ZT-25, a new vacuolar H+-ATPase inhibitor, induces apoptosis and protective autophagy through ROS generation in HepG2 cells

Lu, Yapeng; Zhang, Rui; Liu, Siyuan; Zhao, Yu; Gao, Jing; Zhu, Li

doi:10.1016/j.ejphar.2015.12.026

Cited by 45 publications

(34 citation statements)

References 54 publications

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“…KH-0005; Key Organics) in 100 µl DMSO and 900 µl RPMI-1640 medium (supplemented with 10% FBS and 1% penicillin streptomycin). The solution was then sterilized using a 0.22-µm filter and stored at 4˚C and diluted to 10 µM as previously described (21)(22)(23)(24).…”

Section: Methodsmentioning

confidence: 99%

Hydroxysafflor yellow�A induces autophagy in human liver cancer cells by regulating Beclin�1 and ERK expression

Chen

Liu

et al. 2020

Exp Ther Med

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Hydroxysafflor yellow A (HSYA) is a water-soluble component of the safflower (Carthamus tinctorius), and research has revealed that HSYA exhibits antitumor effects. In the present study, the effects of HSYA on the autophagy of a Hep-G2 liver cancer cell line, as well as the underlying mechanisms, were investigated. Hep-G2 cells were treated with HSYA and the viability of cells was measured using an MTT assay. Western blotting and immunofluorescence assays were performed to determine the expression of light chain 3 II (LC3-II) and p62, as well as the autophagy regulators Beclin 1 and ERK1/2. Transmission electron microscopy was performed to observe the formation of autophagosomes. The combined effects of HSYA and the autophagy inhibitor chloroquine (CQ) were also determined. The results revealed that the viability of Hep-G2 cells decreased with increasing concentrations of HSYA. Furthermore, LC3-II expression increased significantly and the level of p62 decreased significantly in the HYSA group compared with the control group. Additionally, an increase in Beclin 1 expression and a decrease in phosphorylated-ERK1/2 expression was observed in Hep-G2 cells treated with HYSA. Following treatment with CQ and HSYA, a significant increase in the viability of Hep-G2 cells was observed compared with the HSYA group. Collectively, the results indicated that HSYA induced autophagy by promoting the expression of Beclin 1 and inhibiting the phosphorylation of ERK in liver cancer cells. Therefore, HSYA may serve as a potential therapeutic agent for liver cancer.

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Section: Methodsmentioning

confidence: 99%

Hydroxysafflor yellow�A induces autophagy in human liver cancer cells by regulating Beclin�1 and ERK expression

Chen

Liu

et al. 2020

Exp Ther Med

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“…Cells were incubated with 50 µM DCFH‐DA (Sigma) for 30 minutes at 37°C in a dark place. After washing with phosphate buffer solution, the fluorescence intensity was measured as previously described …”

Section: Methodsmentioning

confidence: 99%

“…After washing with phosphate buffer solution, the fluorescence intensity was measured as previously described. 19…”

Section: Measurement Of Reactive Oxygen Speciesmentioning

confidence: 99%

miR‐200a mediates protection of thymosin β‐4 in cardiac microvascular endothelial cells as a novel mechanism under hypoxia‐reoxygenation injury

Zhu

Liu

et al. 2019

J of Cellular Biochemistry

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Thymosin β‐4 (Tβ4) is a ubiquitous protein, which has been suggested to regulate multiple cell signal pathways and a variety of cellular functions. However, the role Tβ4 plays in the cardiac microvascular endothelial cells (CMECs) under myocardial ischemia/reperfusion injury is currently unknown. Here we investigated the effects of Tβ4 on hypoxia/reoxygenation (H/R) induced CMECs injury and its potential molecular mechanism. Cultured CMECs were positively identified by flow cytometry using antibody against CD31 and VWF/Factor VIII, which are constitutively expressed on the surface of CMECs. Then the reduced level of Tβ4 was detected in H/R‐CMECs by a real‐time quantitative polymerase chain reaction. To determine the effects of Tβ4 on H/R‐CMECs, we transfected the overexpression or silence vector of Tβ4 into CMECs under H/R condition. Our results indicated that H/R treatment could reduce proliferation, increased apoptosis, adhesion, and reactive oxygen species (ROS) production in CMECs, which were attenuated by Tβ4 overexpression or aggravated by Tβ4 silencing, implying Tβ4 is able to promote CMECs against H/R‐induced cell injury. Furthermore, the microRNA‐200a (miR‐200a) level was also increased by Tβ4 in H/R‐CMECs or reduced by Tβ4 small interfering RNA. To investigated the mechanism of protective effects of Tβ4 on CMECs injury, the miR‐200a inhibitor was transfected into H/R‐CMECs. The results indicated that inhibition of miR‐200a inversed the protection of Tβ4 on H/R‐CMECs, specifically including cell proliferation, cell adhesion, cell apoptosis, and ROS production, as well as nuclear factor erythroid 2‐related factor 2 (Nrf2) nuclear translocation. In conclusion, our results determined that Tβ4 attenuated H/R‐induced CMECs injury by miR‐200a‐Nrf2 signaling.

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“…However, prolonged treatment with low concentrations of V-ATPase inhibitors eventually results in apoptosis. Cell death occurs more rapidly when tumor cells are treated with a combination of V-ATPase and autophagy inhibitors (109,174).…”

Section: B V-atpases and Autophagymentioning

confidence: 99%

The Function of V-ATPases in Cancer

Stransky

Cotter

Forgac

2016

Physiological Reviews

234

268

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The vacuolar ATPases (V-ATPases) are a family of proton pumps that couple ATP hydrolysis to proton transport into intracellular compartments and across the plasma membrane. They function in a wide array of normal cellular processes, including membrane traffic, protein processing and degradation, and the coupled transport of small molecules, as well as such physiological processes as urinary acidification and bone resorption. The V-ATPases have also been implicated in a number of disease processes, including viral infection, renal disease, and bone resorption defects. This review is focused on the growing evidence for the important role of V-ATPases in cancer. This includes functions in cellular signaling (particularly Wnt, Notch, and mTOR signaling), cancer cell survival in the highly acidic environment of tumors, aiding the development of drug resistance, as well as crucial roles in tumor cell invasion, migration, and metastasis. Of greatest excitement is evidence that at least some tumors express isoforms of V-ATPase subunits whose disruption is not lethal, leading to the possibility of developing anti-cancer therapeutics that selectively target V-ATPases that function in cancer cells.

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ZT-25, a new vacuolar H+-ATPase inhibitor, induces apoptosis and protective autophagy through ROS generation in HepG2 cells

Cited by 45 publications

References 54 publications

Hydroxysafflor yellow�A induces autophagy in human liver cancer cells by regulating Beclin�1 and ERK expression

Hydroxysafflor yellow�A induces autophagy in human liver cancer cells by regulating Beclin�1 and ERK expression

miR‐200a mediates protection of thymosin β‐4 in cardiac microvascular endothelial cells as a novel mechanism under hypoxia‐reoxygenation injury

The Function of V-ATPases in Cancer

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