Antrodia camphorata is a unique mushroom of Taiwan, which has been used as a traditional medicine for protection of diverse health‐related conditions. In an effort to translate this Eastern medicine into Western‐accepted therapy, a great deal of work has been carried out on A. camphorata. This review discusses the biological activities of the crude extracts and the main bioactive compounds of A. camphorata. The list of bioactivities of crude extracts is huge, ranging from anti‐cancer to vasorelaxation and others. Over 78 compounds consisting of terpenoids, benzenoids, lignans, benzoquinone derivatives, succinic and maleic derivatives, in addition to polysaccharides have been identified. Many of these compounds were evaluated for biological activity. Many activities of crude extracts and pure compounds of A. camphorata against some major diseases of our time, and thus, a current review is of great importance. It is concluded that A. camphorata can be considered as an efficient alternative phytotherapeutic agent or a synergizer in the treatment of cancer and other immune‐related diseases. However, clinical trails of human on A. camphorata extracts are limited and those of pure compounds are absent. The next step is to produce some medicines from A. camphorata, however, the production may be hampered by problems related to mass production.

Oral squamous cell carcinoma (OSCC) is among the most commonly diagnosed malignancies in the world. Patients with OSCC often develop treatment resistance, resulting in a poor prognosis. Mounting evidence indicates that interactions between cancerous cells and other components of the tumor microenvironment (TME) determine their response to treatment. Herein, we examined the role of cancer stem cell-derived extracellular vesicles (CSC_EVs) generated from CAL27 and SCC-15 OSCC cells in the development of cisplatin (CDDP) resistance. We demonstrated that CSC_EVs enhance CDDP resistance, clonogenicity, and the tumorsphere formation potential of OSCC cells. Our bioinformatics analyses revealed that OSCC_EVs are enriched with microRNA (miR)-21-5p and are associated with increased metastasis, stemness, chemoresistance, and poor survival in patients with OSCC. Mechanistically, enhanced activity of CSC_EVs was positively correlated with upregulated β-catenin, phosphatidylinositol-3 kinase (PI3K), signal transducer and activator of transcription 3 (STAT3), mammalian target of rapamycin (mTOR), and transforming growth factor (TGF)-β1 messenger (m)RNA and protein expression levels. CSC_EVs also conferred a cancer-associated fibroblast (CAF) phenotype on normal gingival fibroblasts (NGFs), with the resultant CAFs enhancing the oncogenicity of OSCC cells. Interestingly, treatment with ovatodiolide (OV), the bioactive component of Anisomeles indica, suppressed OSCC tumorigenesis by reducing the cargo content of EVs derived from CSCs, suppressing self-renewal, and inhibiting the NGF-CAF transformation by disrupting EV-TME interactions. Moreover, by suppressing miR-21-5p, STAT3, and mTOR expressions in CSC_EVs, OV re-sensitized CSCs to CDDP and suppressed OSCC tumorigenesis. In vivo, treatment with OV alone or in combination with CDDP significantly reduced the tumor sphere-forming ability and decreased EV cargos containing mTOR, PI3K, STAT3, β-catenin, and miR-21-5p. In summary, our findings provide further strong evidence of OV’s therapeutic effect in OSCC.

Lung cancer is the leading cause of cancer deaths worldwide and current therapies fail to treat this disease in majority of cases. Antrodia camphorata is a medicinal mushroom being widely used as food dietary supplement for cancer prevention. The sesquiterpene lactone antrocin is the most potent among >100 secondary metabolites isolated from A. camphorata . However, the molecular mechanisms of antrocin-mediated anticancer effects remain unclear. In this study, we found that antrocin inhibited cell proliferation in two non-small-cell lung cancer cells, namely H441 (wild-type epidermal growth factor receptor, IC ₅₀ = 0.75 μM) and H1975 (gefitnib-resistant mutant T790M, IC ₅₀ = 0.83 μM). Antrocin dose dependently suppressed colony formation and induced apoptosis as evidenced by activated caspase-3 and increased Bax/Bcl2 ratio. Gene profiling studies indicated that antrocin downregulated Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. We further demonstrated that antrocin suppressed both constitutively activated and interleukin 6-induced STAT3 phosphorylation and its subsequent nuclear translocation. Such inhibition is found to be achieved through the suppression of JAK2 and interaction between STAT3 and extracellular signal-regulated kinase. Additionally, antrocin increased microRNA let-7c expression and suppressed STAT signaling. The combination of antrocin and JAK2/STAT3 gene silencing significantly increased apoptosis in H441 cells. Such dual interruption of JAK2 and STAT3 pathways also induced downregulation of antiapoptotic protein mcl-1 and increased caspase-3 expression. In vivo intraperitoneal administration of antrocin significantly suppressed the growth of lung cancer tumor xenografts. Our results indicate that antrocin may be a potential therapeutic agent for human lung cancer cells through constitutive inhibition of JAK2/STAT3 pathway.