ABSTRACT
Background & objectives: Several studies have provided evidence that opioids may play a role in cancer recurrence and metastasis. Multiple research data indicate that morphine can act as a proliferative or suppressive agent on tumour cells depending on the applied concentration. Therefore, this study was aimed to investigate whether the presence of clinically relevant concentrations of morphine has any effect on the efficacy of paclitaxel, a widely used chemotherapeutic drug, on the viability and apoptosis of human triple-negative breast cancer cell line. Methods: MDA.MB.231 cells were treated with paclitaxel in the presence or absence of morphine and examined for cell proliferation by the MTT assay. In addition, the effect of morphine on paclitaxel- induced apoptosis was investigated by flow cytometric assay and by the ratio of Bax/Bcl-2 mRNA expression levels with quantitative real-time (qRT)-PCR. Results: Morphine significantly increased the proliferation of breast cancer cells at low concentrations (0.1-2.5 ?M) but higher concentrations showed cytotoxic effect. Pre-treatment with 0.1 or 1 ?M of morphine decreased the paclitaxel-induced cytotoxicity, the proportion of apoptotic cell, and the ratio of Bax/Bcl-2 mRNA expressions. Interpretation & conclusions: Our data suggest that morphine promotes breast cancer cell viability at clinically relevant plasma concentrations and reduces the apoptotic effect of paclitaxel. This interaction may be very important in clinical settings; however, more studies are needed to explore the plausible mechanisms of interaction and to correlate such findings through in vivo animal studies as well as clinically.
ABSTRACT
The aim of our study is to examine the effect of extracellular ATP whether it is correlated with intracellular Ca concentrations ([Ca2+]i) on human liver hepatocellular cells (HepG2). The extracellular ATP is responsible for regulating both cells signaling and cell functions. ATP maintains these effects through purinergic P2 receptors. The extracellular ATP promotes the release of Ca2+ from the Ca2+ stores to the cytoplasm in the cell and increases [Ca2+] I in the cell. In our study, various concentrations of ATP (10-3M-10-7M) were applied to HepG2 cells and incubated for 24 hours, 48 hours, and 72 hours. At these concentrations, the proliferation of cells and apoptosis of the cells was examined for 24 hours, 48 hours, and 72 hours. Similarly, cells with different ATP concentrations incubated for 24 hours and 48 hours were loaded with Indo 1FF AM calcium indicator to measure [Ca2+]i. Surprising results were obtained, 10-6M-10-7M extracellular ATP was found to be more toxic than 10-3 M-10-4 M extracellular ATP, (p<0.05). Low concentrations of ATP also reduced [Ca2+]i for 24 hours and 48 hours of incubations (p<0.01). As a result, low concentration extracellular ATP is more toxic in HepG2 cells. At the same time, the extracellular ATP correlates with [Ca2+]i.