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1.
Mol Cell Biochem ; 462(1-2): 25-31, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31440879

ABSTRACT

Resveratrol, a phytoalexin present in grapes and other edible foods, has been reported to have beneficial effects against various diseases including cancer. We previously reported that resveratrol and its derivative, caffeic acid-adducted resveratrol, selectively inhibit the three-dimensional (3D) proliferation of a human colorectal cancer cell line, HCT116 with activating KRAS mutation. Herein, we demonstrated that a novel compound, ferulic acid-bound resveratrol, also represses the 3D proliferation of HCT116 cells. We observed that resveratrol conjugated to two ferulic acids represses the 3D proliferation of HCT116 cells more strongly than resveratrol and resveratrol conjugated to one ferulic acid. Resveratrol conjugated to two ferulic acids also inhibited the 3D proliferation of MCF7 human breast cancer cells. We further uncovered that the resveratrol derivative increases the mRNA level of the tumor suppressor p15, a CDK inhibitor that functions as a brake of cell proliferation in HCT116 cells. These results imply that the resveratrol derivative represses 3D proliferation via increasing p15 expression in HCT116 cells.


Subject(s)
Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Coumaric Acids/pharmacology , Cyclin-Dependent Kinase Inhibitor p15/genetics , Genes, Tumor Suppressor , Resveratrol/pharmacology , Cell Proliferation/drug effects , Coumaric Acids/chemistry , Cyclin-Dependent Kinase Inhibitor p15/metabolism , Gene Expression Regulation, Neoplastic/drug effects , HCT116 Cells , Humans , Inhibitory Concentration 50 , MCF-7 Cells , RNA, Messenger/genetics , RNA, Messenger/metabolism , Resveratrol/chemistry
2.
Mol Cell Biochem ; 442(1-2): 39-45, 2018 May.
Article in English | MEDLINE | ID: mdl-28936721

ABSTRACT

Resveratrol is a polyphenolic compound in many edible foods including grapes, peanuts, and berries. Several studies have revealed the beneficial effects of resveratrol against various diseases such as heart disease, diabetes, obesity, neurological disorders, and cancer. A recent study showed that resveratrol inhibits the proliferation of HCT116 human colorectal cancer cells in three-dimensional culture (3DC) via induction of luminal apoptosis in HCT116 cell spheroids. In this study, we showed that a novel compound, caffeic acid-adducted resveratrol, has a stronger inhibitory effect on the growth of HCT116 cell spheroids in 3DC than resveratrol. It showed almost the same inhibitory efficacy as 5-fluorouracil, a conventional anticancer drug. We further showed that the resveratrol derivative did not affect the growth of HKe3 cell spheroids derived from HCT116 cells by disruption of the activating mutant KRAS gene. These results suggest that the resveratrol derivative inhibits the growth of HCT116 cell spheroids via inhibition of an oncogenic KRAS-mediated signaling pathway.


Subject(s)
Cell Proliferation/drug effects , Colorectal Neoplasms/metabolism , Mutation , Proto-Oncogene Proteins p21(ras)/metabolism , Signal Transduction/drug effects , Stilbenes/pharmacology , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Humans , MCF-7 Cells , Proto-Oncogene Proteins p21(ras)/genetics , Resveratrol
3.
Med Mycol J ; 56(1): J23-9, 2015.
Article in Japanese | MEDLINE | ID: mdl-25855024

ABSTRACT

A daily eatable candy that has possible protective activity against oral candidiasis was experimentally produced. The candy was made from reduced-maltose as main constituent and from several natural products, such as oligonol (depolymerized polyphenols derived from lychee), cinnamon (cassia), citral, and capric acid, which are known to have anti-Candida activity in vitro and in vivo. The candy effectively inhibited the mycelial growth of C. albicans, even when it was diluted 1,000 times with culture media. We assessed the protective activity of the candy against murine candidiasis. When 50µl of candy dissolved and diluted 4 times with water was administered 3 times into the oral cavity of Candida infected mice, the score of lesions on the Candida-infected tongues improved on day 2. These findings suggest that this candy has potential as food that provides protective activity against oral candidiasis.


Subject(s)
Candidiasis, Oral/drug therapy , Candidiasis, Oral/microbiology , Candy , Cassia/chemistry , Catechin/analogs & derivatives , Decanoic Acids/pharmacology , Monoterpenes/pharmacology , Phenols/pharmacology , Plant Extracts/pharmacology , Polyphenols/pharmacology , Acyclic Monoterpenes , Animals , Candida albicans/drug effects , Candida albicans/isolation & purification , Candidiasis, Oral/prevention & control , Catechin/pharmacology , Catechin/therapeutic use , Codonopsis/chemistry , Decanoic Acids/therapeutic use , Disease Models, Animal , Drug Combinations , Drug Resistance, Fungal , Fatty Acids/pharmacology , Fatty Acids/therapeutic use , Glycyrrhiza/chemistry , Maltose/analogs & derivatives , Mice , Mice, Inbred ICR , Monoterpenes/therapeutic use , Phenols/therapeutic use , Plant Extracts/therapeutic use , Polyphenols/therapeutic use , Propolis , Specific Pathogen-Free Organisms , Starch , Sugar Alcohols , Treatment Outcome
4.
Med Mycol J ; 56(1): J31-40, 2015.
Article in Japanese | MEDLINE | ID: mdl-25855026

ABSTRACT

In a preceding paper, we showed that aroma candy containing oligonol, capric acid, and cinnamon (cassia) powder had potent inhibitory activity against mycelial growth of Candida albicans in vitro and protective activity against murine oral candidiasis. In order to assess the effects of this candy (the test candy) on oral C. albicans colony-forming units (CFU) and oral hygiene states, a placebo-controlled double-blind crossover comparative study was performed. Twenty subjects were divided into two groups. One group ingested the test candy in the first 7 days followed by 2 weeks washing-off period, then ingested the placebo candy (control candy) for 7 days. The other group was vice versa. C. albicans CFU in all oral rinse samples from the subjects before and after 7 days ingestion of candy was measured. The degree of oral malodor in all subjects was monitored using a portable measuring instrument. The results showed no statistically significant difference between test-candy group and placebo group for C. albicans CFU. However, C. albicans CFU in test-candy group with>4,000 CFUs was significantly decreased after 7 days ingestion of test-candy (p<0.05). Scores of oral malodor in the test-candy group was significantly decreased after 7 days ingestion of test-candy (p<0.05). A questionnaire survey of oral hygiene states indicated that in the test-candy group, oral malodor, glutinous feeling, and refreshing feeling significantly improved in comparison with control-candy group (p<0.05). Our study suggests that the aroma candy is effective in oral health care of elderly carrying C. albicans.


Subject(s)
Candida albicans/isolation & purification , Candy , Cassia , Catechin/analogs & derivatives , Decanoic Acids/pharmacology , Mouth Mucosa/microbiology , Phenols/pharmacology , Aged , Catechin/administration & dosage , Catechin/pharmacology , Decanoic Acids/administration & dosage , Double-Blind Method , Female , Humans , Male , Middle Aged , Oral Hygiene , Phenols/administration & dosage , Placebo Effect , Stem Cells , Surveys and Questionnaires
5.
Biomed Res ; 33(5): 273-9, 2012.
Article in English | MEDLINE | ID: mdl-23124247

ABSTRACT

The present study examined the effects of enzymatically hydrolyzed collagen peptides on the level of hippocampal neurogenesis and emotional behavior in adult mice. For this purpose, two kinds of enzymatically hydrolyzed collagen peptides, the lower or higher molecular weight peptides (LP: below 2,000, HP: about 30,000) were administered orally to C57BL/6 mice for 4 weeks. As a result, the density of proliferating cells in subgranular zone of hippocampus showed a 1.2-fold increase in LP mice as compared with HP mice. Additionally, LP mice spent less time in closed arms than HP mice in elevated plus maze test to examine anxiety-related behavior. These results suggest that oral administration of the lower molecular weight peptides derived from collagen enhanced the hippocampal neurogenesis and exerted emotional behavior in adult mice.


Subject(s)
Anxiety/metabolism , Behavior, Animal/drug effects , Collagen/pharmacology , Hippocampus/metabolism , Neurogenesis/drug effects , Peptides/pharmacology , Animals , Cell Proliferation/drug effects , Hippocampus/cytology , Male , Maze Learning/drug effects , Mice
6.
FEBS Lett ; 540(1-3): 206-10, 2003 Apr 10.
Article in English | MEDLINE | ID: mdl-12681509

ABSTRACT

A tridecapeptide (MITLAIPVNKPGR) that stimulates phagocytosis of human neutrophils was isolated from a trypsin digest of soybean proteins. This peptide is derived from the soybean beta-conglycinin alpha' subunit and was named soymetide-13. The N-terminal methionine residue of soymetide-13 is essential for its activity, and removal of C-terminal residues revealed that soymetide-4 (MITL) is the minimal structure required for phagocytosis stimulation. Although they are not formylated at their N-termini, soymetides have a weak affinity for the N-formyl-methionyl-leucyl-phenylalanine (fMLP) receptor and their phagocytosis-stimulating activity is inhibited by the fMLP antagonist Boc-MLP. Interestingly, soymetide-4 promotes tumor necrosis factor alpha production at a higher level than soymetide-13 following oral administration in mice.


Subject(s)
Globulins/chemistry , Glycine max/chemistry , N-Formylmethionine Leucyl-Phenylalanine/agonists , Soybean Proteins/chemistry , Amino Acid Sequence , Animals , Antigens, Plant , Male , Mice , Mice, Inbred ICR , Seed Storage Proteins , Structure-Activity Relationship , Superoxides/chemistry , Tumor Necrosis Factor-alpha/biosynthesis
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