Parisa Ziasarabi1, Amirhossein Sahebkar2,3,4, Faezeh Ghasemi5. 1. Laboratorio de Psicobiología, Campus Santiago Ramón y Cajal, University of Sevilla, Sevilla, Spain. 2. Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. sahebkara@mums.ac.ir. 3. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. sahebkara@mums.ac.ir. 4. School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. sahebkara@mums.ac.ir. 5. Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran. Ghasemi_808@yahoo.com.
Abstract
INTRODUCTION: Breast cancer is one of the main challenging areas in cancer treatment. Natural compounds such as curcumin and berberine have been approved with anticancer effects and are more favorable to people. Here, we investigated the potential synergistic anticancer effects of these two compounds in combination with the standard cancer drug 5-FU on the growth of MCF-7 breast cancer cells. MATERIALS AND METHODS: This study tested the effects of six different treatments on cancer cell growth: A) control; B) curcumin; C) berberine; D) 5-FU; E) curcumin + berberine; and F) curcumin + berberine + 5-FU. The IC50 concentration of each treatment on cancer cell growth was determined using the MTT assay. Invasiveness of cells grown in 3D culture was analyzed using the transwell chamber technique. Expression levels of genes involved in cancer cell growth and survival (WNT1, APC, AXIN1, CTNNB1, TCF, MTOR, AKT1, MAPK1, PTEN, BIRC5, CCNG1) were evaluated by real-time PCR. RESULTS: There was a reduction in cancer cell growth and invasion, and an increase in cellular decomposition across all treatment groups compared to the control with the strongest effects seen in the combined curcumin/berberine/5-FU group. The expression levels of all tested genes were altered in all treatment groups compared to the control, with that of WNT1, CTNNB1, TCF, MTOR, AKT1, BIRC5, and CCND1 showing the most robust changes in the combined curcumin/berberine/5-FU treatment. CONCLUSIONS: All treatment groups had anti-growth, anti-invasion, and pro-apoptotic effects on MCF-7 breast cancer cells in culture. In addition, all treatment groups showed changes in the expression of the genes involved in cancer cell growth and survival with the strongest effects found for the curcumin/berberine/5-FU combination. Therefore, curcumin and berberine may improve the anticancer effects of chemotherapy and these natural compounds should undergo further testing as potential adjuvants.
INTRODUCTION: Breast cancer is one of the main challenging areas in cancer treatment. Natural compounds such as curcumin and berberine have been approved with anticancer effects and are more favorable to people. Here, we investigated the potential synergistic anticancer effects of these two compounds in combination with the standard cancer drug 5-FU on the growth of MCF-7 breast cancer cells. MATERIALS AND METHODS: This study tested the effects of six different treatments on cancer cell growth: A) control; B) curcumin; C) berberine; D) 5-FU; E) curcumin + berberine; and F) curcumin + berberine + 5-FU. The IC50 concentration of each treatment on cancer cell growth was determined using the MTT assay. Invasiveness of cells grown in 3D culture was analyzed using the transwell chamber technique. Expression levels of genes involved in cancer cell growth and survival (WNT1, APC, AXIN1, CTNNB1, TCF, MTOR, AKT1, MAPK1, PTEN, BIRC5, CCNG1) were evaluated by real-time PCR. RESULTS: There was a reduction in cancer cell growth and invasion, and an increase in cellular decomposition across all treatment groups compared to the control with the strongest effects seen in the combined curcumin/berberine/5-FU group. The expression levels of all tested genes were altered in all treatment groups compared to the control, with that of WNT1, CTNNB1, TCF, MTOR, AKT1, BIRC5, and CCND1 showing the most robust changes in the combined curcumin/berberine/5-FU treatment. CONCLUSIONS: All treatment groups had anti-growth, anti-invasion, and pro-apoptotic effects on MCF-7 breast cancer cells in culture. In addition, all treatment groups showed changes in the expression of the genes involved in cancer cell growth and survival with the strongest effects found for the curcumin/berberine/5-FU combination. Therefore, curcumin and berberine may improve the anticancer effects of chemotherapy and these natural compounds should undergo further testing as potential adjuvants.
Authors: Brian D Lehmann; Joshua A Bauer; Xi Chen; Melinda E Sanders; A Bapsi Chakravarthy; Yu Shyr; Jennifer A Pietenpol Journal: J Clin Invest Date: 2011-07 Impact factor: 14.808
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