Abstract
Abstract Background: Cancer stem cells (CSCs), also termed as Cancer initiating cells (CICs), represent a rare subpopulation of cells, which are responsible for tumor growth. CICs such as oral cancer -cancer initiating cells (OC-CICs), are often resistant to either radio- or chemotherapy. Therefore, development of drug candidates that specifically target OC-CICs will be effective for future oral cancer therapy. Methods: In this study, we used the in vitro cell-based ALDH activity assay system, which has been demonstrated as a CICs marker, to screen for the active purified components from Antrodia Cinnamomea Mycelia extract (ACME), which can target OC-CICs. In combination with the active components from ACME that targeting OC-CICs, we evaluated the synergistic effect of above active components from ACMS on target oral cancer stem cells. Results: We first found ACME purified compounds (CH-190-WS-A and CH-190-WS-D) can significantly down regulate the ALDH activity of oral cancer cells or OC-CICs, respectively. Treatment of CH-190-WS-A and CH-190-WS-D significantly induced cell death and enhanced the differentiation capability of OC-CICs. Moreover, we found that treatment of CH-190-WS-A and CH-190-WS-D reduced the self-renewal ability, tumorigenic properties and stemness properties of OC-CICs in vitro. Additionally, treatment with CH-190-WS-A or CH-190-WS-D suppressed tumor growth of nude mice bearing tumor xenografts, respectively. Furthermore, treatment of CH-190-WS-D results in down-regulation of mTOR/PI3K/pAKT molecular mechanisms which play an important role in CICs. Whereas treatment of CH-190-WS-A inactivated Notch pathway, which can restore AKT activity then overcome cell death. Finally, combined treatment of CH-190-WS-D and CH-190-WS-A also dramatically caused cell death of OC-CICs through dual-pathway blockage. Conclusion: Our studies reveal combination of ACME purified components can target OC-CICs. Eventually, we can develop therapeutic protocol for alternative oral cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3385A. doi:1538-7445.AM2012-3385A
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