Abstract #2673: Immunotherapeutic properties of Ganoderma lucidum on bladder carcinoma prophylaxis

Introduction: Ganoderma lucidum (GL) is a representative species of medicinal mushroom, which is used by many cancer patients as a supplement for prevention and/or recurrence of tumors. There are un-disputed scientific evidences supporting the therapeutic roles of GL on different cancers. High recurrence is regarded as the main challenge for superficial transitional cell carcinoma (TCC) of the urinary bladder. Polysaccharides and triterpenes are the key bioactive components responsible for anti-tumor properties. Conventionally, BCG immunotherapy is the most effective agent for preventing the recurrence. However, the mechanism by which BCG invokes its immunotherapy can be found in other molecules and we hypothesize that GL could be even more powerful than BCG, and become a new therapeutic modality for the bladder prophylaxis. Brief Methodologies: An established carcinogen-sensitive human uroepithelial cell (HUC-PC) line was used to evaluate the therapeutic potential of GL. The triterpene extract of GL (GLe) was incubated with the cells with or without 4-aminobiphenyl (ABP) pre-treatment. Cells were collected and analyzed for apoptosis using Annexin-V/7-AAD flow cytometric method, and extracted for measuring the activities of telomerase using RT real-time PCR and nuclear factor-kappa B (NF-\#954;B) using ELISA-EMSA. Cultured media were also harvested for measuring the secretion of interleukin-1\#946; (IL-1\#946;), IL-6 and chemotaxis potential. Results and Discussion: In the pre-cancerous HUC-PC cells, apoptosis was induced by GLe at micromolar levels. It was shown in previous publications that this is associated with the reduction of both basal and ABP-induced telomerase activities. At early stage, apoptotic cells express phosphatidylserine (PS) to facilitate the process of phagocytic clearance. Unpublished data indicates that harvested media from these apoptotic cells were chemotactic to neutrophils. In addition, secretion of pro-inflammatory cytokine IL-6 but not IL-1\#946; from the HUC-PC cells was enhanced by GLe, in dose-dependent manner, in parallel with the increase of NF-\#954;B activity. In comparison, BCG was also able to induce IL-6 production via the NF-\#954;B pathway, but could not trigger an apoptotic response. Conclusion: Conclusively, the results indicated that triterpene extract of GL is similar to BCG, which is immunological active, but it is more supreme such that, it can also induce telomerase-associated apoptosis, and therefore, eliminating the adverse pre-cancerous TCC cells which, under carcinogenic attack can become tumorigenic. This suggests the potential therapeutic properties of GL in the prophylaxis of bladder carcinoma.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2673.