[6]-Shogaol, a dietary phenolic compound, induces oxidative stress mediated mitochondrial dependant apoptosis through activation of proapoptotic factors in Hep-2 cells

Annamalai, Govindhan; Suresh, K.; Kannappan, N.

doi:10.1016/j.biopha.2016.04.044

Cited by 57 publications

(61 citation statements)

References 53 publications

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“…It was reported that 6‐gingerol attenuated oxidative damage on cell death of neurons (Lee, Park, Kim, & Jang, ), while it damaged the mitochondrial function resulting in cellular apoptosis in several other cell types (Mansingh, O J, Sali, & Vasanthi, ; Nigam, Bhui, Prasad, George, & Shukla, ; Yang et al., ). 6‐Shogaol was consistently reported to damage mitochondrial function of cells (Annamalai, Kathiresan, & Kannappan, ; Chen et al., ; Warin, Chen, Soroka, Zhu, & Sang, ). We hypothesized that the concentration of 6‐gingerol and 6‐shogaol used in various experimental settings may cause the above inconsistency.…”

Section: Discussionmentioning

confidence: 99%

Promotion of Mitochondrial Biogenesis via Activation of AMPK‐PGC1ɑ Signaling Pathway by Ginger (Zingiber officinale Roscoe) Extract, and Its Major Active Component 6‐Gingerol

Deng

Zhang

et al. 2019

Journal of Food Science

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Several studies indicated that ginger (Zingiber officinale Roscoe) enhances thermogenesis and/or energy expenditure with which to interpret the beneficial effects of ginger on metabolic disorders. It is well known that mitochondrial activity plays an essential role in these processes. Thus, this study aimed to investigate the effect of ginger extract (GE) and its major components, 6‐gingerol and 6‐shogaol, on mitochondrial biogenesis and the underlying molecular mechanisms. Our results showed that GE at dose of 2 g/kg promoted oxygen consumption and intrascapular temperature in mice. The mitochondrial DNA (mtDNA) copy number in muscle and liver increased. Expression levels of oxidative phosphorylation (OXPHOS) related proteins and AMP‐activated protein kinase ɑ/proliferator‐activated receptor gamma coactivator 1 ɑ (AMPK/PGC1ɑ) signaling related proteins in the muscle, liver, and brown adipose tissue (BAT) increased as well. In HepG2 cells, GE at concentration of 2.5 and 5 mg/mL increased mitochondrial mass and mtDNA copy number. GE promoted ATP production, the activities of mitochondrial respiratory chain complex I and IV, and expression levels of OXPHOS complex related proteins and AMPK/PGC1ɑ signaling related proteins. The antagonist of AMPK eliminated partly the effect of GE on mitochondrial biogenesis. 6‐Gingerol increased mitochondrial mass, mtDNA copy number and ATP production, and the activities of mitochondrial respiratory chain complexes in HepG2 cells as well. However, both 6‐gingerol at high concentration of 200 µM and 6‐shogaol at 10 to 200 µM inhibited cell viability. In conclusion, GE promoted mitochondrial biogenesis and improved mitochondrial functions via activation of AMPK‐PGC1ɑ signaling pathway, and 6‐gingerol other than 6‐shogaol, may be the main active component. Practical Application Ginger (Zingiber officinale Roscoe) is a food seasoning and also used as a medical plant in alternative medicine throughout the world. Here, we demonstrated that ginger extract (GE) promoted mitochondrial biogenesis and mitochondrial function via activation of AMPK‐PGC1ɑ signaling pathway both in mice and in HepG2 cells, and 6‐gingerol may be its main active component. Ginger, with anticipated safety, is expected to be a long‐term used dietary supplement and be developed into a new remedy for mitochondrial dysfunctional disorders.

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Section: Discussionmentioning

confidence: 99%

Promotion of Mitochondrial Biogenesis via Activation of AMPK‐PGC1ɑ Signaling Pathway by Ginger (Zingiber officinale Roscoe) Extract, and Its Major Active Component 6‐Gingerol

Deng

Zhang

et al. 2019

Journal of Food Science

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“…In this study, the role of ROS in ZO‐induced apoptotic cell death of HCT116 cells was established by pretreatment with NAC, an ROS scavenger, and the subsequent restoration of cell viability (Figure C). Thus the overgeneration of ROS leads to enhance lipid peroxidation levels and subsequently diminished antioxidant levels in ZO‐treated cancer cells in agreement with a previous report on ginger ingredients of shogaol in Hep‐2 cell lines …”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, ZO induced apoptotic features, such as chromatin condensation, nuclear disintegration, membrane blebbing, and apoptotic cell death, as confirmed by AO/EtBr and Hoechst staining. Similarly, a ginger‐derived phenolic agent of shogaol induced oxidative DNA damage–mediated apoptosis in Hep‐2 cells . Another study documented that Ginger Oleoresin alleviated γ‐ray irradiation–induced ROS via the Nrf2 protective response in human mesenchymal stem cells…”

Section: Discussionmentioning

confidence: 99%

“…The MMP was determined by Rh‐123, lipophilic cationic dye . The cells were seeded in a six‐well plate (1 × 10 6 cells per well) and treated with different concentrations (2.5, 5, and 10 µM) of ZO.…”

Section: Methodsologymentioning

confidence: 99%

“…The morphological features of nuclear condensation and DNA fragmentation demonstrate apoptosis, which can be detected by Hoechst 33342, nuclear specific staining . HCT116 cells were seeded (1 × 10 6 cells per well) in a six‐well plate treated with different concentrations (2.5, 5, and 10 µM) of ZO for 24 hours.…”

Section: Methodsologymentioning

confidence: 99%

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A ginger derivative, zingerone—a phenolic compound—induces ROS‐mediated apoptosis in colon cancer cells (HCT‐116)

Veeraraghavan

Mohan

et al. 2019

J Biochem & Molecular Tox

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Zingerone (ZO), an active phenolic agent derived from Zingiber officinale (Ginger), has many pharmacological properties such as antioxidant, antiangiogenic, and antitumor. However, its potential value in cancer and the mechanism by which ZO wields its therapeutic effects remain obscure. Therefore, in this current study, we explored the effects of ZO on suppressing cell proliferation and enhancing apoptosis in colon cancer cells (HCT116). Our results indicated that ZO significantly enhances the production of reactive oxygen species, lipid peroxidation (thiobarbituric acid reactive substance [TBARS]), and loss of cell viability; and reduces mitochondrial membrane potential and antioxidant levels (SOD, CAT, and GSH) in ZO‐treated HCT116 cells in a dose‐dependent (2.5, 5, and 10 µM) manner. Furthermore, ZO induces oxidative stress‐mediated apoptosis as evidenced by apoptotic morphological changes predicted by AO/EtBr, Hoechst staining and further confirmed by comet assay. Moreover, immunoblotting techniques showed that ZO treatment effectively enhances Bax, caspase‐9, and caspase‐3 expressions and decreases the expression of Bcl‐2 in colon cancer cells. Together, our results evidenced that the antitumor effects of ZO reduce cell proliferation and stimulate apoptosis through modulating pro‐ and antiapoptotic molecular events in HCT116 colon cancer cells. Therefore, based on our findings, ZO may be used as a therapeutic agent for the treatment of colon cancer.

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Organelle‐Targeted BODIPY Photocages: Visible‐Light‐Mediated Subcellular Photorelease

et al. 2019

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Photocaging facilitates non-invasive and precise spatio-temporal control over the release of biologically relevant small-and macro-molecules using light. However,s ubcellular organelles are dispersed in cells in am anner that renders selective light-irradiation of ac omplete organelle impractical. Organelle-specific photocages could provide ap owerfulm ethod for releasing bioactive molecules in subcellular locations.H erein, we report ag eneral post-synthetic method for the chemical functionalization and further conjugation of meso-methyl BODIPY photocages and the synthesis of endoplasmic reticulum (ER)-, lysosome-, and mitochondria-targeted derivatives.W ea lso demonstrate that 2,4dinitrophenol, am itochondrial uncoupler,a nd puromycin, ap rotein biosynthesis inhibitor,c an be selectively photoreleased in mitochondria and ER, respectively,i nl ive cells by using visible light. Additionally,p hotocaging is shown to lead to higher efficacy of the released molecules,probably owingto alocalized and abrupt release.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.org/10.

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[6]-Shogaol, a dietary phenolic compound, induces oxidative stress mediated mitochondrial dependant apoptosis through activation of proapoptotic factors in Hep-2 cells

Cited by 57 publications

References 53 publications

Promotion of Mitochondrial Biogenesis via Activation of AMPK‐PGC1ɑ Signaling Pathway by Ginger (Zingiber officinale Roscoe) Extract, and Its Major Active Component 6‐Gingerol

Promotion of Mitochondrial Biogenesis via Activation of AMPK‐PGC1ɑ Signaling Pathway by Ginger (Zingiber officinale Roscoe) Extract, and Its Major Active Component 6‐Gingerol

A ginger derivative, zingerone—a phenolic compound—induces ROS‐mediated apoptosis in colon cancer cells (HCT‐116)

Organelle‐Targeted BODIPY Photocages: Visible‐Light‐Mediated Subcellular Photorelease

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