sinomenine and Glioblastoma

Topics: Antineoplastic Agents; Brain Neoplasms; Cell Line, Tumor; Cell Movement; Epithelial-Mesenchymal Transition; Glioblastoma; Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Morphinans

Glioblastoma is the most common malignant primary brain tumor, and it is one of the causes of cancer fatality in both adult and pediatric populations. Patients with glioblastoma require chemotherapy after surgical resection and radiotherapy. Therefore, chemotherapy constitutes a viable approach for the eradication of glioblastoma cells. In this study, the anti-tumor activity of sinomenine hydrochloride (SH) was evaluated in U87 and SF767 cells in vitro and in vivo. The results showed that SH potently inhibited U87 and SF767 cell viability and did not cause caspase-dependent cell death, as demonstrated by the absence of significant early apoptosis and caspase-3 cleavage. Instead, SH activated an autophagy-mediated cell death pathway, as indicated by the accumulated microtubule-associated protein light chain 3B (LC3B)-II, triggered autophagic flux and enhanced cell viability after pretreatment with autophagy inhibitors. SH-mediated autophagy in the two cell lines was implicated in reactive oxygen species (ROS) generation, protein kinase B (Akt)-mammalian target of rapamycin (mTOR) pathway suppression and c-Jun NH2-terminal kinase (JNK) pathway activation. The ROS antioxidant

Topics: Animals; Antineoplastic Agents; Apoptosis; Autophagy; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Brain Neoplasms; Cell Line, Tumor; Glioblastoma; Humans; JNK Mitogen-Activated Protein Kinases; Lysosomes; Male; Mice; Mice, Inbred BALB C; Microtubule-Associated Proteins; Morphinans; Reactive Oxygen Species; TOR Serine-Threonine Kinases