07/14/2021
Keio University School of Medicine
A research group led by Associate Professor Yasunari Kabe, Kazuyasu Koike (a second-year student in the Doctoral Programs at the Graduate School of Medicine), and Professor Makoto Suematsu of the Department of Biochemistry, Keio University School of Medicine, has discovered that glycyrrhizin (GL), the main component of licorice found in many Kampo medicines, and its derivatives bind to the heme-binding membrane protein PGRMC1, powerfully enhancing the effects of anticancer drugs.
The group has previously reported that PGRMC1 is highly expressed in various solid tumors and plays a crucial role in cancer cell proliferation and the acquisition of drug resistance. Although PGRMC1 has attracted attention as a target protein for cancer therapy, no substance that inhibits its function had been discovered. In this study, the researchers elucidated the molecular structure of GL's binding to PGRMC1. They also showed that GL suppresses the activation of the epidermal growth factor (EGF) signal and inhibits the uptake of low-density lipoprotein (LDL) cholesterol into the cell nucleus. Moreover, they revealed that it also suppresses cancer cell proliferation in a mouse cancer transplant model. They also discovered that glucoglycyrrhizin, a derivative of GL, more potently inhibits the function of PGRMC1 and suppresses cancer cell proliferation.
These results indicate that GL derivatives control the function of PGRMC1, which is abundant in cancer cells, and significantly enhance the effects of anticancer drugs. They are expected to be applied as new therapeutic agents for cancer.
The results of this research were published in the online preliminary report of the scientific journal "Cancers" on June 30, 2021 (UK time).
Please see below for the full press release.