Comparison of anti-cancer effects of platinum ribavirin and ribavirin via telomerase and Bcl-2 gene expression.

Among the common treatments for cancers, chemotherapy is widely used. One of the ways to evaluate the effectiveness of anti-cancer drugs is by checking the expression of tumor markers. Hence, this study aimed to evaluate the anti-cancer effects of the newly synthesized platinum ribavirin (Pt-Rb) compared to ribavirin (Rb) through biomarkers. In this study, cell lines were divided into four groups: groups A and B as healthy negative control group and untreated cancer group respectively. Group C and D were treated with, Rb and Pt-Rb, a novel anti-cancer drug, respectively. After evaluating LC50 for the drugs by MTT test, the expression of telomerase and Bcl-2 (B cell lymphoma-2) genes was evaluated using real-time PCR (RT-qPCR). The results showed a significant decrease in telomerase (0.020 ± 0.007) and Bcl-2(0.120 ± 0.005) gene expression in cancer cells treated with Pt-Rb (group D) compared to telomerase (0.040 ± 0.014) and Bcl-2(0.220 ± 0.014) treated with Rb (group C) and also between group D and telomerase (70.76 ± 0.330) and Bcl-2 (99.52 ± 0.670) in group B. The majority of the groups under investigation showed a significant difference (p < 0.05), suggesting that Pt-Rb had stronger anti-cancer effects than Rb and untreated cancer cells. Additionally, Pt-Rb treatment results demonstrated more increased apoptosis than Rb. Our results demonstrated that Pt-Rb is an effective medication in cancer treatment by lowering anti-apoptotic indicators. Therefore, this chemical has the potential to be an effective anti-cancer therapy, pending further research on animal models and then human volunteers.

Study of anticancer effects of platinum levetiracetam and levetiracetam via cancer biomarkers genes expression on HepG2 cell line.

BACKGROUND: High expression of some anticancer biomarkers such as telomerase and B cell lymphoma-2(Bcl-2), microRNA-21(miRNA-21), and low expression FAS ligand (FASLG) are reported in many cancers. Some anticancer drugs such as Levetiracetam(Lev) produce their effects via the change of expression of these biomarkers. The present study aimed to evaluate the anti-cancer effects of a new compound, Platinum Levetiracetam(Pt-Lev), gene expression of mentioned biomarkers on hepatocyte G2 (HepG2) cells compared to Lev. METHODS AND RESULTS: In this study, Human Dermal fibroblast cells (HDF) were used as the negative control group (group A) HepG2 cells were divided into three groups: untreated cancer cells as positive group (group B), groups C and D were treated with, Lev and Pt-Lev, respectively. After evaluating lethal concentration 50% (LC50) for the examined drugs using the MTT test, biomarker gene expression was evaluated by real-time PCR. No Apoptotic cell was found in groups C or D before drug treatment, but it was present using different concentrations of the drugs. Results indicated that telomerase and miRNA-21 genes expression was significantly lower and FASLG was higher in group D compared with group C but there was no significant difference for Bcl-2 expression between these two groups. CONCLUSIONS: For the first time, it was indicated that Pt-Lev has anticancer effects by inhibiting telomerase and Bcl-2 and miRNA-21 and increasing FASLG gene expression and its effects were more than Lev. It effectively exerted its anticancer effects by extending apoptosis on HepG2 cells.

The Anticancer Efficacy of Platinum Azidothymidin on Hepatocellular Carcinoma Via Affecting the Telomerase and the BcL-2 Genes Expression.

PURPOSE: The study of correlation between cancer biomarkers after treatment with anticancer drugs would represent a promising insight into the effectiveness of the drug. METHODS: In this study, after induction of hepatocellular carcinoma, rats were divided into four groups: groups A and B as healthy or control group and negative untreated cancer group respectively; groups C and D were treated with platinum azido-thymidine (0.9 mg/kg/day), a novel anti-cancer drug, and azido-thymidine (AZT) (0.3 mg/kg/day) respectively. After induction of cancer, the telomerase and Bcl-2 expression were evaluated by real-time PCR (RT-qPCR), and also Bcl-2 concentration and telomerase activity were measured by enzyme-linked immunosorbent assay (ELISA) and telomerase repeat amplification protocol (TRAP) respectively. RESULTS: A significant correlation was observed between telomerase and Bcl-2 in untreated HCC-induced rats as compared to the control group. In untreated cancer group, a direct significant correlation between telomerase activity and expression (r = 0.453, p = 0.022*) and also a negative significant correlation between telomerase activity and Bcl-2 concentration (r = - 0.43, p = 0.034*) and also between telomerase and Bcl-2 expression (r = - 0.088, p = 0.006*) was observed. In drug-treated groups, there was a significant negative correlation between telomerase expression and Bcl-2 concentration (r = - 0.45, p = 0.025) only in the AZT-treated groups. CONCLUSION: Our results indicated a correlation between cancer factors in the untreated cancerous group B and in treated groups only limited to the azithoimidin-treated group (group D). Hence, it may be possible to use this strategy to develop remarkable anticancer drugs in future studies, though this hypothesis requires more in-depth research.

Comparison between Platinum-Azidothymidine and Azidothymidine Effects on Bcl-2 and Telomerase Gene Expression in Rats with Hepatocellular Carcinoma.

BACKGROUND: High expression of telomerase and Bcl-2 are reported in hepatocellular carcinoma. Some anticancer drugs show their effects through reduction of these factors. In this study, it was aimed to investigate the effects of a new synthetic compound, platinum azidothymidine, on inhibition of telomerase and Bcl-2 expression in hepatocellular carcinoma compared to azidothymidine. METHODS: To study the effects of Pt-AZT on hepatocellular carcinoma and compare its effects with AZT in inhibition of telomerase and Bcl-2 gene expression, pathogen-free male Wistar rats (n=100) were used. They were randomly divided to 4 groups (n=25). Group A as the control group contained 25 healthy rats; in the rest of animals, preneoplastic lesions were induced in their livers (groups B, C, and D) using Solt-Farber resistant hepatocyte protocol. Cancer development was approved by a pathology laboratory. Group B was negative control (untreated), groups C and D were treated by intraperitoneal injection (IP) of Pt-AZT (0.9 mg/kg/day) and AZT (0.3 mg/kg/day), respectively for 14 days. At the end of the protocol, all rats were sacrificed and Bcl-2 and telomerase gene expression was determined using real-time PCR. RESULTS: No tumor in the livers was found in group A at any point of the study, but it was present in livers of all animals in B, C and D groups. Results showed that telomerase and Bcl-2 expression was significantly lower in group C compared with group B (0.473±0.231 vs. 5.137±5.08, p<0.001, for telomerase expression, and 0.41±0.276 vs. 7.25±11.6, p<0.001, for Bcl-2 expression) and also compared with group D (0.473±0.231 vs. 3.48±4.02, p<0.001, for telomerase expression, and 0.41±0.276 vs. 4.93±18, p<0.001, for Bcl-2 expression). CONCLUSION: For the first time, it was demonstrated that Pt-AZT has more inhibitory effect on telomerase and Bcl-2 expression than AZT. It effectively inhibits the growth of liver tumor in rats by extending apoptosis.

Effects of treatment with platinum azidothymidine and azidothymidine on telomerase activity and bcl-2 concentration in hepatocellular carcinoma- induced rats.

BACKGROUND: Telomerase activity increases in cancer cells. Bcl-2 is an antiapoptotic factor that its concentration grows in many cancer cells including hepato-cellular carcinoma cells. In this study, an attempt was made to investigate the effects of a new synthetic compound, platinum azidothymidine (Pt-AZT) on treatment of rats with Hepatocellular Carcinoma (HCC) and to compare its effects with azidothymidine (AZT) in alteration of telomerase activity and Bcl-2 concentration in HCC. METHODS: Healthy adult male Wistar rats (n = 100) were randomly divided into 4 groups (A, B, C, and D). Group A contained 25 healthy rats and was considered as the control group. Liver preneoplastic lesions were induced in remaining animals (n = 75) using Solt-Farber resistant hepatocyte protocol. These animals were randomly allocated in groups B, C and D. Group B was negative control (untreated), groups C and D were treated by intraperitoneal injection (IP) of Pt-AZT (0.9 mg/kg/day) and AZT (0.3 mg/kg/day), respectively for 14 days. After the treatment period, telomerase activity and Bcl-2 concentration were determined in the rats' liver. RESULTS: No HCC was developed in group A, but tumors were present in all other groups. Telomerase activity and Bcl-2 concentration were significantly lower in group C compared to groups B (0.159±0.06 vs. 0.577±0.116 IU/L, p < 0.001, respect-ively and 0.931±0.388 vs. 3.94±0.74 ng/ml, p < 0.001, respectively). Similar results were observed in comparison with group D (0.331±0.06 vs. 0.577±0.116 IU/L, p < 0.001, respectively and 0.931±0.388 vs. 2.94±0.594 ng/ml, respectively). There was a significant negative correlation between telomerase activity and Bcl-2 concentration only in untreated cancer group (p = 0.034). CONCLUSION: In this study, higher anticancer activity of Pt-AZT in comparison to AZT was demonstrated. It effectively inhibits the growth of liver tumor in rats through extending apoptosis.