ABSTRACT
Background: Despite several therapeutic options available for bladder cancer, the outcomes are less satisfactory. To find a more effective modality, we were interested in the bioactive mushroom extract, PDF, which has been shown to sensitize certain anticancer drugs. Accordingly, we investigated if cytotoxic effects of several anticancer drugs used on bladder cancer patients could be enhanced with PDF in vitro.Methods: Human bladder cancer T24 cells were treated with four anticancer drugs, carmustine (BCNU), 5-fluorouracil (5FU), cisplatin (CPL), and doxorubicin (DOX) alone, their combinations, or in combination with PDF, and cell viability was determined. To explore the anticancer mechanism, the status of glyoxalase I (Gly-I), an enzyme involved in the drug resistance of cancer cells, and oxidative stress that can cause severe cellular injury/damage was also assessed.Results: BCNU and 5FU alone resulted in a >50% reduction in cell viability but CPL and DOX had no such effects. Only a combination of BCNU and PDF led to a drastic (~90%) cell viability reduction, accompanied by inactivation of Gly-I and an increase in oxidative stress. However, any combinations of other drugs and PDF had little effects on cell viability, Gly-I activity, or severity of oxidative stress.Conclusions: This study shows that anticancer activity of BCNU is significantly potentiated with PDF in T24 cells. This is rather attributed to inactivated Gly-I and increased oxidative stress. Therefore, PDF appears to have a chemosensitizing effect capable of enhancing BCNU cytotoxicity, which may offer an alternative, improved therapeutic option for bladder cancer.
ABSTRACT
Aim: To describe a case of acute hepatic injury related to the use of Grifola frondosa in a patient with colon cancer. Case Presentation: Patient is a 67 year old female with stage IV poorly differentiated adenocarcinoma of the colon, who presented with epigastric pain one month after resection of her primary tumor. A staging PET scan revealed metastasis to regional lymph nodes without solid organ involvement. Her home medications include longstanding amlodipine and losartan, and a recently started Grifola frondosa derivative. Her laboratory data was significant only for acute transaminitis (AST:967 U/L, ALT:768 U/L) without hyperbilirubinemia. Alcohol, acetaminophen, and a viral panel (EBV, CMV, hepatitis A/B/C) were all negative. A CT scan revealed heterogenous liver parenchyma without focal lesions. A subsequent liver biopsy demonstrated active portal inflammation with eosinophilic infiltration. Discussion: The etiologies of significant acute transaminitis include viral hepatitis, ischemic liver injury, acetaminophen toxicity and drug-induced liver injury (DILI). Viral and ischemic hepatitis and acetaminophen toxicity were excluded based on laboratory analysis and imaging studies. Liver biopsy findings demonstrating the characteristic eosinophilic infiltration of a drug reaction favored DILI as the etiology of transaminitis in this case. With a RUCAM score of 7 calculated based on history, clinical course, and objective data, DILI was concluded to be probably attributed to the patient’s recent use of the Grifola frondosa extract. Conclusion: A diagnosis of drug induced liver injury probably secondary to the use of Grifola frondosa extract was made after excluding all other causes of significant acute transaminitis.