Morphine is considered the “gold standard” for relieving pain and is currently one of the most effective drugs available clinically for the management of severe pain associated with cancer. In addition to its use in the treatment of pain, morphine appears to be important in the regulation of neoplastic tissue. Although morphine acts directly on the central nervous system to relieve pain, its activities on peripheral tissues are responsible for many of the secondary complications. Therefore, understanding the impact, other than pain control, of morphine on cancer treatment is extremely important. The effect of morphine on tumor growth is still contradictory, as both growth-promoting and growth-inhibiting effects have been observed. Accumulating evidence suggests that morphine can affect proliferation and migration of tumor cells as well as angiogenesis. Various signaling pathways have been suggested to be involved in these extra-analgesic effects of morphine. Suppression of immune system by morphine is an additional complication. This review provides an update on the influence of morphine on the growth and migration potential of tumor cells.

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Sesquiterpene lactones (SLs) are plant-derived compounds that are abundant in plants of the Asteraceae family and posses a broad spectrum of biological activities, ranging from anti-inflammatory, phytotoxic, antibacterial, and antifungal to cytotoxic/anticancer. In recent years, anticancer properties of these compounds and molecular mechanisms of their action have been studied extensively on numerous cell lines and also on experimental animals. SLs have been shown to disrupt cellular redox balance and induce oxidative stress in cancer cells. Oxidative stress is associated with increased production of reactive oxygen species (ROS) which in turn can promote many aspects of cancer development and progression. On the other hand, ROS, which initiate apoptosis via the mitochondrial-dependent pathway, can also be used to kill cancer cells, if they can be generated in cancer. One of the most important regulators of the redox equilibrium in the cells is reduced glutathione (GSH). In cancer cells, GSH levels are higher than in normal cells. Therefore, SL can induce apoptosis of cancer cells by decreasing intracellular GSH levels. The use of SL which can affect intracellular redox signaling pathways can be considered an interesting approach for cancer treatment. In this review, we give a brief description of the mechanisms and pathways involved in oxidative stress-induced anticancer activity of SL.

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Opioid receptors and opioid peptides constitute the endogenous opioid system. The most relevant function of the opioid system seems to be the inhibitory modulation of nociceptive information at supraspinal, spinal and peripheral sites, although it is also implicated in the modulation of many other processes in the body. Centrally acting plant opiates, such as morphine, are the most frequently used analgesics for the relief of severe pain, even though their undesired side-effects are serious limitation to their usefulness. Opioid peptides have the potential to be pharmaceutical agents for the treatment of pain, devoid of side-effects accompanying morphine. Unfortunately, peptides are generally hydrophilic compounds that will not enter the central nervous system via passive diffusion, due to the existence of the blood-brain barrier. Peptides are also easily degraded by proteolytic enzymes which further reduces their therapeutic value. Therefore, the design of peptide analogs based on the sequence of endogenous opioid peptides must be focused on increasing bioavailability and enhancing brain uptake.