title: The Antiproliferative Effect of Chakasaponins I and II, Floratheasaponin A, and Epigallocatechin 3-O-Gallate Isolated from Camellia sinensis on Human Digestive Tract Carcinoma Cell Lines.
abstract: Acylated oleanane-type triterpene saponins, namely chakasaponins I (1) and II (2), floratheasaponin A (3), and their analogs, together with catechins-including (-)-epigallocatechin 3-O-gallate (4), flavonoids, and caffeine-have been isolated as characteristic functional constituents from the extracts of "tea flower", the flower buds ofCamellia sinensis(Theaceae), which have common components with that of the leaf part. These isolates exhibited antiproliferative activities against human digestive tract carcinoma HSC-2, HSC-4, MKN-45, and Caco-2 cells. The antiproliferative activities of the saponins (1-3, IC50= 4.4-14.1, 6.2-18.2, 4.5-17.3, and 19.3-40.6 µM, respectively) were more potent than those of catechins, flavonoids, and caffeine. To characterize the mechanisms of action of principal saponin constituents1-3, a flow cytometric analysis using annexin-V/7-aminoactinomycin D (7-AAD) double staining in HSC-2 cells was performed. The percentage of apoptotic cells increased in a concentration-dependent manner. DNA fragmentation and caspase-3/7 activation were also detected after 48 h. These results suggested that antiproliferative activities of1-3induce apoptotic cell death via activation of caspase-3/7.
authors.affiliation: Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan. kitagawa@koshiroseiyaku.co.jp.|Koshiro Company Ltd., 2-5-8 Doshomachi, Chuo-ku, Osaka 541-0045, Japan. kitagawa@koshiroseiyaku.co.jp.
authors.forename: Niichiro
authors.initials: N
authors.lastname: Kitagawa
authors.affiliation: Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan. morikawa@kindai.ac.jp.|Antiaging Center, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan. morikawa@kindai.ac.jp.
authors.forename: Toshio
authors.initials: T
authors.lastname: Morikawa
authors.affiliation: Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan. motai@koshiroseiyaku.co.jp.|Koshiro Company Ltd., 2-5-8 Doshomachi, Chuo-ku, Osaka 541-0045, Japan. motai@koshiroseiyaku.co.jp.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Motai
authors.affiliation: Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan. ninomiya@phar.kindai.ac.jp.|Antiaging Center, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan. ninomiya@phar.kindai.ac.jp.
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Ninomiya
authors.affiliation: Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan. okugawa_kameokanousan@koshiroseiyaku.co.jp.|Koshiro Company Ltd., 2-5-8 Doshomachi, Chuo-ku, Osaka 541-0045, Japan. okugawa_kameokanousan@koshiroseiyaku.co.jp.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Okugawa
authors.affiliation: Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan. 1311610173m@kindai.ac.jp.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Nishida
authors.affiliation: Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan. m-yoshikawa@leto.eonet.ne.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yoshikawa
authors.affiliation: Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan. muraoka@phar.kindai.ac.jp.|Antiaging Center, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan. muraoka@phar.kindai.ac.jp.
authors.forename: Osamu
authors.initials: O
authors.lastname: Muraoka
mesh_terms: D028241:Camellia sinensis / Q000737:chemistry*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D035264:Flowers / Q000737:chemistry; D006801:Humans; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D012503:Saponins / Q000494:pharmacology*
chemical_list: D010936:Plant Extracts; D012503:Saponins; C575525:chakasaponin I; C575526:chakasaponin II; C505301:floratheasaponin A; D009828:Oleanolic Acid; D002392:Catechin; C045651:epigallocatechin gallate; D053148:Caspase 3; D053179:Caspase 7
keywords: (–)-epigallocatechin 3-O-gallate; Camellia sinensis; anti-proliferative activity; apoptosis; chakasaponin; floratheasaponin; tea flower