Elucidating the synergistic proteogenomic anticancer mechanisms of lentinan from Shiitake mushroom towards Temozolomide in human glioblastoma

Conventional chemotherapeutic agent, temozolomide (TMZ), for Glioblastoma (GBM) often displays high chemoresistance with various side effects. Additionally, extensive surgical resection is difficult and possesses a high risk to GBM patients, due to the invasive properties of tumors, especially around the cognitive areas of the brain. The therapeutic course is further complicated when GBM tumor cells acquire resistance, where the majority of the patients develop a high rate of tumor recurrence. Furthermore, multiple genetic changes and the high tumor heterogeneity of GBM indicate that a single drug is insufficient to provide an effective and complete solution to the problem. A multimodal treatment can work efficiently by sensitizing cancer cell DNA by one agent to other agents' anticancer effects. Therefore, multimodal treatment approaches incorporating multitarget natural products towards TMZ could offer an effective strategy against GBM, to enhance the anticancer effect on GBM cells. Our preliminary data has shown significant synergistic anticancer promotion of lentinan from Shiitake mushroom, towards TMZ, in one human GBM cell line. However, the comprehensive cellular and molecular synergistic mechanisms of lentinan in different human GBMs with different TMZ sensitivity remain unexplored. This project's general objective is to establish the commercial value of lentinan from Shiitake mushroom as a nutraceutical agent for human glioblastoma by elucidating its synergistic anticancer mechanisms with Temozolomide (TMZ) in human glioblastoma with different TMZ sensitivity. Although natural products demonstrate diverse pharmacological activities that serve as vital sources for anti-cancer drugs, their commercial health benefits are undervalued. Therefore, the in-depth cellular and molecular studies of lentinan may accentuate its commercial medicinal to be developed as a potential nutraceutical agent for GBM.