Furthermore, treatment of CH-190-WS-D suppressed tumor growth of nude mice bearing xenografts. Finally, treatment of CH-190-WS-D results in down-regulation of PI3K/AKT/mTOR molecular mechanisms which play important roles in CICs.

Conclusion: Our studies reveal the ACME's purified components can reduce stemness properties and tumorigenicity of OC-CICs. Eventually, we can discover drug candidates from ACME's purified components for alternative oral cancer therapy.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4374. doi:10.1158/1538-7445.AM2011-4374

©2011 American Association for Cancer Research
2011