Glioblastoma (GB), a World Health Organization Grade IV (most lethal) astrocytoma , is the most common and aggressive primary brain tumor. GB’s lethality is a result of its recurrence after the use of conventional treatments such as chemotherapy and radiation therapy, and its ability to spread quickly through the use of tentacle-like structures. The recurrence is attributed to the presence of untreatable cancer stem cells (CSCs) within the tumor. The “stemness” of GB can be measured through the use of Nestin, a bona fide, or authentic marker of stem cells and differentiation. GB tumorigenesis is associated with aberrant functioning of the PI3K/mTOR signaling pathway, which regulates several cellular functions such as growth, proliferation, and migration. The mTOR (Mechanistic/ mammalian target of Rapamycin) pathway forms two functionally distinct multiprotein complexes, mTORC1 and mTORC2. Rapamycin (RAPA) is a natural compound found in the soil on Rapa Nui, and previous studies have shown that it strongly inhibits the mTORC1 complex. However, GB clinical trials have shown that RAPA is an incomplete inhibitor of the mTOR pathway. This prompted the discovery of novel small-molecule inhibitors, such as PP242, which appears to be more effective in treatment of GB because it inhibits both mTOR complexes. Naturally occurring compounds, Honokiol and Resveratrol may act synergistically with RAPA to target the GB CSCs. Honokiol, found in the bark, petals, and cones of the Magnolia tree, is a ligand which was used in ancient Chinese and Japanese medicine. Resveratrol, predominantly found in red grapes, is a stilbenoid compound, which has been shown to have anti-tumor properties. Previous studies have demonstrated that Honokiol moderately affects the mTOR pathway, and that Resveratrol has a protective effect against GB, however its role in regulating the mTOR pathway in GB is not well-defined. Therefore, I aim to target self-renewal and proliferation of CSCs using naturally occurring compounds with and without RAPA or PP242 via the mTOR pathway. I also plan to examine the levels of the stem cell marker, Nestin, before and after treatment with the aforementioned compounds, in order to measure the stemness of CSCs.