title: In vitro anticancer activity of methyl caffeate isolated from Solanum torvum Swartz. fruit.
abstract: The present study was undertaken to investigate the anticancer activity of methyl caffeate isolated from Solanum torvum Swartz. fruit and to explore the molecular mechanisms of action in MCF-7 cells. Cytotoxic properties of hexane, ethyl acetate and methanol extracts were carried out against MCF-7 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Ethyl acetate extract showed good cytototoxic activities compared to hexane and methanol extracts. Methyl caffeate was isolated from the ethyl acetate extract using column chromatography. Cytotoxic properties of methyl caffeate was investigated against MCF-7, A549, COLO320, HepG-2 and Vero cells. The compound showed potent cytotoxic properties against MCF-7 cells compared to A549, COLO320 and HepG-2 cells. Methyl caffeate significantly reduced cell proliferation and increased formation of fragmented DNA and apoptotic body in MCF-7 cells. Bcl-2, Bax, Bid, p53, caspase-3, PARP and cytochrome c release were detected by western blot analysis. The activities of caspases-3 and PARP gradually increased after the addition of isolated compound. Bcl-2 protein was down regulated; Bid and Bax were up regulated after the treatment with methyl caffeate. Molecular docking studies showed that the compound bound stably to the active sites of poly (ADP-ribose) polymerase-1 (PARP1), B cell CLL/lymphoma-2 (BCL-2), E3 ubiquitin-protein ligase (MDM2) and tubulin. The results strongly suggested that methyl caffeate induced apoptosis in MCF-7 cells via caspase activation through cytochrome c release from mitochondria.
authors.affiliation: Department of Hematology, Fujita Health University, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan; Division of Cancer Biology, Entomology Research Institute, Loyola College, Chennai 600 034, India. Electronic address: balasang@fujita-hu.ac.jp.
authors.forename: C
authors.initials: C
authors.lastname: Balachandran
authors.affiliation: Department of Hematology, Fujita Health University, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Emi
authors.affiliation: Organic & Bio-organic Chemistry Laboratory, CSIR-Central Leather Research Institute, Chennai 600 020, India.
authors.forename: Y
authors.initials: Y
authors.lastname: Arun
authors.affiliation: Department of Hematology, Fujita Health University, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Division of Cancer Biology, Entomology Research Institute, Loyola College, Chennai 600 034, India.
authors.forename: B
authors.initials: B
authors.lastname: Ahilan
authors.affiliation: Department of Toxicology, Advinus Therapeutics Ltd, Bangalore 560058, India.
authors.forename: B
authors.initials: B
authors.lastname: Sangeetha
authors.affiliation: Department of Botany and Microbiology, Addiriya Chair for Environmental Studies, College of Science, King Saud University, P.O.Box.2455, Riyadh 11451, Saudi Arabia.
authors.forename: V
authors.initials: V
authors.lastname: Duraipandiyan
authors.affiliation: Department of Hematology, Fujita Health University, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Inaguma
authors.affiliation: Department of Hematology, Fujita Health University, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: Akinao
authors.initials: A
authors.lastname: Okamoto
authors.affiliation: Division of Cancer Biology, Entomology Research Institute, Loyola College, Chennai 600 034, India.
authors.forename: S
authors.initials: S
authors.lastname: Ignacimuthu
authors.affiliation: Department of Botany and Microbiology, Addiriya Chair for Environmental Studies, College of Science, King Saud University, P.O.Box.2455, Riyadh 11451, Saudi Arabia.
authors.forename: N A
authors.initials: NA
authors.lastname: Al-Dhabi
authors.affiliation: Organic & Bio-organic Chemistry Laboratory, CSIR-Central Leather Research Institute, Chennai 600 020, India.
authors.forename: P T
authors.initials: PT
authors.lastname: Perumal
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002109:Caffeic Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D002522:Chlorocebus aethiops; D045304:Cytochromes c / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005638:Fruit / Q000737:chemistry; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D062105:Molecular Docking Simulation; D032322:Solanum / Q000737:chemistry*; D014709:Vero Cells / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002109:Caffeic Acids; C042405:methyl caffeate; D045304:Cytochromes c; D020169:Caspases
keywords: Caspases; Cytochrome c; Molecular docking; Solanum torvum; p53