Autophagy inhibition potentiates SAHA ‑mediated apoptosis in glioblastoma cells by accumulation of damaged mitochondria.

Autophagy inhibition potentiates SAHA‑mediated apoptosis in glioblastoma cells by accumulation of damaged mitochondria. Oncol Rep. 2018 Apr 16;: Authors: Lohitesh K, Saini H, Srivastava A, Mukherjee S, Roy A, Chowdhury R Abstract Glioblastoma multiforme (GBM), often referred to as a grade IV astrocytoma, is the most invasive type of tumor arising from glial cells. The main treatment options for GBM include surgery, radiation and chemotherapy. However, these treatments tend to be only palliative rather than curative. Poor prognosis of GBM is due to its marked resistance to standard therapy. Currently, temozolomide (TMZ), an alkylating agent is used for treatment of GBM. However, GBM cells can repair TMZ‑induced DNA damage and therefore diminish the therapeutic efficacy of TMZ. The potential to evade apoptosis by GBM cells accentuates the need to target the non‑apoptotic pathway and/or inhibition of pro‑survival strategies that contribute to its high resistance to conventional therapies. In recent studies, it has been demonstrated that HDAC inhibitors, such as vorinostat (suberoyl anilide hydroxamic acid; SAHA) can induce autophagy in cancer cells, thereby stimulating autophagosome formation. In addition, a lysosomotropic agent such as chloroquine (CQ) can result in hyper‑accumulation of autophagic vacuoles by inhibiting autophagosome‑lysosome fusion, which can drive the cell towards apoptosis. Hence, we postulated that co...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research