Systematic review on Ganoderma lucidum and its nanoparticles in oral cancer: Cytotoxicity, apoptosis and immunomodulation

Oral cancer carries high morbidity and mortality, yet although many studies have tested Ganoderma extracts, the evidence remains scattered. This study reviewed six years of literature on Ganoderma lucidum (GL) and its nanoparticles (GLNP) for evaluating the impacts of cytotoxicity, apoptosis and immunomodulation on oral cancer. A total of 67 studies of Science Direct (20), Web of Science (12), Scopus (30) and PubMed (5) were retrieved from 447 articles from the electronic databases. Among these 33 studies focused on GLNP, demonstrating significant cytotoxic effects against oral cancer cells. Additionally, 60 studies examined GL’s active compounds, particularly triterpenoids and polysaccharides, which exhibited anticancer and immunomodulatory properties. The quality of the included studies was evaluated using a modified risk assessment framework. The results showed that in-vitro studies demonstrated the highest quality, with 66% (40 articles) rated as good, 16% (10 articles) as fair, and 18% (11 articles) as poor. Followed by in-vivo studies with 53% (27 articles) rated as good, 33% (17 articles) as fair, and 14% (7 articles) as poor. In contrast, clinical trials showed the lowest quality, with only 22% (2 articles) rated as good, 33% (3 articles) as fair, and 45% (4 articles) as poor. The combined evidences indicate that GL and GLNP can induce apoptosis, suppress tumour growth, and boost immune responses. Nanoparticle delivery further enhances these effects by improving bioavailability and targeted delivery. However, well-designed studies are still required to confirm their true therapeutic value and clarify their clinical role as adjunct or alternative options for oral cancer.