title: Sugar-dependent aggregation of glycoconjugated chlorins and its effect on photocytotoxicity in HeLa cells.
abstract: In order to explore the influence of the sugar moieties of glycoconjugated chlorins on the photocytotoxicity, we studied the photochemical properties of four glycoconjugated chlorins in aqueous media such as cytoplasm and the concentration dependence of photocytotoxicity in HeLa cells. In phosphate-buffered saline, the fluorescence intensities of 5,10,15,20-tetrakis[3-(beta-D-glucopyranosyloxy)phenyl]chlorin (m-1a) and 5,10,15,20-tetrakis[3-(beta-D-galactopyranosyloxy)phenyl]chlorin (m-1b), i.e., chlorins having hexose groups, were about 2-fold greater than those of 5,10,15,20-tetrakis[3-(beta-d-xylopyranosyloxy)phenyl]chlorin (m-1c) and 5,10,15,20-tetrakis[3-(beta-d-arabinopyranosyloxy)phenyl]chlorin (m-1d), i.e., chlorins having pentose groups, owing to a sugar-dependent difference of aggregation behavior. While no cytotoxicity was found in the dark, the highest photocytotoxicity was shown by m-1a (82% inhibition) in HeLa cells. This was higher than those of m-1b, m-1c, m-1d and tetraphenylporphyrin tetrasulfonic acid. The glycoconjugated chlorins except for m-1b appeared to be distributed diffusely throughout the cytoplasm. Among the four photosensitizers, m-1a showed the highest intensity in confocal fluorescence images, in agreement with the in vitro photocytotoxicity results. For m-1c, no photocytotoxicity was found at drug concentrations from 0.2 to 0.04 microM. Hence, sugar-dependent aggregation is not the major reason for the unexpected lack of efficacy of m-1c, which is uptaken efficiently by HeLa cells. For the glycoconjugated chlorins, these results suggest the biological aspects of sugar moiety play much crucial role rather than chemical aspects.
authors.affiliation: Division of Material Science, Graduate School of Human Culture, Nara Women's University, Kitauoyanishimachi, Nara 630-8506, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Hirohara
authors.forename: Makoto
authors.initials: M
authors.lastname: Obata
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Ogata
authors.forename: Kazumi
authors.initials: K
authors.lastname: Kajiwara
authors.forename: Chikara
authors.initials: C
authors.lastname: Ohtsuki
authors.forename: Masao
authors.initials: M
authors.lastname: Tanihara
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Yano
mesh_terms: D001692:Biological Transport; D002241:Carbohydrates / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006001:Glycoconjugates / Q000737:chemistry* / Q000494:pharmacology; D006031:Glycosylation; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D015394:Molecular Structure; D010777:Photochemistry; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000494:pharmacology; D011166:Porphyrins / Q000737:chemistry* / Q000494:pharmacology; D012996:Solutions / Q000737:chemistry; D013057:Spectrum Analysis; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D014867:Water / Q000737:chemistry
chemical_list: D002241:Carbohydrates; D006001:Glycoconjugates; D017319:Photosensitizing Agents; D011166:Porphyrins; D012996:Solutions; D014867:Water; C006969:chlorin