title: Combined effect of papuamine and doxorubicin in human breast cancer MCF-7 cells.
abstract: Our previous study reported that an extract of an Indonesian marine sponge,Haliclonasp., showed potent cytotoxicity and induced apoptosis. The major cytotoxic chemical compound was identified as papuamine, which caused reduction of cell survival through activation of c-Jun N-terminal kinase (JNK) in human breast cancer MCF-7 cells. Doxorubicin (DOX), aStreptomycesmetabolite, is used in chemotherapy against a wide range of cancers, including breast cancer. The present study examined the combined effect of papuamine and DOX on MCF-7 cells. The effect of these reagents on cell growth was assessed by a colony formation assay. Incubation with either of the reagents alone resulted in concentration-dependent decreases in the colony formation of the MCF-7 cells. Incubation with the reagents together at sub-cytotoxic concentrations resulted in significant decreases in colony formation. The phosphorylation of JNK, the activated form of the protein, was elevated in a concentration-dependent manner upon co-incubation with papuamine and DOX. Fluorescence intensity analysis demonstrated that papuamine caused a small, but non-significant, decrease in cellular accumulation of DOX. These results indicate that the combinatory effect of papuamine and DOX is not associated with changes in the cellular accumulation of DOX, and may instead reflect additive effects on JNK activation. This study indicates that papuamine may represent a novel type of modulator for DOX chemotherapy.
authors.affiliation: Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University, Sendai 981-8558, Japan.
authors.forename: Syu-Ichi
authors.initials: SI
authors.lastname: Kanno
authors.affiliation: Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University, Sendai 981-8558, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Yomogida
authors.affiliation: Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University, Sendai 981-8558, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Tomizawa
authors.affiliation: Department of Natural Product Chemistry, Tohoku Pharmaceutical University, Sendai 981-8558, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamazaki
authors.affiliation: Department of Natural Product Chemistry, Tohoku Pharmaceutical University, Sendai 981-8558, Japan.
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Ukai
authors.affiliation: Faculty of Fisheries and Marine Science, Sam Ratulangi University, Kampus Bahu, Manado 95115, Indonesia.
authors.forename: Remy E P
authors.initials: RE
authors.lastname: Mangindaan
authors.affiliation: Department of Natural Product Chemistry, Tohoku Pharmaceutical University, Sendai 981-8558, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Namikoshi
authors.affiliation: Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University, Sendai 981-8558, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ishikawa
keywords: c-Jun N-terminal kinase; colony formation; doxorubicin; papuamine