Regulation of lysosomal autophagy in transformed and non-transformed mouse fibroblasts under several growth conditions*1

Knecht, Erwin; Hernández-Yago, José; Grisolı́a, Santiago

doi:10.1016/0014-4827(84)90682-7

Cited by 57 publications

(41 citation statements)

References 26 publications

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“…The implication of autophagy in cancer therapy is controversial in terms of whether autophagy plays a protective or detrimental role in cancer cells. However, reduced autophagic activity has been reported in certain types of cancer cells (15,16). Several natural compounds, such as arsenic trioxide, soybean B-group triterpenoid saponins or curcumin, have been shown to induce autophagy in a variety of tumor cells (17)(18)(19)(20).…”

Section: Discussionmentioning

confidence: 99%

Resveratrol-induced autophagy in human U373 glioma cells

Yamamoto¹,

Suzuki²,

Himeno³

2010

Oncology Letters

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Abstract. Autophagy is an intracellular protein transport process leading to the degradation of organelles and long-lived proteins in eukaryotes. The down-regulation of autophagy observed in cancer cells has been associated with tumor progression. This study investigated autophagy induced by resveratrol, a natural compound, in human glioma cells. Glioma cells were exposed to resveratrol, and the cell growth and autophagic level were evaluated. Resveratrol inhibited growth and induced cell death in U373 glioma cells. When treated with resveratrol, glioma cells stably expressing GFP fused to LC3, recruited more GFP-LC3-labeled autophagosomes, and the percentage of cells with GFP-LC3-labeled autophagosomes increased. Furthermore, in resveratroltreated glioma cells, pretreatment with P38 or ERK1/2 inhibitors reduced the autophagic level, suggesting that resveratrol-induced autophagy was positively regulated by P38 and the ERK1/2 pathway. The Akt/mTOR pathway was not involved in resveratrol-induced autophagy. Our results suggest that resveratrol has an anticancer effect on glioma cells by inducing autophagy.

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Section: Discussionmentioning

confidence: 99%

Resveratrol-induced autophagy in human U373 glioma cells

Yamamoto¹,

Suzuki²,

Himeno³

2010

Oncology Letters

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“…In the liver, proteasomes were localized both within dense bodies and within vacuoles belonging to the autophagic-lysosomal system (autophagosomes and autolysosomes), clearly identifiable by electron microscopy morphological criteria (Kovacs et al, 1981; Mortimore et al, 1983;Knecht et al, 1984). Immunoblot analysis with affinity-purified anti-proteasome IgG of a lysosomal fraction enriched in autophagic vacuoles (as judged by electron microscopy, not shown) and a standard lysosomal fraction (Fig.…”

Section: Mechanisms Of Proteasome Uptake By Lysosomesmentioning

confidence: 90%

“…Also, treatment with vinblastine, which increases the amount of autophagic vacuoles, showed by immunoblot and immunogold analysis that, both under fed and starvation conditions, proteasomes were found associated to autophagic vacuoles and dense bodies (data not shown). Dense bodies are generally considered residual bodies (Kovacs et al, 1981) but some of them may participate in microautophagy (Mortimore et al, 1983;Knecht et al, 1984) and probably also in other lysosomal processes. Under conditions of starvation, a selective transport of proteins containing KFERQ-like peptide motifs into lysosomes is believed to occur (Wing et al, 1991).…”

Section: Mechanisms Of Proteasome Uptake By Lysosomesmentioning

confidence: 99%

Degradation of Proteasomes by Lysosomes in Rat Liver

Cuervo

Palmer

Rivett

et al. 1995

European Journal of Biochemistry

102

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Proteasomes are high-molecular-mass multisubunit complexes which are believed, either by themselves or as a part of the 26s proteinase complex, to play a central role in extralysosomal pathways of intracellular protein breakdown. We have addressed the degradation of proteasomes in rat liver, investigating the possible role of lysosomes. Affinity-purified antibodies against rat liver proteasomes were used for inimunoblot analysis of isolated lysosomes. Although proteasomes are not found in lysosomes from normally fed rats, they were found to accumulate in lysosomes of rats treated with leupeptin (an inhibitor of lysosomal proteases) and could also be detected in lysosomes isolated from livers of starved (24 h) rats. Proteinase-K treatment of these fractions, as well as immunogold procedures, show that a proportion of the proteasomes are inside lysosomes. Comparison of the amount of proteasomes found in lysosomes by irnmunoblotting with their experimentally determined half life (8.3 days) is consistent with an important role of these organelles in the degradation of rat liver proteasomes. Nevertheless, these data do not exclude the possibility that some nonlysosomal degradation of proteasome components also occurs. Since proteasomes were localized in autophagic vacuoles, it is likely that they are taken up mainly by nonselective autophagy. However, using an in vitro system, it was found that, under conditions of starvation, proteasomes may also be taken up into lysosomes and degraded via the heat-shock cognate protein of 73 MEa (hsc73)-mediated transport.

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“…특히 정상세포에 비하여 암세포에서는 autophagy 의 활성이 매우 약하게 발현되고 있는 것으로 보고되고 있으며, 암세포의 성장환경 중 세포가 매우 밀집되거나 serum 및 아미노산이 결핍되었을 경우 autophagy의 활성 이 증가되어 세포사를 유도할 수 있을 것으로 보고된 바 있다. 즉 transformed cell의 경우 nutrient 및 serum의 결핍 상태에서 autophagy가 활성화되어 protein이 degradation되 어 세포사가 나타나는 것으로 많은 연구자에 의하여 관 찰되었다 (Gunn et al 1977;Lockwood and Minassian 1982;Cockle and Dean 1984;Gronostajski and Pardee 1984;Knecht et al 1984).…”

Section: Autophagy와 암세포unclassified

Autophagy: Noble target mechanisms in natural medicines as anticancer agents

Kang¹

2010

Journal of Plant Biotechnology

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Programmed cell death systems are important for an active type of cell deaths. Among them, a type of programmed cell death, autophagy is activated in cancer cells in response to multiple stresses and has been demonstrated to promote tumor cell survival and drug resistance. Thus, in the area of cancer, over the time frame form around the 1940s to date, of the 155 small molecules, 73% are other than "synthetic", with 47% actually being either "natural products" or "directly derived therefrom". Autophagy has multiple physiological functions in multicellular organisms, including protein degradation and organelle turnover. Genes and proteins that constitute the basic machinery of the autophagic process were first identified in the yeast system and some of their mammalian orthologues have been characterized as well. Numerous oncogenes, including Akt1, Bcl-2, NF1, PDPK1, class I PI3K, PTEN, and Ras and oncosuppressors, inculuding Bec-1, Bif-1, DAPK-1, p53 and UVRAG suppress or promote the autophagy pathway. Regulation of autophagy in tumors is governed by similar principles of the normal cells, only in a much more complicated manner, given the frequently observed abnormal PI3K activation in cancer and the multitude of interactions between the PI3K/ AKT/mTOR pathway and other cell signaling cascades, often also deregulated in tumor cells. Autophagy induction by some anticancer agents underlines the potential utility of its induction as a new cancer treatment modality of development for natural medicines.

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Regulation of lysosomal autophagy in transformed and non-transformed mouse fibroblasts under several growth conditions*1

Cited by 57 publications

References 26 publications

Resveratrol-induced autophagy in human U373 glioma cells

Resveratrol-induced autophagy in human U373 glioma cells

Degradation of Proteasomes by Lysosomes in Rat Liver

Autophagy: Noble target mechanisms in natural medicines as anticancer agents

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