Reversine induces caspase-dependent apoptosis of human osteosarcoma cells through extrinsic and intrinsic apoptotic signaling pathways

Kim, Jae-Sung; Cho, In‐A; Kang, Kyeong‐Rok; Lim, HyangI; Kim, Tae‐Hyeon; Yu, Sun‐Kyoung; Kim, Heung-Joong; Lee, Seul Ah; Moon, Sung Min; Chun, Hong Sung; Kim, Chun Sung; Kim, Do Kyung

doi:10.1007/s13258-019-00790-1

Cited by 20 publications

(16 citation statements)

References 33 publications

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“…Optical density was measured at 570 nm absorbance using an enzyme-linked immunosorbent assay (ELISA) reader (Dynatech Laboratories, Chantilly, VA, USA). The optical density of the formazan crystals formed in untreated control cells was used to represent 100% viability (Kim et al 2019). Data were obtained from three independent experiments.…”

Section: Cell Viability Assaymentioning

confidence: 99%

Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of platycodin D against oxidative stress-induced DNA damage and apoptosis in C2C12 myoblasts

Choi¹

2020

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Myoblast damage by oxidative stress has been proposed as one of the main causes of skeletal muscle loss due to induction of muscle damage. Platycodin D, a triterpenoid saponin found in the root of Platycodon grandiflorum (Jacq.) A. DC., has been known to possess strong antioxidant activity. However, whether platycodin D can defend myoblasts against oxidative injury remains to be elucidated. Therefore, this study was conducted to investigate the potential protective effects of platycodin D against oxidative stress in mouse myoblast C2C12 cells. The results demonstrated that platycodin D inhibited hydrogen peroxide (H 2 O 2)-induced cytotoxicity and DNA damage by blocking abnormal reactive oxygen species (ROS) generation. Furthermore, platycodin D protected cells from the induction of mitochondria-mediated apoptosis by oxidative stress. In addition, platycodin D markedly promoted the activation of nuclear factor-erythroid-2-related factor 2 (Nrf2), which was associated with the enhanced expression of heme oxygenase-1 (HO-1) in the presence of H 2 O 2. However, inhibiting the expression of HO-1 by Nrf2 siRNA significantly attenuated the protective effect of platycodin D, indicating that platycodin D activates the Nrf2/HO-1 signaling pathway to protect against oxidative stress. Based on current data, platycodin D may be useful as a potential therapeutic agent against various oxidative stress-related muscle disorders.

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Section: Cell Viability Assaymentioning

confidence: 99%

Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of platycodin D against oxidative stress-induced DNA damage and apoptosis in C2C12 myoblasts

Choi¹

2020

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“…Cell viability was measured using an MTT assay, as previously described [46]. Hep3B cells were seeded on 96-well plate at a density of 5 × 10 3 cells per well.…”

Section: Cell Viabilitymentioning

confidence: 99%

Induction of Apoptosis by Coptisine in Hep3B Hepatocellular Carcinoma Cells through Activation of the ROS-Mediated JNK Signaling Pathway

Kim

Hwangbo

Lee

et al. 2020

IJMS

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Hepatocellular carcinoma (HCC) has a high mortality rate worldwide, and treatment is very limited due to its high recurrence and low diagnosis rate, and therefore there is an increasing need to develop more effective drugs to treat HCC. Coptisine is one of the isoquinoline alkaloids, and it has various pharmacological effects. However, the evidence for the molecular mechanism of the anticancer efficacy is still insufficient. Therefore, this study investigated the antiproliferative effect of coptisine on human HCC Hep3B cells and identified the action mechanism. Our results showed that coptisine markedly increased DNA damage and apoptotic cell death, which was associated with induction of death receptor proteins. Coptisine also significantly upregulated expression of proapoptotic Bax protein, downregulated expression of anti-apoptotic Bcl-2 protein, and activated caspase-3, -8, and -9. In addition, coptisine remarkably increased the generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential (MMP), and release of cytochrome c into the cytoplasm. However, N-acetylcysteine (NAC), a ROS scavenger, significantly attenuated the apoptosis-inducing effect of coptisine. It is worth noting that coptisine significantly upregulated phosphorylation of ROS-dependent c-Jun N-terminal kinase (JNK), whereas treatment with JNK inhibitor could suppress an apoptosis-related series event. Taken together, our results suggest that coptisine has an anticancer effect in Hep3B cells through ROS-mediated activation of the JNK signaling pathway.

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“…Mitochondria-involved intrinsic apoptosis and death receptor-mediated extrinsic apoptosis frequently engage in crosstalk in the caspase-dependent apoptotic cell death program [38,39]. Our data suggest the involvement of both intrinsic and extrinsic apoptosis pathways in SPS8 action.…”

Section: Discussionmentioning

confidence: 66%

Mechanistic Study of Triazole Based Aminodiol Derivatives in Leukemic Cells—Crosstalk between Mitochondrial Stress-Involved Apoptosis and Autophagy

Chan

Leu

Swain

et al. 2020

IJMS

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Various derivatives that mimic ceramide structures by introducing a triazole to connect the aminodiol moiety and long alkyl chain have been synthesized and screened for their anti-leukemia activity. SPS8 stood out among the derivatives, showing cytotoxic selectivity between leukemic cell lines and human peripheral blood mononuclear cells (about ten times). DAPI nuclear staining and H&E staining revealed DNA fragmentation under the action of SPS8. SPS8 induced an increase in intracellular Ca2+ levels and mitochondrial stress in HL-60 cells identified by the loss of mitochondrial membrane potential, transmission electron microscopy (TEM) examination, and altered expressions of Bcl-2 family proteins. SPS8 also induced autophagy through the detection of Atg5, beclin-1, and LC3 II protein expression, as well as TEM examination. Chloroquine, an autophagy inhibitor, promoted SPS8-induced apoptosis, suggesting the cytoprotective role of autophagy in hindering SPS8 from apoptosis. Furthermore, SPS8 was shown to alter the expressions of a variety of genes using a microarray analysis and volcano plot filtering. A further cellular signaling pathways analysis suggested that SPS8 induced several cellular processes in HL-60, including the sterol biosynthesis process and cholesterol biosynthesis process, and inhibited some cellular pathways, in which STAT3 was the most critical nuclear factor. Further identification revealed that SPS8 inhibited the phosphorylation of STAT3, representing the loss of cytoprotective activity. In conclusion, the data suggest that SPS8 induces both apoptosis and autophagy in leukemic cells, in which autophagy plays a cytoprotective role in impeding apoptosis. Moreover, the inhibition of STAT3 phosphorylation may support SPS8-induced anti-leukemic activity.

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Reversine induces caspase-dependent apoptosis of human osteosarcoma cells through extrinsic and intrinsic apoptotic signaling pathways

Cited by 20 publications

References 33 publications

Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of platycodin D against oxidative stress-induced DNA damage and apoptosis in C2C12 myoblasts

Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of platycodin D against oxidative stress-induced DNA damage and apoptosis in C2C12 myoblasts

Induction of Apoptosis by Coptisine in Hep3B Hepatocellular Carcinoma Cells through Activation of the ROS-Mediated JNK Signaling Pathway

Mechanistic Study of Triazole Based Aminodiol Derivatives in Leukemic Cells—Crosstalk between Mitochondrial Stress-Involved Apoptosis and Autophagy

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