Molecular targeted approaches to cancer therapy and prevention using chalcones.
There is an emerging paradigm shift in oncology that seeks to emphasize molecularly targeted approaches for cancer prevention and therapy. Chalcones (1,3-diphenyl-2-propen-1-ones), naturally-occurring compounds with widespread distribution in spices, tea, beer, fruits and vegetables, consist of open-chain flavonoids in which the two aromatic rings are joined by a three-carbon α, β-unsaturated carbonyl system. Due to their structural diversity, relative ease of chemical manipulation and reaction of α, β-unsaturated carbonyl moiety with cysteine residues in proteins, some lead chalcones from both natural products and synthesis have been identified in a variety of screening assays for modulating important pathways or molecular targets in cancers. These pathways and targets that are affected by chalcones include MDM2/p53, tubulin, proteasome, NF-kappa B, TRIAL/death receptors and mitochondria mediated apoptotic pathways, cell cycle, STAT3, AP-1, NRF2, AR, ER, PPAR-γ and β-catenin/Wnt. Compared to current cancer targeted therapeutic drugs, chalcones have the advantages of being inexpensive, easily available and less toxic; the ease of synthesis of chalcones from substituted benzaldehydes and acetophenones also makes them an attractive drug scaffold. Therefore, this review is focused on molecular targets of chalcones and their potential implications in cancer prevention and therapy.
Danielle D
DD
Jandial
Christopher A
CA
Blair
Saiyang
S
Zhang
Lauren S
LS
Krill
Yan-Bing
YB
Zhang
Department of Urology, University of California, Irvine, 101 The City Drive South, Rt.81 Bldg.55 Rm.302, Orange CA 92868, USA. xzi@uci.edu.
Xiaolin
X
Zi
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D047188:Chalcones / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008517:Phytotherapy; D010946:Plants, Medicinal; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
D000972:Antineoplastic Agents, Phytogenic; D047188:Chalcones