Ganoderma lucidum polysaccharide enhances radiosensitivity of hepatocellular carcinoma cell line HepG2 through Akt signaling pathway

Abstract

Ganoderma lucidum polysaccharide (GLP) is a well-known traditional Chinese medicine, known for its anti-cancer and immunomodulatory properties. The present study aims to investigate whether GLP has a therapeutic effect on hepatocellular carcinoma (HCC) cells exposed to radiation. Immunofluorescence was used to detect the nuclei, the protein expression was measured by western blot analysis and flow cytometry was used to detect the rate of cell apoptosis. GLP treatment was demonstrated to enhance radiation-induced growth inhibition and apoptotic death of HCC cells. At a molecular level, GLP suppressed the activities of DNA repair-associated proteins including ataxia-telangiectasia mutated (ATM) and DNA dependent-protein kinase (DNA-PK) in liver cancer cells under radiation conditions. Furthermore, the addition of an Akt inhibitor elevated the activities of DNA-PK and ATM and attenuated the GLP-induced HepG2 cell injury under the radiation condition. In conclusion, the present study demonstrates that GLP enhances the radiosensitivity of HCC cells via the regulation of Akt signaling pathways, implying a potential therapeutic effect of GLP as a radiation sensitizer in HCC treatment.

The Phytochemistry of Ganoderma Species and their Medicinal Potentials

“…The triterpenes act as anti-oxidants by scavenging free radicals and activating anti-oxidant enzymes, whereas polysaccharides reduce oxidative damage caused by reactive oxygen species and prevent the breaks of DNA strands (Kao et al, 2013). G. lucidum extracts are carcinostatic in a variety of cancer cell lines, including pancreatic, lung, colon, skin, breast, prostate, and liver cancer cell lines (Suprasert, 2015;Yu et al, 2017;Zhang, 2017). Furthermore, the compounds from G. lucidium (Xu et al, 2011) and G. applanatum have been shown to exhibit immunomodulatory, anti-angiogenic, and cytotoxic properties (Elkhateeb et al, 2018).…”

Research Progress on the Anticancer Activities and Mechanisms of Polysaccharides From Ganoderma

“…Targeting DNA repair pathways could enhance cancer cell sensitiveness to anticancer therapies and is a potential therapeutic option for cancer intervention. G. lucidum polysaccharide (GLP) was shown to augment radiation-mediated growth inhibition and apoptosis promotion in hepatocellular carcinoma (HCC) ( Yu et al, 2017 ). As one of mainstream anticancer regimens, radiation can induce cancer cell death by triggering DNA damage ( Li LY.…”

“…Ataxia-telangiectasia mutated (ATM) and DNA dependent-protein kinase (DNA-PK) are responsible for the repair of radiation-induced DNA lesions and double-strand break (DSB) ( Bannik et al, 2021 ). GLP impaired the DNA damage repair pathway in radiation-treated HCC cells by restraining the function of ATM and DNA-PK ( Yu et al, 2017 ). The protein kinase B (Akt) signaling pathway is involved in DNA damage repair ( Alemi et al, 2022 ).…”

What Chinese Medicine Can Do for Liver Cancer?

“…Ganoderma lucidum polysaccharide (GLP) is well known for its various pharmacologic properties including antitumor effects [52]. A study recently demonstrated that GLP treatment may augment growth inhibition and apoptotic death of HepG2 cells, which induced by radiation, and revealed the regulatory role of Akt signaling pathway for GLP-mediated radiosensitivity in HCC cells exposed to radiation [83].…”