With no discernable toxicity, curcumin has been shown to inhibit the development of transformed cells and colon carcinogenesis at the initiation, promotion and progression stages in carcinogen induced rodent models. Development of azoxymethane induced preneoplastic and neoplastic lesions of the colon is also inhibited in experimental animals fed a diet plan containing 1. 6% curcumin. In addition, curcumin has been reported to avoid adenoma development in the intestinal tract of Min / mice, a model of human familial adenomatous polyposis 25.
In a Phase I clinical trial, curcumin was shown to be efficient in inhibiting tumor Cryptotanshinone development 26. We reported that curcumin in combination with ERRP, a pan erbB inhibitor leads to a better inhibition of the growth of colon cancer cells that either agent alone 28. We have also reported that curcumin acts synergistically with FOLFOX in inhibiting development of colon cancer cells in vitro. These and other related observations have prompted us to undertake the current investigation. Our doing work hypothesis, for that reason, is that a blend of dasatinib and curcumin will be an effective therapeutic method for colorectal neoplasia and/or cancer. We even more hypothesize that this improved effectiveness is the end result of an attenuation of a number of signaling pathways leading to inhibition of transformation properties of colon cancer cells.
Human colon cancer HCT 116 p53 wild PH-797804 variety, HT 29, and HCT 116 p53 null and SW 620 cells have been utilized to investigate efficacy of mixed treatment of dasatinib in and curcumin in growth inhibition. HCT 116, HT 29 and SW 620 cells were obtained from American Variety Culture Collection, whereas HCT 116 p53 null cells, originally generated in Dr. Bert Vogelstein laboratory at John Hopkins University, Baltimore, MD, have been obtained from Dr Ping Dou at Karmanos Cancer Institute. The cells were maintained in tissue culture flasks in Dulbeccos modified Eagle medium in a humidified incubator at 37 C in an atmosphere of 95% air and 5% CO2. The cell culture medium was supplemented with 5% FBS and 1% antibiotic/ antimycotic. Human umbilical vein endothelial cells, a kind present from Dr.
Fazlul Sarkar at the Karmanos Cancer Institute, Detroit, MI, have been utilised for angiogenesis assay. Endothelial growth medium with nutrient supplements have been bought from Lonza Walkersville Inc.. Furthermore, c-Met Inhibitors the cell culture medium was supplemented with 5% FBS and 1% antibiotic/antimycotic. Medium was modified three times a week and cells were passaged employing trypsin/EDTA. Dulbeccos modified Eagle medium, fetal bovine serum, and antibiotic/ antimycotic have been obtained from GIBCO BRL. Dasatinib was purchased from LC laboratories. Protease inhibitor cocktail, 3 2,5 diphenyltetrazolium bromide, and all other chemicals had been obtained from Sigma. Anti p EGFRs, p HER2, p HER3, p Src, Src, p Akt, p Erk, BclXL and Cox 2 p IGF 1R, IGF 1, IGFBP3 and Rb were bought from Cell Signaling. Antibodies to B actin antibody was obtained from Sigma.
Chemiluminescence detection of proteins was carried out with the use of a kit from Amersham Biosciences/Amersham Pharmacia Biotech.
In a Phase I clinical trial, curcumin was shown to be efficient in inhibiting tumor Cryptotanshinone development 26. We reported that curcumin in combination with ERRP, a pan erbB inhibitor leads to a better inhibition of the growth of colon cancer cells that either agent alone 28. We have also reported that curcumin acts synergistically with FOLFOX in inhibiting development of colon cancer cells in vitro. These and other related observations have prompted us to undertake the current investigation. Our doing work hypothesis, for that reason, is that a blend of dasatinib and curcumin will be an effective therapeutic method for colorectal neoplasia and/or cancer. We even more hypothesize that this improved effectiveness is the end result of an attenuation of a number of signaling pathways leading to inhibition of transformation properties of colon cancer cells.
Human colon cancer HCT 116 p53 wild PH-797804 variety, HT 29, and HCT 116 p53 null and SW 620 cells have been utilized to investigate efficacy of mixed treatment of dasatinib in and curcumin in growth inhibition. HCT 116, HT 29 and SW 620 cells were obtained from American Variety Culture Collection, whereas HCT 116 p53 null cells, originally generated in Dr. Bert Vogelstein laboratory at John Hopkins University, Baltimore, MD, have been obtained from Dr Ping Dou at Karmanos Cancer Institute. The cells were maintained in tissue culture flasks in Dulbeccos modified Eagle medium in a humidified incubator at 37 C in an atmosphere of 95% air and 5% CO2. The cell culture medium was supplemented with 5% FBS and 1% antibiotic/ antimycotic. Human umbilical vein endothelial cells, a kind present from Dr.
Fazlul Sarkar at the Karmanos Cancer Institute, Detroit, MI, have been utilised for angiogenesis assay. Endothelial growth medium with nutrient supplements have been bought from Lonza Walkersville Inc.. Furthermore, c-Met Inhibitors the cell culture medium was supplemented with 5% FBS and 1% antibiotic/antimycotic. Medium was modified three times a week and cells were passaged employing trypsin/EDTA. Dulbeccos modified Eagle medium, fetal bovine serum, and antibiotic/ antimycotic have been obtained from GIBCO BRL. Dasatinib was purchased from LC laboratories. Protease inhibitor cocktail, 3 2,5 diphenyltetrazolium bromide, and all other chemicals had been obtained from Sigma. Anti p EGFRs, p HER2, p HER3, p Src, Src, p Akt, p Erk, BclXL and Cox 2 p IGF 1R, IGF 1, IGFBP3 and Rb were bought from Cell Signaling. Antibodies to B actin antibody was obtained from Sigma.
Chemiluminescence detection of proteins was carried out with the use of a kit from Amersham Biosciences/Amersham Pharmacia Biotech.
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