Abstract 3284: An in vitro synergism between Ganoderma lucidum and Bacillus Calmette Guérin on premalignant transitional cell carcinoma.

Abstract

Abstract Introduction: The major challenge for superficial transitional cell carcinoma (TCC) of the urinary bladder is recurrence. In the past three decades, Bacillus Calmette Guérin (BCG) has been used as an effective adjuvant therapy through the eradication of residual adverse cells following the surgical ablation of TCC tumors. Despite BCG has recently suspended for manufacture and shortage in supply, it provides moderate efficacy by reducing 30-40% of the recurrence cases but has high side effects toll of allergic cystitis. A medicinal mushroom - Ganoderma lucidum (GL) is known for its un-disputed scientific evidences which supporting the therapeutic roles on different cancers including TCC. In our previous reports, the triterpene-enriched ethanol extract of GL (GLe) was found to have similar immunological activities with BCG, in addition to apoptosis and telomerase inhibition. Therefore, BCG and GLe synergism was investigated. Brief Methodologies: The drug-drug interactions between BCG and GLe were assessed in an established carcinogen-sensitive human uroepithelial cell (HUC-PC) line, using two treatment schedules, i.e. co-treatment and pre-treatment with GLe. Outcome measures were cytoxicity and cytokines secretion using automated Vi-CELL cell viability analyzer (Beckman Coulter, USA) and FlowCytomix method (Bender MedSystems, Austria) with flow cytometry, respectively. Treated cells and culture media were harvested for measurements at 24 hours and 5 days upon the completion of the treatment schedules. Results and Discussion: In comparison with BCG, GLe was shown to exhibit immediate cytotoxic effects on the HUC-PC cells following incubation, whereas both drugs were individually active in stimulating the production of interleukin (IL)-6, IL-8 and monocyte chemotactic protin-1 (MCP-1). In both treatment schedules, complete cytostasis by maintaining the baseline cell seeding numbers was demonstrated in 24 hours, and cell eradication processes were progressively executed in the next 5 days in dose-dependent manners. By isobologram analysis, the interaction between BCG and GLe on cytotoxicity was shown to be synergistic. However, the pre-treatment of GLe has also resulted in suppression of all cytokines without influencing its cytotoxic effect. Conclusion: The results suggested that pre-treatment of GLe before BCG incubation could be effective to enhance the efficacy in adverse cells eradication, and potentially useful for counteracting the inflammation-associated side effects. Citation Format: John W. Yuen, Mayur-Danny I. Gohel, Chi-Fai Ng. An in vitro synergism between Ganoderma lucidum and Bacillus Calmette Guérin on premalignant transitional cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3284. doi:10.1158/1538-7445.AM2013-3284