From chemoprevention to chemotherapy: common targets and common goals.
Three decades of research have revealed that cancer is easier to prevent than to treat and that consumption of certain fruits and vegetables can reduce the risk of cancer. Whereas chemotherapy is designed to destroy cancer after it appears, chemoprevention involves the abrogation or delay in the onset of cancer. Regardless of whether a chemopreventive or chemotherapeutic approach is taken, cancer is a multifactorial disease that requires modulation of multiple pathways and multiple targets. Various molecular targets of chemoprevention are also relevant to the therapy of cancer. These targets include the activation of apoptosis; suppression of growth factor expression or signalling; downregulation of antiapoptotic proteins; suppression of phosphatidylinositol-3'-kinase/Akt, NF-kappaB, Janus kinase-signal transducer and activator of transcription and activator protein-1 signalling pathways; and downregulation of angiogenesis through inhibition of vascular endothelial growth factor expression, cyclooxygenase-2, matrix metalloproteinase-9, urokinase-type plasminogen activator, adhesion molecules and cyclin D1. Pharmacologically safe phytochemicals that have been identified from plants or their variant forms can modulate these molecular targets. These phytochemicals include genistein, resveratrol, dially sulfide, S-ally cysteine, allicin, lycopene, capsaicin, curcumin, 6-gingerol, ellagic acid, ursolic acid, betulinic acid, flavopiridol, silymarin, anethol, catechins and eugenol. Recent work has shown that these phytochemicals also can reverse chemoresistance and radioresistance. Because of their pharmacological safety, these agents can be used alone to prevent cancer and in combination with chemotherapy to treat cancer.
The University of Texas M.D. Anderson Cancer Center, Cytokine Research Section, Department of Experimental Therapeutics, PO Box 143, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. aggarwal@mdanderson.org
Bharat B
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Aggarwal
Yasunari
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Takada
Oommen V
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Oommen
D018890:Chemoprevention / Q000639:trends*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015536:Down-Regulation; D018432:Drug Resistance, Multiple; D004358:Drug Therapy / Q000639:trends; D006133:Growth Substances / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D004364:Pharmaceutical Preparations; D050791:STAT Transcription Factors / Q000037:antagonists & inhibitors; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors
D006133:Growth Substances; D016328:NF-kappa B; D004364:Pharmaceutical Preparations; D050791:STAT Transcription Factors; D018808:Transcription Factor AP-1; D051546:Cyclooxygenase 2