Synergistic effects of ozone with doxorubicin on the proliferation, apoptosis and metastatic profile of luminal-B type human breast cancer cell line.

OBJECTIVE: Luminal-B type human breast cancer cell line (BT-474) to assess the synergistic effects of ozone applied after chemotherapeutic treatment with various dosages of doxorubicin, and compare the results with the effects on L929 fibroblast cell line. METHODS: Doxorubicin (1-50 M) was added to each cell lines and left to sit for 24 h at 37 °C. Then, as combination groups, half of the groups were incubated with 30 g/mL ozone for 25 min. Tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-ß), and matrix metalloproteinase-2 and - 9 (MMP-2 and MMP-9) levels were measured using the MTT test, flow cytometry, and immunocytochemistry, respectively. RESULTS: When compared to simply doxorubicin-applied cells without ozone treatment, each dose of doxorubicin + ozone treatment considerably boosted L929 viability but significantly decreased BT-474 viability. Additionally, the combination increased the apoptotic impact of doxorubicin on BT-474 but not L929 (P < 0.001). TGF-, MMP-2, and MMP-9 levels of L929 after combination were substantially higher than those of the other groups (P < 0.01). Doxorubicin's effect on BT-474's protein levels, which had significantly decreased in comparison to those of the other groups, was reversed by the combination treatment (P < 0.05). CONCLUSION: Doxorubicin's anti-proliferative and apoptotic effects were enhanced by ozone treatment in BT-474 cells, but it also repaired and healed healthy fibroblast cells that had been harmed by the cytotoxicity of the chemotherapy drug. If doxorubicin and ozone treatment are coupled, BT-474 cells may develop resistance to it through expressions of TNF-α, TGF-ß, MMP-2, and MMP-9.

Effect of aza-BODIPY-photodynamic therapy on the expression of carcinoma-associated genes and cell death mode.

BACKGROUND: Breast cancer is the most common cancer affecting women worldwide.Photodynamic therapy(PDT) has now proven to be a promising form of cancer therapy due to its targeted and low cytotoxicity to healthy cells and tissues.PDT is a technique used to create cell death localized by light after application of a light-sensitive agent.Aza-BODIPY is a promising photosensitizer for use in PDT. Our results showed that aza-BODIPY-PDT induced apoptosis, probably through p53 and caspase3 in MCF-7 cells. Future studies should delineate the molecular mechanisms underlying aza-BODIPY-PDT-induced cell death for a better understanding of the signaling pathways modulated by the therapy so that this novel technology could be implemented in the clinic for treating breast cancer. AIM: In this study,we aimed to determine the change in the expression levels of 88 carcinoma-associated genes induced by aza-BODIPY-PDT were analyzed so as to understand the specific pathways that are modulated by aza-BODIPY-PDT. MATERIAL METHOD: In this study,the molecular basis of the anti-cancer activity of aza-BODIPY-PDT was investigated.Induction of apoptosis and necrosis in MCF-7 breast cancer cells after treatment with aza- BODIPY derivative with phthalonitrile substituents (aza-BODIPY) followed by light exposure was evaluated by Annexin V 7- Aminoactinomycin D (7-AAD) flow cytometry. RESULTS: Aza-BODIPY-PDT induced cell death in MCF-7 cells treated with aza-BODIPY-PDT; flow cytometry revealed that 28 % of the cells died by apoptosis. Seven of the 88 carcinoma-associated genes that were assayed were differentially expressed -EGF, LEF1, WNT1, TCF7, and TGFBR2 were downregulated, and CASP3 and TP53 were upregulated - in cells subjected to aza-BODIPY-PDT.This made us think that the aza-BODIPY-PDT induced caspase 3 and p53-mediated apoptosis in MCF7 cells. CONCLUSION: In our study,it was determined that the application of aza-BODIPY-PDT to MCF7 cells had a negative effect on cell connectivity and cell cycle.The fact that the same effect was not observed in control cells and MCF7 cells in the dark field of aza-BODIPY indicates that aza-BODIPY has a strong phodynamic anticancer effect.

Exploring the molecular mechanism of linagliptin in osteosarcoma cell lines for anti-cancer activity.

BACKGROUND: Finding new applications for widely used current drugs is a fast and effective technique for discovering new anticancer chemicals. Osteosarcoma (OS), the most prevalent form of bone cancer, has several side effects that significantly lower patients' quality of life. This study aims to systematically examine the anti-cancer activity of linagliptin (LG) in the osteosarcoma cell line Saos-2. METHODS: MTT assays and flow cytometry were used to assess cell viability and apoptosis, respectively. qPCR array experiments were carried out to determine target gene expressions and explain the molecular mechanism of LG's action. RESULTS: Linagliptin treatment significantly decreased the viability of Saos-2 cells and hFOB1.19 cells (p < 0.001). The treatment also induced increased apoptotic effects in both Saos-2 cells (p < 0.001) and hFOB1.19 cells (p < 0.05). qPCR assays were conducted to assess cancer pathway analysis after applying specific quantities of LG to Saos-2 and hFOB1.19 cells. CONCLUSION: The findings of this study demonstrate that LG inhibits the proliferation of Saos-2 cells and induces cell death. LG supports cell death by suppressing the expression of specific genes involved in cancer pathways.

Genetic deviation associated with photodynamic therapy in HeLa cell.

Photodynamic therapy (PDT) is a method that is used in cancer treatment. The main therapeutic effect is the production of singlet oxygen (1O2). Phthalocyanines for PDT produce high singlet oxygen with absorbers of about 600-700 nm. AIM: It is aimed to analyze cancer cell pathways by flow cytometry analysis and cancer-related genes with q-PCR device by applying phthalocyanine L1ZnPC, which we use as photosensitizer in photodynamic therapy, in HELA cell line. In this study, we investigate the molecular basis of L1ZnPC's anti-cancer activity. MATERIAL METHOD: The cytotoxic effects of L1ZnPC, a phthalocyanine obtained from our previous study, in HELA cells were evaluated and it was determined that it led to a high rate of death as a result. The result of photodynamic therapy was analyzed using q-PCR. From the data received at the conclusion of this investigation, gene expression values were calculated, and expression levels were assessed using the 2-∆∆Ct method to examine the relative changes in these values. Cell death pathways were interpreted with the FLOW cytometer device. One-Way Analysis of Variance (ANOVA) and the Tukey-Kramer Multiple Comparison Test with Post-hoc Test were used for the statistical analysis. CONCLUSION: In our study, it was observed that HELA cancer cells underwent apoptosis at a rate of 80% with drug application plus photodynamic therapy by flow cytometry method. According to q-PCR results, CT values ​​of eight out of eighty-four genes were found to be significant and their association with cancer was evaluated. L1ZnPC is a new phthalocyanine used in this study and our findings should be supported by further studies. For this reason, different analyses are needed to be performed with this drug in different cancer cell lines. In conclusion, according to our results, this drug looks promising but still needs to be analyzed through new studies. It is necessary to examine in detail which signaling pathways they use and their mechanism of action. For this, additional experiments are required.

Ozone combined with doxorubicin exerts cytotoxic and anticancer effects on Luminal-A subtype human breast cancer cell line.

OBJECTIVE: We aimed to examine the potential anticancer effects of ozone applied after chemotherapeutic treatment with different concentrations of doxorubicin in Luminal-A subtype of human breast cancer cell line (MCF-7) and compare the results with effects on L929 fibroblast cell line. METHODS: Both cell lines were incubated with increasing doses of doxorubicin (1-50 µM) for 24 h at 37°C. Then, half of groups were incubated with 30 µg/mL ozone for 25 min as combination groups. Cell viability was analyzed by MTT assay, apoptosis by flow cytometry, and levels of tumor necrosis factor alpha, transforming growth factor beta, and matrix metalloproteinase-2 and MMP-9 by immunocytochemistry. RESULTS: Doxorubicin + ozone treatment enhanced viability of L929 (p<0.01) but reduced viability of MCF-7 compared to only doxorubicin-applied cells without ozone treatment (p<0.001). This combined treatment also enhanced apoptotic effect of doxorubicin on MCF-cells (p<0.001), but not on L929. It significantly increased all protein levels of L929 compared with those of other groups (p<0.05 for tumor necrosis factor alpha and MMP-2; p<0.01 for transforming growth factor beta and MMP-9). This treatment reversed the effect of doxorubicin on tumor necrosis factor alpha levels and considerably reduced MMP-2 and MMP-9 levels of MCF-7 compared with those of control group (p<0.01 and p<0.001, respectively). CONCLUSION: Ozone treatment potentiated the apoptotic and anticancer activities of doxorubicin in MCF-7 cells and showed repairing and healing effect on healthy fibroblast cells, which were damaged from cytotoxic effects of chemotherapeutic agent. MCF-7 cells may acquire sensitivity against the doxorubicin combined with ozone treatment through activating tumor necrosis factor alpha, MMP-2, and MMP-9 expressions.

Ozone combined with doxorubicin exerts cytotoxic and anticancer effects on Luminal-A subtype human breast cancer cell line

SUMMARY OBJECTIVE: We aimed to examine the potential anticancer effects of ozone applied after chemotherapeutic treatment with different concentrations of doxorubicin in Luminal-A subtype of human breast cancer cell line (MCF-7) and compare the results with effects on L929 fibroblast cell line. METHODS: Both cell lines were incubated with increasing doses of doxorubicin (1-50 μM) for 24 h at 37°C. Then, half of groups were incubated with 30 μg/mL ozone for 25 min as combination groups. Cell viability was analyzed by MTT assay, apoptosis by flow cytometry, and levels of tumor necrosis factor alpha, transforming growth factor beta, and matrix metalloproteinase-2 and MMP-9 by immunocytochemistry. RESULTS: Doxorubicin + ozone treatment enhanced viability of L929 (p<0.01) but reduced viability of MCF-7 compared to only doxorubicin-applied cells without ozone treatment (p<0.001). This combined treatment also enhanced apoptotic effect of doxorubicin on MCF-cells (p<0.001), but not on L929. It significantly increased all protein levels of L929 compared with those of other groups (p<0.05 for tumor necrosis factor alpha and MMP-2; p<0.01 for transforming growth factor beta and MMP-9). This treatment reversed the effect of doxorubicin on tumor necrosis factor alpha levels and considerably reduced MMP-2 and MMP-9 levels of MCF-7 compared with those of control group (p<0.01 and p<0.001, respectively). CONCLUSION: Ozone treatment potentiated the apoptotic and anticancer activities of doxorubicin in MCF-7 cells and showed repairing and healing effect on healthy fibroblast cells, which were damaged from cytotoxic effects of chemotherapeutic agent. MCF-7 cells may acquire sensitivity against the doxorubicin combined with ozone treatment through activating tumor necrosis factor alpha, MMP-2, and MMP-9 expressions.