Saururus chinensis Baill induces apoptosis through endoplasmic reticulum stress in HepG2 hepatocellular carcinoma cells

Lee, Ah Young; Han, Young-Ah; Kim, Ji‐Eun; Hong, Sun; Park, Eun-Jung; Cho, Myung‐Haing

doi:10.1016/j.fct.2015.05.008

Cited by 14 publications

(4 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, the influx of Ca 2+ to the mitochondria activates the release of cytochrome c along with the mitochondrial pathway related to activation of downstream caspases, especially caspase-3. Furthermore, caspase-3 is necessary for PARP cleavage, an important marker of apoptosis [44].…”

Section: Herbal Extractsmentioning

confidence: 99%

Natural Products Targeting ER Stress, and the Functional Link to Mitochondria

Martucciello

Masullo

Cerulli

et al. 2020

IJMS

View full text Add to dashboard Cite

The endoplasmic reticulum (ER) is a dynamic organelle essential for intracellular homeostasis maintenance, controlling synthesis, the folding of secreted and membrane-bound proteins, and transport of Ca2+. During cellular stress, ER dysfunction leads to the activation of unfolded protein response (UPR) due to accumulated misfolded proteins in the ER. This condition is referred as ER stress. Mitochondria and ER form a site of close contact (the mitochondria-associated membrane, MAM) which is a major platform exerting important physiological roles in the regulation of intracellular Ca2+ homeostasis, lipid metabolism, mitochondrial fission, autophagosome formation, and apoptosis progression. Natural products have been receiving increasing attention for their ability to interfere with ER stress. Research works have focused on the capacity of these bioactive compounds to induce apoptosis by activating ER stress through the ER stress-mediated mitochondrial apoptotic pathway. In this review we discuss the role of natural products in the signaling communication between ER and mitochondria, focusing on the effects induced by ER stress including Ca2+ permeability transition and UPR signaling (protein kinase R-like ER kinase/mitofusin 2).

show abstract

Section: Herbal Extractsmentioning

confidence: 99%

Natural Products Targeting ER Stress, and the Functional Link to Mitochondria

Martucciello

Masullo

Cerulli

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…We have also found a greater level of intracellular Ca ++ influx in the exposed cells. An elevated level of intracellular Ca ++ influx has the ability to either directly activate caspases or cause Ca ++ flux in mitochondria [ 71 ]. Our data on ROS, MMP, and Ca ++ flux are in close agreement with a previous report affirming oxidative stress, mitochondrial dysfunction, and Ca ++ flux in SH-SY5Y cells after TDCPP exposure [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Organophosphorus Flame Retardant TDCPP Displays Genotoxic and Carcinogenic Risks in Human Liver Cells

Saquib

Alsalem

Siddiqui

et al. 2022

Cells

View full text Add to dashboard Cite

Tris(1,3-Dichloro-2-propyl)phosphate (TDCPP) is an organophosphorus flame retardant (OPFR) widely used in a variety of consumer products (plastics, furniture, paints, foams, and electronics). Scientific evidence has affirmed the toxicological effects of TDCPP in in vitro and in vivo test models; however, its genotoxicity and carcinogenic effects in human cells are still obscure. Herein, we present genotoxic and carcinogenic properties of TDCPP in human liver cells (HepG2). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and neutral red uptake (NRU) assays demonstrated survival reduction in HepG2 cells after 3 days of exposure at higher concentrations (100–400 μM) of TDCPP. Comet assay and flow cytometric cell cycle experiments showed DNA damage and apoptosis in HepG2 cells after 3 days of TDCPP exposure. TDCPP treatment incremented the intracellular reactive oxygen species (ROS), nitric oxide (NO), Ca2+ influx, and esterase level in exposed cells. HepG2 mitochondrial membrane potential (ΔΨm) significantly declined and cytoplasmic localization of P53, caspase 3, and caspase 9 increased after TDCPP exposure. qPCR array quantification of the human cancer pathway revealed the upregulation of 11 genes and downregulation of two genes in TDCPP-exposed HepG2 cells. Overall, this is the first study to explicitly validate the fact that TDCPP bears the genotoxic, hepatotoxic, and carcinogenic potential, which may jeopardize human health.

show abstract

“…It appeared that CHOP upregulation was triggered by ROS generation and Ca 2+ increase, because antioxidants (NAC and catalase) and BAPTA-AM were able to block TSN-induced CHOP expression. Evidence revealed that ER stress could lead to Ca 2+ release from the ER to the cytosol 30 . Consistent with these results, we found that TSN-triggered Ca 2+ increase was largely attenuated in cells transfected with PERK siRNA.…”

Section: Discussionmentioning

confidence: 99%

“…Transmission electron microscopy (TEM) was performed to capture autophagic vacuoles following the conventional protocols described previously 30 . For cell treatment, A549 cells were grown in 10-cm dishes to 70% confluence and treated with or without TRAIL or TSN as indicated for 8 hours, and then cells were collected and washed with ice-cold PBS.…”

Section: Methodsmentioning

confidence: 99%

Reversal of the Apoptotic Resistance of Non-Small-Cell Lung Carcinoma towards TRAIL by Natural Product Toosendanin

You

Liu

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively triggers cancer cell death via its association with death receptors on the cell membrane, but exerts negligible side effects on normal cells. However, some non-small-cell lung carcinoma (NSCLC) patients exhibited resistance to TRAIL treatment in clinical trials, and the mechanism varies. In this study, we described for the first time that toosendanin (TSN), a triterpenoid derivative used in Chinese medicine for pain management, could significantly sensitize human primary NSCLC cells or NSCLC cell lines to TRAIL-mediated apoptosis both in vitro and in vivo, while showing low toxicity against human primary cells or tissues. The underlying apoptotic mechanisms involved upregulation of death receptor 5 (DR5) and CCAAT/enhancer binding protein homologous protein, which is related to the endoplasmic reticulum stress response, and is further associated with reactive oxygen species generation and Ca2+ accumulation. Surprisingly, TSN also induced autophagy in NSCLC cells, which recruited membrane DR5, and subsequently antagonized the apoptosis-sensitizing effect of TSN. Taken together, TSN can be used to sensitize tumors and the combination of TRAIL and TSN may represent a useful strategy for NSCLC therapy; moreover, autophagy serves as an important drug resistance mechanism for TSN.

show abstract

Saururus chinensis Baill induces apoptosis through endoplasmic reticulum stress in HepG2 hepatocellular carcinoma cells

Cited by 14 publications

References 36 publications

Natural Products Targeting ER Stress, and the Functional Link to Mitochondria

Natural Products Targeting ER Stress, and the Functional Link to Mitochondria

Organophosphorus Flame Retardant TDCPP Displays Genotoxic and Carcinogenic Risks in Human Liver Cells

Reversal of the Apoptotic Resistance of Non-Small-Cell Lung Carcinoma towards TRAIL by Natural Product Toosendanin

Contact Info

Product

Resources

About