Opioid-regulated pro- and anti-apoptotic gene expression in cancer cells

Morphine, as well as opioid peptides, are well-known powerful analgesics. In addition to their use in the treatment of pain, opioids appear to be important in the growth regulation of neoplastic tissue. However, little is known on the influence of opioid peptides on apoptosis modulation in cancer cells. In the present study, we evaluated the effect of the µ-opioid receptor (MOR)-selective peptide, morphiceptin and its two synthetic analogs, on mRNA expression and protein levels of some crucial factors involved in apoptosis in three human cancer cell lines: MCF-7, HT-29, and SH-SY5Y. Using real-time PCR and ELISA assays, we have shown that the selected opioid peptides enhanced apoptosis of cancer cells by increasing the expression of pro-apoptoticc Bax and caspase-3, and decreasing expression of anti-apoptotic Bcl-2. Additionally, flow cytometry analysis performed on MCF-7 cells treated with annexin V/propidium iodide confirmed that the tested opioid peptides induced apoptosis in cancer cells. However, induction of apoptosis was not reversed by the opioid antagonist, naloxone, which suggests that this process is not mediated by the opioid receptors.