{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T01:17:17Z","timestamp":1787620637270,"version":"build-2736575974"},"reference-count":46,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,11,15]]},"abstract":"<jats:p>GGA (geranylgeranoic acid) is a natural polyprenoic acid, derivatives of which has been shown to prevent second primary hepatoma. GGA induces mitochondria-mediated PCD (programmed cell death), which may be relevant to cancer prevention. To gain further insights into GGA-induced PCD, autophagy processes were examined in human hepatoma-derived HuH-7 cells. Treatment of HuH-7\/GFP (green fluorescent protein)\u2013LC3 cells with GGA induced green fluorescent puncta in the cytoplasm within 30\u00a0min and their massive accumulation at 24\u00a0h. After 15\u00a0min of GGA treatment, a burst of mitochondrial superoxide production occurred and LC3\u03b2-I was appreciably converted into LC3\u03b2-II. GGA-induced early stages of autophagy were unequivocally confirmed by electron-microscopic observation of early\/initial autophagic vacuoles. On the other hand, LC3\u03b2-II as well as p62\/SQSTM1 (sequestosome 1) continuously accumulated and co-localized in the cytoplasmic puncta after GGA treatment. Furthermore, GGA treatment of HuH-7\/mRFP (monomeric red fluorescent protein)\u2013GFP\u2013LC3 cells showed yellow fluorescent puncta, whereas glucose deprivation of the cells gave red fluorescent puncta. These results strongly suggest that GGA induces the initial phase of autophagy, but blocks the maturation process of autolysosomes or late stages of autophagy, insomuch that GGA provides substantial accumulation of autophagosomes under serum-starvation conditions in human hepatoma cells.<\/jats:p>","DOI":"10.1042\/bj20110610","type":"journal-article","created":{"date-parts":[[2011,7,28]],"date-time":"2011-07-28T04:46:41Z","timestamp":1311828401000},"page":"63-71","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Induction of an incomplete autophagic response by cancer-preventive geranylgeranoic acid (GGA) in a human hepatoma-derived cell line"],"prefix":"10.1042","volume":"440","author":[{"given":"Kyoko","family":"Okamoto","sequence":"first","affiliation":[{"name":"Molecular and Cellular Biology, Graduate School of Human Health Sciences, Siebold University of Nagasaki, Nagasaki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Sakimoto","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology, Graduate School of Human Health Sciences, Siebold University of Nagasaki, Nagasaki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuyuki","family":"Imai","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Histology, Akita University School of Medicine, Akita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruki","family":"Senoo","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Histology, Akita University School of Medicine, Akita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Shidoji","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology, Graduate School of Human Health Sciences, Siebold University of Nagasaki, Nagasaki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2011,10,27]]},"reference":[{"key":"2021112215191482700_B1","first-page":"974","article-title":"In vitro binding affinity of novel synthetic polyprenoids (polyprenoic acids) to cellular retinoid-binding proteins","volume":"72","author":"Muto","year":"1981","journal-title":"Gann"},{"key":"2021112215191482700_B2","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1006\/bbrc.1995.1471","article-title":"Retinoid agonist activities of synthetic geranylgeranoic acid derivatives","volume":"209","author":"Araki","year":"1995","journal-title":"Biochem. 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