By Melvin Li ’20

Glioblastomas are among the most malignant brain tumors. People diagnosed with them, typically do not have many options for treatment due to the tumors’ abilities to resist apoptosis, or cell death. The tumors tend to grow quickly and are very aggressive; due to the amount of blood supplied to the brain, tumor cells get ample nutrients and growth factors to proliferate. Patients are trypically treated via chemotherapy and radiotherapy, which damage healthy cells.

Recently, researchers in Beijing from the China Academy of Chinese Medical Sciences have studied potential alternatives. They investigated the anti-tumorigenic effects of sinomenine hydrochloride (SH) by culturing U87 and SF767 glioblastoma cell lines and exposing them to SH to test for autophagic activity and the presence of a marker for autophagy (LC3B-II). Autophagy is the degradation of cellular components that occurs in the cytoplasm of cells, and the components are broken down by lysosomes.

The researchers found that SH inhibited glioblastoma growth through autophagy by stimulating the production of reactive oxygen species (ROS). The accumulation of ROS could cause oxidative stress and DNA damage that signal glioblastoma cells to die. In addition, SH hindered cancer growth through the inhibition of the Akt-mTOR pathway. The experiments showed that SH reduced phosphorylation of mTOR and Akt while increasing LC3B-II in U87 and SF767 cells. To further test this, the researchers reversed the inhibition of the Akt-mTOR pathway using an Akt activator IGF-1, and showed that LC3B-II levels in the cells decreased, indicating that Akt-mTOR pathway inhibition is correlated with SH treatment.

Overall, this study showed that sinomenine hydrochloride can trigger cell mechanisms that lead to cell death through autophagy. This method could potentially eliminate fatal brain tumors while using fewer chemotherapeutic toxins, reducing damage to healthy human cells.

References:

1. “Glioblastoma (GBM).” Glioblastoma (GBM) | American Brain Tumor Association, http://www.abta.org/brain-tumor-information/types-of-tumors/glioblastoma.html?referrer.
2. Y. Jiang, et. al., Sinomenine hydrochloride inhibits human glioblastoma cell growth through reactive oxygen species generation and autophagy-lysosome pathway activation: an in vitro and in vivo study. International Journal of Molecular Sciences. 18, 19-45 (2017) doi:10.3390/ijms18091945.
3. Image retrieved from: https://commons.wikimedia.org/wiki/File:Glioblastoma_GFAP.jp