title: Anthocyanins in the black soybean (Glycine max L.) protect U2OS cells             from apoptosis by inducing autophagy via the activation of adenosyl monophosphate-dependent             protein kinase.
abstract: Anthocyanins (ATCs) have been reported to induce apoptosis in various types             of cancer cells, stimulating the development of ATCs as a cancer chemotherapeutic             or chemopreventive agent. It was recently reported that ATCs can induce autophagy,             however, the mechanism for this remains unclear. In the present report, we carried             out mechanistic studies of the mechanism involved in ATC-induced autophagy using             ATCs extracted from black soybeans (cv. Cheongja 3, Glycine max L.). ATCs clearly             induced hallmarks of autophagy, including LC3 puncta formation and the conversion             of LC3-I to LC3-II in U2OS human osteosarcoma cells. The induction of autophagy             was accompanied by the phosphorylation of multiple protein kinases including extracellular             signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK),             c-Jun N-terminal kinase (JNK), protein kinase B (AKT) and adenosyl mono-phosphate-dependent             protein kinase (AMPK). While chemical inhibitors against ERK1/2, p38 MAPK, JNK             and AKT failed to inhibit ATC-induced autophagy, the suppression of AMPK by compound             C (CC) as well as siRNA against AMPK reduced ATC-induced autophagy. The treatment             of ATCs resulted in a decrease in intracellular ATP contents and the activation             of AMPK by AICAR treatment also induced autophagy. It is noteworthy that the reduction             of autophagy via the inhibition of AMPK resulted in enhanced apoptosis in ATC-treated             cells. In addition, siRNA against forkhead box O3A (FOXO3a), a downstream target             of AMPK, suppressed ATC-induced autophagy and p27KIP1 siRNA increased apoptosis             in ATC-treated cells. Collectively, it can be concluded that ATCs induce autophagy             in U2OS cells via activation of the AMPK-FOXO3a pathway and protect cells from             ATC-induced apoptosis via the AMPK-p27KIP1 pathway. These results also suggest             that autophagy-modulating agents could contribute to the efficient development             of ATCs as anticancer therapy.
authors.affiliation: Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Yun-Jeong
authors.initials: YJ
authors.lastname: Choe
authors.forename: Tae Joung
authors.initials: TJ
authors.lastname: Ha
authors.forename: Kyoung-Won
authors.initials: KW
authors.lastname: Ko
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Seok Joon
authors.initials: SJ
authors.lastname: Shin
authors.forename: Ho-Shik
authors.initials: HS
authors.lastname: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000872:Anthocyanins / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics; D006801:Humans; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction; D013025:Glycine max / Q000737:chemistry*
chemical_list: D000872:Anthocyanins; C436291:CDKN1B protein, human; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D034741:RNA, Small Interfering; D050760:Cyclin-Dependent Kinase Inhibitor p27; D055372:AMP-Activated Protein Kinases