title: Novel Evidence for Curcumin and Boswellic Acid-Induced Chemoprevention through Regulation of miR-34a and miR-27a in Colorectal Cancer.
abstract: Colorectal cancer is one of the most common causes of cancer-associated mortality worldwide, but it is truly a preventable disease. Both curcumin and boswellic acids are well-established dietary botanicals with potent antitumorigenic properties that have been shown to modulate multiple oncogenic pathways. Recent data suggest that the chemopreventive effects of these botanicals may, in part, be mediated through regulation of key cancer-related microRNAs (miRNA) and their downstream gene targets. Here, we investigated the antitumorigenic effects of curcumin and 3 acetyl-11-keto-β-boswellic acid (AKBA) on modulation of specific cancer-related miRNAs in colorectal cancer cells and validated their protective effects in vivo using a xenograft mouse model. Both curcumin and AKBA inhibited cellular proliferation, induced apoptosis and cell-cycle arrest in colorectal cancer cell lines, and these effects were significantly enhanced with combined treatment. Gene-expression arrays revealed that curcumin and AKBA regulated distinct cancer signaling pathways, including key cell-cycle regulatory genes. Combined bioinformatics and in silico analysis identified apoptosis, proliferation, and cell-cycle regulatory signaling pathways as key modulators of curcumin and AKBA-induced anticancer effects. We discovered that curcumin and AKBA induced upregulation of tumor-suppressive miR-34a and downregulation of miR-27a in colorectal cancer cells. Furthermore, we demonstrated in a mouse xenograft model that both curcumin and AKBA treatments suppressed tumor growth, which corresponded with alterations in the expression of miR-34a and miR-27a, consistent with our in vitro findings. Herein, we provide novel mechanistic evidence for the chemopreventive effects of curcumin and AKBA through regulation of specific miRNAs in colorectal cancer.
authors.affiliation: Center for Gastrointestinal Cancer Research; Center for Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute and Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas.
authors.forename: Shusuke
authors.initials: S
authors.lastname: Toden
authors.affiliation: Center for Gastrointestinal Cancer Research; Center for Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute and Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas.
authors.forename: Yoshinaga
authors.initials: Y
authors.lastname: Okugawa
authors.affiliation: Institute of Anatomy, Ludwig-Maximilian University, Munich, Germany.
authors.forename: Constanze
authors.initials: C
authors.lastname: Buhrmann
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, Texas.
authors.forename: Durgha
authors.initials: D
authors.lastname: Nattamai
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, Texas.
authors.forename: Esperanza
authors.initials: E
authors.lastname: Anguiano
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, Texas.
authors.forename: Nicole
authors.initials: N
authors.lastname: Baldwin
authors.affiliation: Institute of Anatomy, Ludwig-Maximilian University, Munich, Germany.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Shakibaei
authors.affiliation: Center for Gastrointestinal Cancer Research; Center for Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute and Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas.
authors.forename: C Richard
authors.initials: CR
authors.lastname: Boland
authors.affiliation: Center for Gastrointestinal Cancer Research; Center for Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute and Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas. ajay.goel@baylorhealth.edu.
authors.forename: Ajay
authors.initials: A
authors.lastname: Goel
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000818:Animals; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D018890:Chemoprevention / Q000379:methods; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003474:Curcumin / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D014315:Triterpenes / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: C531388:MIRN27 microRNA, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D014315:Triterpenes; C054625:boswellic acid; D003474:Curcumin