Department of Pharmacology, Medical School of Soochow University, Suzhou, China.
Cancer Sci. 2012 Apr;103(4):684-90. doi: 10.1111/j.1349-7006.2011.02198.x. Epub 2012 Jan 30.
Glioblastoma (GBM) is a highly aggressive brain tumor characterized by increased proliferation and resistance to chemotherapy and radiotherapy. Recently, a growing body of evidence suggests that glioma-initiating cells (GICs) are responsible for the initiation and recurrence of GBM. However, the factors determining the differential development of GICs remain poorly defined. In the present study, we show that curcumin, a natural compound with low toxicity in normal cells, significantly induced differentiation of GICs in vivo and in vitro by inducing autophagy. Moreover, curcumin also suppressed tumor formation on intracranial GICs implantation into mice. Our results suggest that autophagy plays an essential role in the regulation of GIC self-renewal, differentiation, and tumorigenic potential, suggesting autophagy could be a promising therapeutic target in a subset of glioblastomas. This is the first evidence that curcumin has differentiating and tumor-suppressing actions on GICs.
胶质母细胞瘤（GBM）是一种高度侵袭性的脑肿瘤，其特征是增殖增加，对化疗和放疗具有抗性。最近，越来越多的证据表明，神经胶质瘤起始细胞（GICs）是 GBM 发生和复发的根源。然而，决定 GIC 分化的因素仍未得到明确界定。在本研究中，我们发现姜黄素，一种在正常细胞中具有低毒性的天然化合物，通过诱导自噬，显著地诱导体内和体外 GIC 的分化。此外，姜黄素还抑制了将 GIC 颅内植入到小鼠体内后肿瘤的形成。我们的结果表明，自噬在 GIC 自我更新、分化和致瘤潜能的调控中起着至关重要的作用，这提示自噬可能是某些胶质母细胞瘤的一种有前途的治疗靶点。这是首次证明姜黄素对 GIC 具有分化和抑瘤作用的证据。
