Curcumin synergizes with resveratrol to inhibit colon cancer.
Development and progression of many malignancies, including colorectal cancer, are associated with activation of multiple signaling pathways. Therefore, inhibition of these signaling pathways with noncytotoxic natural products represents a logical preventive and/or therapeutic approach for colon cancer. Curcumin and resveratrol, both of which inhibit the growth of transformed cells and colon carcinogenesis, were selected to examine whether combining them would be an effective preventive and/or therapeutic strategy for colon cancer. Indeed, the combination of curcumin and resveratrol was found to be more effective in inhibiting growth of p53-positive (wt) and p53-negative colon cancer HCT-116 cells in vitro and in vivo in SCID xenografts of colon cancer HCT-116 (wt) cells than either agent alone. Analysis by Calcusyn software showed synergism between curcumin and resveratrol. The inhibition of tumors in response to curcumin and/or resveratrol was associated with the reduction in proliferation and stimulation of apoptosis accompanied by attenuation of NF-kappaB activity. In vitro studies have further demonstrated that the combinatorial treatment caused a greater inhibition of constitutive activation of EGFR and its family members as well as IGF-1R. Our current data suggest that the combination of curcumin and resveratrol could be an effective preventive/therapeutic strategy for colon cancer.
John D. Dingell VA Medical Center, 4646 John R, Room B-4238, Detroit, MI 48201, USA. a.majumdar@wayne.edu
Adhip P N
AP
Majumdar
Sanjeev
S
Banerjee
Jyoti
J
Nautiyal
Bhaumik B
BB
Patel
Vaishali
V
Patel
Jianhua
J
Du
Yingjie
Y
Yu
Althea A
AA
Elliott
Edi
E
Levi
Fazlul H
FH
Sarkar
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D003474:Curcumin / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017978:Receptors, Growth Factor / Q000378:metabolism; D000077185:Resveratrol; D012984:Software; D013267:Stilbenes / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D009687:Nuclear Proteins; D017978:Receptors, Growth Factor; D013267:Stilbenes; D016159:Tumor Suppressor Protein p53; D003474:Curcumin; D000077185:Resveratrol