Ankaferd Blood Stopper (ABS), a unique traditional herbal mixture, has been used topically to stop bleeding for centuries in Anatolia. As well as ABS has been used as a blood-stopping agent, it may also have a considerable therapeutic benefit, because of its anti-infective, anti-neoplastic, and wound healing properties. The aim of this study is to investigate the anti-neoplastic effects of the ABS on myeloma cell line, in vitro and on the plasmocytoma development in Balb/c mice by intraperitoneal injection of pristane, in vivo. We therefore sought to evaluate the efficacy of ABS on MM cells and to study the modulation of cell-death pathways. The cytotoxicity of ABS against the MM cell lines (RPMI-8226, and ARH-77) was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-dye reduction assay. Responses to ABS by RPMI-8226 and ARH-77 cell lines were dose dependent but not time dependent. The IC50 values for RPMI 8226 and ARH 77 myeloma cell lines in 24h were 12,84 μL/mL and 13,86 μL/mL, respectively. Various cell-death characteristics such as caspase-3, Bcl-2, Bax were studied in response to ABS, but we couldn’t demonstrate specific features of apoptotic cell death, in vitro. We have also investigated the effect of the ABS on the pristane (2.6.10.14-tetramethylpentadecane)-induced plasmacytoma (PCT) development on six-week-old BALB/c mice. Three groups of mice were treated with intraperitoneal ABS (1 mg/kg, 0.5mg/kg, and 0,1mg/kg) per-week for eight weeks after pristane-induced PCT development. The study was stopped at twelfth week, the remaining mice were autopsied, and peritoneal tissues were examined histologically for PCTs. A database of different groups’ mice was analyzed using Kaplan-Meier and Cox regression statistics based on variables. Kaplan-Meier analysis revealed a difference of the survival of pristane-induced alone between the groups of pristane-induced plus ABS 1 mg/kg, 0.5mg/kg, and 0.1mg/kg. (Log-rank, p=0.016; p<0.001 and p<0.001; respectively). The present results indicate that direct anti-tumor effect of ABS on pristane-induced PCT and significantly increased survival. This hypothesis needs to now be further investigated in clinical trials. Disclosures No relevant conflicts of interest to declare.
Background:The majority of Achillea species are the most important native economic plants of Anatolia. They include highly bioactive compounds, so they have therapeutic applications.Objective:In the present study, the aim was to investigate in vitro anti-oxidant, cytotoxic and pro-apoptotic effects of Achillea teretifolia Willd extracts (Turkish name: Beyaz civanperÇemi).Materials and Methods:The anti-oxidant potential of the extracts was analyzed by the free radical 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and total phenolic content methods. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to detect cytotoxicity of the extracts onhuman prostate cancer cell lines (DU145 and PC-3) and human gingival fibroblast (HGF) cells. mRNA expression levels of pro-apoptotic (bax, caspase-3) and anti-apoptotic (bcl-2) genes were measured by quantitative real-time polymerase chain reaction.Results:The results showed that extracts exhibited a remarkable DPPH scavenging activity, and total phenolic content of the methanol extract was higher than that of the water extract. As time and concentration were increased, the methanol extract exhibited a more powerful cytotoxic effect on prostate cancer cells. In prostate cancer cells, the levels of mRNA expression of the bax and caspase-3 genes were significantly up-regulated (P < 0.05), whereas the expression of bcl-2 was down-regulated (P < 0.05). In HGF cells, there were no cytotoxic effect and apoptosis induction triggered by the extracts.Conclusion:The methanol extract had more powerful anti-oxidant, cytotoxic and pro-apoptotic effects than the water extract. The extracts could be good anti-oxidant sources, and they might include anti-cancer compounds triggering the cytotoxicity and the apoptosis on prostate cancer cells.
Calcitriol and doxorubicin co-loaded liposomes created improved cytotoxicity on Namalwa cells compared to doxorubicin loaded liposomes or free drug treatments.
The most important problem in the treatment of Multiple Myeloma (MM) is the multi drug resistance (MDR) observed before and after the treatment. For this reason in MM cases an early resistance to treatment can be developed or the disease can relapsed in early period. Yet, there has been no improved drug resistance against proteazom inhibitor Bortezomib (Bor), which is used alone or with other chemotherapeutic agents in resistant or relapsed MM cases. In this study, bortezomib resistant human MM cell lines; RPMI-8226, secreting lambda light chain, and ARH-77, secreting IgG, were developed and responsible resistance mechanisms were investigated. For this purpose, by exposing to the cells to sequentially gradual doses of Bor in vitro conditions, resistant cell lines were acquired throughout one year. The IC50 values for Bor were determined after 48 hour incubation by MTT cytotoxicity assay (IC50:1,16nM for RPMI-8226 and IC80:0,6nM for ARH-77) against wild type cells. Throughout one year some cell lines resistant to 1,3nM Bor were acquired by performing Bor to both cell lines in gradual doses. In resistant cell lines IC50:18,07 for RPMI-8226 and IC50:97,56 nM for ARH-77 were determined by MTT assay. In parallel of the gradual increase in drug concentration; the expression changes of the genes of ATP binding cassette protein; MDR1 (Multi Drug Resistance Protein), MRP1 (Multi Drug Resistance Associated Protein), BCRP (Breast Cancer Resistance Protein); and LRP (Lung Resistant Protein) which is responsible for accumulation of the drug in cytoplasm with the aid of nuclear membrane were determined with Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) and densitometric analysis. In resistant cells, high expression of MDR1, MRP1, BRCP and LRP genes showed that; pumping the drug out of the cell membrane and decrease in accumulation of the drug in the cytoplasm had effects on the resistant mechanisms against Bor. Furthermore, expression changes of an important sing of apoptosis ‘caspase-3’, pro-apoptotic ‘bax’ and an anti-apoptotic ‘bcl-2’ genes were examined by RT-PCR and we could come to a point that when compared the sensitive cells to resistant cells, expression of caspase-3 gene and pro-apoptotic bax protein decreased but bcl-2 gene expression increased in resistant cell lines. Finally, we concluded that resistant cell lines acquired resistance against apoptosis by means of mitochondria. By means of this project, the genes which are responsible for secondary drug resistance in ARH-77 and RPMI-8226 MM cell lines in vitro conditions against Bor were determined. Also resistance mechanisms against apoptosis were demonstrated. Cross resistance to different chemotherapeutic agents mechanisms are still continuing.
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