Abstract
Cancer patients frequently use complementary medicine. Curcumin (CUR) and its derivates (from the extract of Curcuma longa L.) represent some of the most frequently used ones, having a long history in traditional Asian medicine. CUR was demonstrated, both in vitro and in vivo, to have significant anti-inflammatory effects, thus potentially counteracting cancer-promoting inflammation, which is a hallmark of cancer. CUR modulate a plethora of signaling pathways in cancer cells, comprising the NF-κB (nuclear factor k-light-chain-enhancer of activated B cells), the JAK/STAT (Janus-Kinase/Signal Transducers and Activators of Transcription), and the TGF-β (transforming growth factor-β) pathways. Furthermore, CUR confers properties of electron receptors, which destabilize radical oxygen species (ROS), explaining its antioxidant and anti-apopototic effects. Although CUR has a low bioavailability, its role in advanced cancer treatment and supportive care was addressed in numerous clinical trials. After promising results in phase I–II trials, multiple phase III trials in different indications are currently under way to test for direct anti-cancer effects. In addition, CUR exerts beneficial effects on cancer treatment-related neurotoxcity, cardiotoxicity, nephrotoxicity, hemato-toxicity, and others. More efficient galenic formulations are tested to optimze CUR’s usability in cancer treatment. This review should provide a comprehensive overview of basic science, and pre-clinical and clinical data on CUR in the field of oncology.
Highlights
Cancer patients frequently use natural and herbal products during cancer treatment
A recent Italian review reported that half of all cancer patients use complementary and/or alternative medical (CAM) approaches [1]; the choice of CAM varies widely and may depend on the cultural setting and availability of interventions and drugs
Numerous natural products or substances derived from plants or other life forms were evaluated in different medical conditions, especially in cancer
Summary
Cancer patients frequently use natural and herbal products during cancer treatment. A recent Italian review reported that half of all cancer patients use complementary and/or alternative medical (CAM) approaches [1]; the choice of CAM varies widely and may depend on the cultural setting and availability of interventions and drugs. Pignanelli et al [20] synthesized CUR analogs capable of efficiently killing triple-negative, inflammatory breast, p53-negative colorectal, and different blood cancer cell lines, by manipulating and increasing ROS species in these cells, which translates to the induction of apoptosis These analogs proved to be more toxic and effective than natural CUR, with lower intracellular concentrations achieving the same effects. Antitumor effects were increased when both cisplatinum and CUR were combined and administered in increasing dosages, achieving significantly higher cell death and tumor regression rates compared to their application as monotherapy Another possible synergistic interaction is with anti-EGFR therapy, targeting the EGFR/MAPK (mitogen-activated protein kinase) pathway known to stimulate cell proliferation [41]. Downregulation of the HGF/MET pathway Downregulation of stemness markers (i.e., CD133, CD44)
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