Identification of Anhydrodebromoaplysiatoxin as a Dichotomic Autophagy Inhibitor

Limin Feng; Chung-Kuang Lu; Jiajun Wu; Leo Lai Chan; Jianbo Yue

doi:10.3390/md21010046

Identification of Anhydrodebromoaplysiatoxin as a Dichotomic Autophagy Inhibitor

Limin Feng, Chung-Kuang Lu, Jiajun Wu, Leo Lai Chan^*, Jianbo Yue^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

3 Citations (Scopus)

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Abstract

Dysfunctional autophagy is associated with various human diseases, e.g., cancer. The discovery of small molecules modulating autophagy with therapeutic potential could be significant. To this end, we screened the ability of a series of metabolites isolated from marine microorganisms to modulate autophagy. Anhydrodebromoaplysiatoxin (ADAT), a metabolite yielded by the marine red algae Gracilaria coronopifolia, inhibited autophagosome-lysosome fusion in mammalian cells, thereby inducing the accumulation of autophagosomes. Treatment of cells with ADAT alkalinized lysosomal pH. Interestingly, ADAT also activated the mTOR/p70S6K/FoxO3a signaling pathway, likely leading to the inhibition of autophagy induction. ADAT had little effect on apoptosis. Our results suggest that ADAT is a dichotomic autophagy inhibitor that inhibits both late-stage (autophagosome-lysosome fusion) and early-stage (autophagy induction) autophagy.

© 2023 by the authors.

Original language	English
Article number	46
Journal	Marine Drugs
Volume	21
Issue number	1
Online published	10 Jan 2023
DOIs	https://doi.org/10.3390/md21010046
Publication status	Published - Jan 2023

Research Keywords

anhydrodebromoaplysiatoxin
autophagy
mTOR
FoxO3a
lysosome
PROTEIN-KINASE-C
TUMOR PROMOTERS
CELL APOPTOSIS
APLYSIATOXIN
ACTIVATION
PI3K/AKT/MTOR/P70S6K
DEBROMOAPLYSIATOXIN
TELEOCIDIN
RED

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This full text is made available under CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Identification of Anhydrodebromoaplysiatoxin as a Dichotomic Autophagy Inhibitor",

abstract = "Dysfunctional autophagy is associated with various human diseases, e.g., cancer. The discovery of small molecules modulating autophagy with therapeutic potential could be significant. To this end, we screened the ability of a series of metabolites isolated from marine microorganisms to modulate autophagy. Anhydrodebromoaplysiatoxin (ADAT), a metabolite yielded by the marine red algae Gracilaria coronopifolia, inhibited autophagosome-lysosome fusion in mammalian cells, thereby inducing the accumulation of autophagosomes. Treatment of cells with ADAT alkalinized lysosomal pH. Interestingly, ADAT also activated the mTOR/p70S6K/FoxO3a signaling pathway, likely leading to the inhibition of autophagy induction. ADAT had little effect on apoptosis. Our results suggest that ADAT is a dichotomic autophagy inhibitor that inhibits both late-stage (autophagosome-lysosome fusion) and early-stage (autophagy induction) autophagy.{\textcopyright} 2023 by the authors.",

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author = "Limin Feng and Chung-Kuang Lu and Jiajun Wu and Chan, {Leo Lai} and Jianbo Yue",

year = "2023",

month = jan,

doi = "10.3390/md21010046",

language = "English",

volume = "21",

journal = "Marine Drugs",

issn = "1660-3397",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "1",

}

TY - JOUR

T1 - Identification of Anhydrodebromoaplysiatoxin as a Dichotomic Autophagy Inhibitor

AU - Feng, Limin

AU - Lu, Chung-Kuang

AU - Wu, Jiajun

AU - Chan, Leo Lai

AU - Yue, Jianbo

PY - 2023/1

Y1 - 2023/1

N2 - Dysfunctional autophagy is associated with various human diseases, e.g., cancer. The discovery of small molecules modulating autophagy with therapeutic potential could be significant. To this end, we screened the ability of a series of metabolites isolated from marine microorganisms to modulate autophagy. Anhydrodebromoaplysiatoxin (ADAT), a metabolite yielded by the marine red algae Gracilaria coronopifolia, inhibited autophagosome-lysosome fusion in mammalian cells, thereby inducing the accumulation of autophagosomes. Treatment of cells with ADAT alkalinized lysosomal pH. Interestingly, ADAT also activated the mTOR/p70S6K/FoxO3a signaling pathway, likely leading to the inhibition of autophagy induction. ADAT had little effect on apoptosis. Our results suggest that ADAT is a dichotomic autophagy inhibitor that inhibits both late-stage (autophagosome-lysosome fusion) and early-stage (autophagy induction) autophagy.© 2023 by the authors.

AB - Dysfunctional autophagy is associated with various human diseases, e.g., cancer. The discovery of small molecules modulating autophagy with therapeutic potential could be significant. To this end, we screened the ability of a series of metabolites isolated from marine microorganisms to modulate autophagy. Anhydrodebromoaplysiatoxin (ADAT), a metabolite yielded by the marine red algae Gracilaria coronopifolia, inhibited autophagosome-lysosome fusion in mammalian cells, thereby inducing the accumulation of autophagosomes. Treatment of cells with ADAT alkalinized lysosomal pH. Interestingly, ADAT also activated the mTOR/p70S6K/FoxO3a signaling pathway, likely leading to the inhibition of autophagy induction. ADAT had little effect on apoptosis. Our results suggest that ADAT is a dichotomic autophagy inhibitor that inhibits both late-stage (autophagosome-lysosome fusion) and early-stage (autophagy induction) autophagy.© 2023 by the authors.

KW - anhydrodebromoaplysiatoxin

KW - autophagy

KW - mTOR

KW - FoxO3a

KW - lysosome

KW - PROTEIN-KINASE-C

KW - TUMOR PROMOTERS

KW - CELL APOPTOSIS

KW - APLYSIATOXIN

KW - ACTIVATION

KW - PI3K/AKT/MTOR/P70S6K

KW - DEBROMOAPLYSIATOXIN

KW - TELEOCIDIN

KW - RED

UR - http://gateway.isiknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=LinksAMR&SrcApp=PARTNER_APP&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000917681600001

U2 - 10.3390/md21010046

DO - 10.3390/md21010046

M3 - RGC 21 - Publication in refereed journal

C2 - 36662219

SN - 1660-3397

VL - 21

JO - Marine Drugs

JF - Marine Drugs

IS - 1

M1 - 46

ER -

Identification of Anhydrodebromoaplysiatoxin as a Dichotomic Autophagy Inhibitor

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Research Keywords

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ITF: Autologous-Allogeneic Human Peripheral CAK-NK Cells Construction and Combination with Immune Checkpoint Inhibitors on Treatment of Genitourinary Tumors: Key Technology Innovation, Efficacy and Mechanistic Study

ITF: Development of Bisbenzylisoquinoline Alkaloid-Berbamine and Its Analogs to Prevent and Treat COVID-19 by Compromising the Endosome-lysosome Transport of ACE2

ITF: Development of a Novel Therapeutic to Promote Anticancer Immunity by Manipulating Endosomal Trafficking of PD-L1

Cite this

Identification of Anhydrodebromoaplysiatoxin as a Dichotomic Autophagy Inhibitor

Abstract

Research Keywords

Publisher's Copyright Statement

UN SDGs

Access Output

Other Access Options

Permanent Link

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Projects

ITF: Autologous-Allogeneic Human Peripheral CAK-NK Cells Construction and Combination with Immune Checkpoint Inhibitors on Treatment of Genitourinary Tumors: Key Technology Innovation, Efficacy and Mechanistic Study

ITF: Development of Bisbenzylisoquinoline Alkaloid-Berbamine and Its Analogs to Prevent and Treat COVID-19 by Compromising the Endosome-lysosome Transport of ACE2

ITF: Development of a Novel Therapeutic to Promote Anticancer Immunity by Manipulating Endosomal Trafficking of PD-L1

Cite this