Abstract
Despite considerable improvements in the tolerance and efficacy of novel chemotherapeutic agents, the mortality of hematological malignancies is still high due to therapy relapse, which is associated with bad prognosis. Dietary polyphenolic compounds are of growing interest as an alternative approach, especially in cancer treatment, as they have been proven to be safe and display strong antioxidant properties. Here, we provide evidence that both resveratrol and curcumin possess huge potential for application as both chemopreventive agents and anticancer drugs and might represent promising candidates for future treatment of leukemia. Both polyphenols are currently being tested in clinical trials. We describe the underlying mechanisms, but also focus on possible limitations and how they might be overcome in future clinical use – either by chemically synthesized derivatives or special formulations that improve bioavailability and pharmacokinetics.
Highlights
With more than 3 million new cases and 1.7 million deaths each year, cancer is the most important cause of death and morbidity in Europe after cardiovascular diseases
In contrast to HL-60 cells that are killed via the CD95-CD95 ligand pathway [105,106], resveratrol has been reported to drive apoptosis in CD95-signaling-resistant acute lymphoblastic leukemia (ALL) cell lines by activating the intrinsic apoptotic pathway whereas normal peripheral blood mononuclear cells (PBMCs) are not affected [107]
By genome-wide microarray analysis performed under the same conditions we demonstrated that especially cell cycle genes and genes from the JAK/signal transducers and transcriptional activators (STATs) signaling pathway were downregulated whereas heat shock proteins are among the 10 most upregulated genes [193]
Summary
With more than 3 million new cases and 1.7 million deaths each year, cancer is the most important cause of death and morbidity in Europe after cardiovascular diseases. The. Molecules 2010, 15 most recent cancer statistics resource, GLOBOCAN 2008, counted 47,500 new cases of leukemia and more than 32,000 deaths in European men. Thereby, leukemia reached seventh place on the list of the ten most frequent cancer types in men. Leukemia develops from hematopoietic stem cells that escape the normal control mechanisms thereby interrupting their capacity to differentiate in mature blood cells [1,2,3]. As a result of uncontrolled proliferation of hematological progenitor cells, excessive number of malignant cells accumulates in the bone marrow where they replace normal marrow tissue and affect physiological production of blood cells. We highlight the role of their pro-oxidant effects and present an overview about the efforts that were undertaken in order to improve bioavailability and pharmacokinetics of resveratrol and curcumin
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