Prof. HUANG Qing’s group from Hefei Institutes of Physical Science reported ganoderic acid,which is important bioactive component of “Lingzhi”, induced synergistic autophagic cell death except for apoptosis in esophageal squamous cell carcinoma (ESCC) cells.

In this study, the researchers confirmed that ganoderic acids could inhibit cell proliferation and induce both apoptosis and autophagic cell death.

In particular, they found that in the early stage of the autophagic process, ganoderic acid D could initiate and enhance the autophagy signal, while in the late stage it could block the autophagic flux on the contrary by impairing the autophagosome-lysosome fusion and inhibiting the lysosomal degradation.

Besides the autophagic cell death, it also induced the apoptosis mediated by caspase-related process in parallel.

Furthermore, The team took a closer look at the molecular level, and found that ganoderic acid D could down-regulate the expression of PI3K, AKT and mTOR phosphorylated proteins in the mTOR signaling pathway which thus led to the synergistic effect on apoptosis and autophagic cell death in the ESCC cells.

Ganoderma lucidum (G.lucidum, also called " Lingzhi" in China) has been recognized as a traditional Chinese herbal mushroom for thousands of years, and has many medicinal functions. Ganoderic acids plays important role in G. lucidum and have cytotoxicity to many tumor cells. However, the mechanism involved in its anticancer cell process is still largely elusive.

The findings from this study not only reveals the mechanism of ganoderic acids for inducing synergistic apoptosis and autophagic cell death by disrupting the autophagic flux, but also may open up the new perspective of cancer therapy using Ganoderma lucidum as an effective anti-cancer adjuvant.

The research was mainly supported by the National Natural Science Foundation of China (grants No. 11635013 and No. 11775272) and Central-level scientific institutions repair and purchase special funds (No. Y79XG13361).

Link to the paper: Ganoderic acid D induces synergistic autophagic cell death except for apoptosis in ESCC cells.

The mechanism and process of the ganoderic acid D (GAD)-induced apoptosis and autophagic cell death in the ESCC cells. a) The mechanism and pathways of GAD induced autophagic cell death and apoptosis in ESCC cells. b) The involved process for the GAD-induced autophagic cell death. (Image by SHAO Changsheng)