Artemisinin pre-treatment fore cisplatin dosage enhances high grade urothelial carcinoma treatment in male albino mice via reverse gene expression modulation of FGFR3, HRAS, P53 and KDM6A.

BACKGROUND: Urinary bladder cancer, is the 10th most common global cancer, diagnosed in over 600,000 people causing 200,000 deaths annually. Artemisinin and its derivatives are safe compounds that have recently been proven to possess potent anti-tumor effects in vivo, through inhibition of cancer cell growth. The aim of this study is to assess the efficiency of artemisinin as a cancer treatment alone and as a pre-treatment fore cisplatin therapy for high grade urothelial carcinoma. METHODS: Sixty male albino mice were divided into six groups, and BBN was used to induce urinary bladder cancer. Blood samples were tested for renal functions and complete blood counts, kidney and urinary bladder tissues were harvested for histopathological examination. Total RNAs from urinary bladder tissues was collected, and gene expression of FGFR3, HRAS, P53, and KDM6A was quantified using qRT-PCR. RESULTS: Compared to the induced cancer group, the results revealed that FGFR3 expression levels were down-regulated in the induced cancer group treated by artemisinin only and the induced cancer group pre-treated with artemisinin prior to cisplatin by ~ 0.86-fold and 0.4-folds, respectively, aligning with HRAS down-regulation by ~ 9.54-fold and 9.05-fold, respectively. Whereas, P53 expression levels were up-regulated by ~ 0.68-fold and 0.84-fold, respectively, in parallel with KDM6A expression, which is up-regulated by ~ 0.95-folds and 5.27-folds, respectively. Also, serum creatinine and urea levels decreased significantly in the induced cancer group treated by artemisinin alone and the induced cancer group pre-treated with artemisinin prior to cisplatin, whereas the induced cancer group treated by cisplatin their levels increased significantly. Moreover, Hb, PLT, RBC, and WBC counts improved in both cancer groups treated by artemisinin alone and pre-treated with artemisinin prior to cisplatin. Histologically, in kidney tissues, artemisinin pre-treatment significantly reduced renal injury caused by cisplatin. While Artemisinin treatment for cancer in bladder tissues reverted invasive urothelial carcinoma to moderate urothelial dysplasia. CONCLUSIONS: This study indicates that artemisinin demonstrated a significant effect in reversal of the multi-step carcinogenesis process of high grade urothelial carcinoma and could enhance the effect of cisplatin therapy using artemisinin pre-treatment.

Inhibition of TNF-α Oncogene Expression by Artemisia Annua L. Extract Against Pioglitazone Side Effects in Male Albino Mice.

Pioglitazone (Actos) is one of the most recent oral antidiabetic drugs for treating the second type of diabetes mellitus as a common chronic and lifelong disease, but with harmful side effects. The objective of this study is to evaluate the effectiveness of Artemisia annua L. extract against the Actos drug side effects in the male albino mice. In present study, the use of Actos drug alone induced hepatotoxicity, renal inflammation, hematological disorders and bladder cancer, which are manifested by biochemical abnormalities and histopathological changes, moreover, the severity of toxicity depends on its dose. In contrast, the concurrent treatment with both Actos drug (45 mg/kg) and Artemisia extract (4 g/kg) was effective against the harmful side effects of the Actos drug. Where, the biochemical, hematological and histopathological investigations showed that the hepatotoxicity, renal inflammation, hematological disorders and histopathological changes were improved using combination of Actos and Artemisia extract. In addition, the results of TNF-ɑ oncogene expression levels in bladder tissues were significantly decreased by about 99.99% using the mix of both Actos drug and Artemisia extract. In conclusion, these findings reveal that the Artemisia annua extract on TNF-ɑ oncogene expression level is very significant and effective natural product against harmful side effects of pioglitazone which associated with an increased risk of incident bladder cancer among people, but for application more studies must be achieved in that field.