Cordycepin Augments the Chemosensitivity of Human Glioma Cells to Temozolomide by Activating AMPK and Inhibiting the AKT Signaling Pathway.

Glioblastoma multiforme (GBM) is the most commonly encountered subtype of deadly brain cancer in human adults. It has a high recurrence rate and shows aggressive proliferation. The novel cytotoxic agent temozolomide (TMZ) is now frequently applied as the first-line chemotherapeutic treatment for GBM; however, a considerable number of patients treated with TMZ turn out to be refractory to this drug. Hence, a more effective therapeutic approach is urgently required to overcome this critical issue. Accumulating evidence has shown that both AMPK and AKT are activated by TMZ, while only AMPK contributes to apoptosis via mammalian target of rapamycin (mTOR) inhibition. Accordingly, AKT increases the tumorigenicity and chemoresistance of various tumor cells. In addition, AKT overexpression increases the resistance of glioma cells to TMZ. Cordycepin, a major bioactive component in Cordyceps militaris, exhibits immunomodulatory, anticancer, antioxidant, and anti-inflammatory activities, among other therapeutic eff...