ABSTRACT
Introduction: Telomere maintenance is essential for the continued proliferation of dividing cells, and is implicated in chromosome stability and cell immortalization. Telomerase activity, that allows cancer cells to maintain their telomeric DNA for an indefinite replicative capacity, is an attractive target against cancer. A well known benzylisoquinoline alkaloid, papaverine, we focused on to evaluate its antiproliferaive effects on breast cancer MCF7 cells
Methods: Cytotoxicity of the commercially available pure compound papaverine HCl [Sigma] was determined by MTT assay. A modified quantitative real-time polymerase chain reaction [PCR]-based telomerase repeat amplification protocol [TRAP] was used to estimate relative telomerase activity in papaverine-treated cells in comparison with the untreated control cells. Relative expression level of the catalytic subunit of telomerase [hTERT] gene was estimated using real time reverse transcription-PCR [RT-PCR]
Results: IC50 concentration of papaverine after 48 hours treatment was measured to 120 micromolar. At this concentration telomerase activity showed a considerable decrease [almost 70% in comparison with untreated control cells], in a concentration dependent manner. Quantitative real-time RT-PCR experiments indicated a similar reduction in transcription level of hTERT gene under treatment with papaverine
Conclusion: Papaverine is a potent natural compound in suppression of cancer cell immortality most probably by anti-telomerase activity. It is a valuable putative compound for further development of promising anti-cancer agents
ABSTRACT
Crocin is a major constituent of saffron, the dried stigmas of Crocus sativus L., which is used mainly as a herbal medicine or a food coloring agent around the world. Novel publications reporting a cancer preventive effect for crocin motivated us to evaluate telomerase activity, the main cause of immortality in cancer cells, under treatment with crocin. IC50 concentration of crocin was estimated in MCF-7 cell line, a breast adenocarcinoma cancer model, by MTT [3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide] test after 48 hours of treatment. A conventional telomere repeat amplification protocol [TRAP] assay and a real-time quantitative telomere repeat amplification protocol [qTRAP] assay were used to estimate relative telomerase activity in crocin-treated cells in comparison with untreated control cells. Telomerase activity in the treated cells with different concentrations of crocin up to IC50 showed an increment after administration of very low doses of crocin, whereas higher concentrations of crocin remarkably inhibited the enzyme in a dose-dependent manner. IC50 values of crocin reduced by 85% in comparison with untreated control cells. qTRAP estimations show a good correlation with the conventional assay results. Antiproliferative effect of crocin in cancer cells is probably due to strong inhibition of telomerase activity
ABSTRACT
Recent studies indicate the potential role of bee venom [BV] in cancer therapy. Moreover, many evidences suggest that the regulation of apoptosis plays an important role in tumorigenesis. Considering the apoptosis-inducing and anti-tumor effect of BV, this study aimed to determine the type of the cell death induced by BV on MOLT-4 cancer cell line. In this experimental study, MOLT-4 cells were first cultured in RPMI-1640 medium in plate, then the cells were treated with different concentrations [1, 3, 6 and 8 microg/ml] of BV for 24 and 48 h. Morphology of cells, cell viability and type of the cell death were induced by BV were evaluated using inverted microscopy, the MTT assay and flow cytometry, respectively. Cell survival findings showed the BV CC[50] values of 6.3 and 0.6 microg/ ml for the cell line in 24 and 48 h, respectively. Moreover, Morphological and Annexin-V antibody analyses indicated that the BV-induced cell death might be an apoptosis. As BV can induce the apoptosis in MOLT-4 cancer cells. Thus, it would bring hope for designing novel drugs for cancer-therapy in future
ABSTRACT
Differentiation therapy is one of the methods for treatment of cancer. In this method, some drugs such as All-trans Retinoic Acid, are used which can inhibit proliferation of cancerous cells and induce cell differentiation. Previus experiments showed some anti-proliferation materials, anti-inflammation materials or anti-oxidant materials could influence the effects of such drugs and decrease resulting side effects. In this research the effects of the Honey Bee Venom, on All-trans Retinoic Acid functions was measured. In this experimental project we used HL-60 cell line belonging to acute promyelocyte leukemia. The HL-60 cell line was obtained from Pasteur Institute of Iran, and were grown in RPMI 1640 medium [Roswell Park Memorial Institute] containing 10% FBS [Fetal Bovine Serum] and 1% streptomycin-penicilin. We used MTT [3-[4, 5-Dimethylthiazol-2-yl]-2, 5-Diphenyltetrazolium bromide] and NBT [Nitro-Blue tetrazolium chloride] tests for these purposes. All experiments were done three times and data were analyzed using SPSS. Both Honey Bee Venom and All-trans Retinoic Acid could inhibit proliferation of HL-60 cells, also All-trans Retinoic Acid could induce differentiation in this cells. The amount of differentiation was increased significantly [p<0.01] in the presence of Honey Bee Venom. On the base of our findings, it seemed that Honey Bee Venom could increase anti cancer effects of All-trans Retinoic Acid