Cinnamaldehyde impacts key cellular signaling pathways for induction of programmed cell death in high-grade and low-grade human glioma cells

ObjectivePrimary tumors of the brain and a large percent of malignant brain tumors are gliomas. Gliomas comprise high-grade gliomas like glioblastoma multiforme (GBMs), many of which have mutation in the tumor suppressor p53 gene and low-grade gliomas (LGGs). LGGs can progress to GBMs due to various factors. The available treatment options for GBMs and LGGs include surgical resection, radiation and chemotherapy. The chemotherapeutic drug available in the clinic is temozolomide (TMZ). However, TMZ can cause damage to DNA if taken for prolonged period. This warrants the discovery of drugs that would potentially elicit less adverse side effects while maintaining anticancer activity. To this end, we evaluated the impact of cinnamaldehyde (CA), a single, purified component of the natural product cinnamon.ResultsThe elucidation of the mechanism of action revealed the impact of CA on reactive oxygen species (ROS) levels. Moreover, its effect on the extrinsic programmed cell death pathway resulted in the increase of apoptotic cell populations, invoking multicaspase. Notably, the cell survival/death pivotal molecule Bcl-2 was impacted. These effects were observed in both the types of brain tumor cells studied: GBMs, represented by U251 cells (p53 mutated cell line) and LGGs represented by H4 cells. Results from the current study suggest potential for CA as a therapeutic option as it is expected to have fewer adverse side effects due to it being a component of a natural product and possibly deter the progression of LGGs to GBMs.