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Cited by 70Magnolia and Illicium researchAutophagy in Disease and TherapyCell death mechanisms and regulation

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Honokiol activates reactive oxygen species-mediated cytoprotective autophagy in human prostate cancer cells: Honokiol Induces Cytoprotective Autophagy

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Hahm, Eun-Ryeong, Sakao, Kozue, Singh, Shivendra V.·2014·The Prostate
DOI 10.1002/pros.22837PMC PMC4156520
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Abstract

BACKGROUND: Honokiol (HNK), derived from the bark of an oriental medicinal plant (Magnolia officinalis), is a promising anticancer agent with preclinical in vitro (PC-3 and LNCaP cells) and in vivo (PC-3 xenografts) efficacy against prostate cancer. However, the mechanisms affecting anticancer response to HNK are not fully understood. METHODS: Human (androgen-independent PC-3 and androgen-responsive LNCaP) and murine (Myc-CaP) prostate cancer cells, and PC-3 tumor xenografts were used for various assays. Autophagy was assessed by transmission electron microscopy, immunofluorescence (LC3 puncta), and immunoblotting (LC3BII detection). Cell viability was determined by trypan blue assay. Apoptosis was quantitated by DNA fragmentation detection and Annexin V/propidium iodide assay. Reactive oxygen species (ROS) were detected by electron paramagnetic resonance spectrometry and flow cytometric/microscopic analysis of MitoSOX red fluorescence. RESULTS: Exposure of PC-3, LNCaP, and Myc-CaP cells to pharmacologic doses of HNK resulted in autophagy induction. The PC-3 tumor xenografts from HNK-treated mice contained higher levels of LC3BII protein compared with control tumors. Cell viability inhibition and apoptosis induction resulting from HNK exposure were significantly augmented by pharmacological inhibition of autophagy using 3-methyladenine as well as RNA interference of autophagy regulator ATG5. HNK-mediated increase in levels of LC3BII protein was partially but markedly diminished in the presence of antioxidants, including N-acetylcysteine, polyethylene glycol-conjugated (PEG)-superoxide dismutase, and PEG-catalase. On the other hand, antioxidants had no impact on HNK-induced apoptosis. CONCLUSIONS: In conclusion, the present study demonstrates, for the first time, that HNK induces ROS-mediated cytoprotective autophagy in prostate cancer cells.

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Metadata

Authors
Hahm, E.-R., Sakao, K., & Singh, S. V.
Affiliations
  • University of Pittsburgh (US)
  • Kagoshima University (JP)
Corresponding author
Singh, Shivendra V.
ORCID
Venue
The Prostate
Publisher
Wiley
Published
2014-07-07
Volume
74
Issue
12
Pages
1209-1221
ISSN
0270-4137 (ISSN-L)
DOI
10.1002/pros.22837
PMC
PMC4156520
OpenAlex
W1531380847
Cited by
70
References
1
Citations by year
2026: 1 · 2025: 5 · 2024: 2 · 2022: 6 · 2021: 4 · 2020: 5 · 2019: 11 · 2018: 8 · 2017: 11 · 2016: 8 · 2015: 8 · 2014: 1
FWCI
9.06
Type
journal article
Language
en
Open access
Licence
Locations
  • The Prostate (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Cancer Institute (RO1 CA101753-10, RO1 CA115498-08, RO1 CA113363-10)
  • National Cancer Institute at the National Institutes of Health (P30 CA047904)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Magnolia and Illicium research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
honokiol, prostate cancer, autophagy, reactive oxygen species, cytoprotective autophagy, apoptosis, ATG5, antioxidants, Magnolia officinalis, anticancer agents, PC-3 cells, LNCaP cells, 3-methyladenine
MeSH terms
Allyl Compounds, Animals, Autophagy, Biphenyl Compounds, Drugs, Chinese Herbal, Humans, Male, Mice, Transgenic, Phenols, Prostatic Neoplasms, Reactive Oxygen Species, Lignans, Cytoprotection, Cell Line, Tumor, Mice

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