The Octyl Ester of Ginsenoside Rh2 Induces Lysosomal Membrane Permeabilization via Bax Translocation
Open accessAbstract
Ginsenoside Rh2 is a potential pharmacologically active metabolite of ginseng. Previously, we have reported that an octyl ester derivative of ginsenoside Rh2 (Rh2-O), has been confirmed to possess higher bioavailability and anticancer effect than Rh2 in vitro. In order to better assess the possibility that Rh2-O could be used as an anticancer compound, the underlying mechanism was investigated in this study. The present results revealed that lysosomal destabilization was involved in the early stage of cell apoptosis in HepG2 cells induced by Rh2-O. Rh2-O could induce an early lysosomal membrane permeabilization with the release of lysosomal protease cathepsins to the cytosol in HepG2 cells. The Cat B inhibitor (leu) and Cat D inhibitor (pepA) inhibited Rh2-O-induced HepG2 apoptosis as well as tBid production and Δφm depolarization, indicating that lysosomal permeabilization occurred upstream of mitochondrial dysfunction. In addition, Rh2-O induced a significant increase in the protein levels of DRAM1 and Bax (p < 0.05) in lysosomes of HepG2 cells. Knockdown of Bax partially inhibited Rh2-O-induced Cat D release from lysosomes. Thus it was concluded that Rh2-O induced apoptosis of HepG2 cells through activation of the lysosomal-mitochondrial apoptotic pathway involving the translocation of Bax to the lysosome.
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In other experimental settings, lysosomes are permeabilized before mitochondria via a mechanism that optionally involves BAX recruitment to the lysosomal membrane followed by activation of its pore-forming activity.
“In other experimental settings, however, lysosomes are permeabilized before mitochondria [752, 760, 761], via a mechanism that optionally involves BAX recruitment to the lysosomal membrane followed by the activation of its pore-forming activity [762–765].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [763]
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- Authors
- Chen, F., Zhang, B., Sun, Y., Xiong, Z.-X., Peng, H., Deng, Z.-Y., & Hu, J.-N.
- Affiliations
- Nanchang University (CN)
- State Key Laboratory of Food Science and Technology, Institute for Advanced Study, Nanchang University, Nanchang, Jiangxi 330047, China
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2016-04-25
- Volume
- 8
- Issue
- 5
- Pages
- 244
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC4882657
- OpenAlex
- W2342627490
- Cited by
- 18
- References
- 33
- Citations by year
- 2025: 3 · 2023: 1 · 2022: 4 · 2020: 6 · 2018: 3 · 2017: 1
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (31360370)
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ginseng Biological Effects and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- ginsenoside Rh2, lysosomal membrane permeabilization, Bax translocation, cathepsin B, cathepsin D, DRAM1, tBid, mitochondrial depolarization, HepG2 cells, apoptosis, anticancer activity
- MeSH terms
- Cathepsins, Cytosol, Esters, Gene Expression Regulation, Humans, Lysosomes, Membrane Proteins, Permeability, Apoptosis, Gene Silencing, Protein Transport, Ginsenosides, Cell Proliferation, bcl-2-Associated X Protein, Membrane Potential, Mitochondrial, Hep G2 Cells
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