Cardiotoxin III induces c‐jun N‐terminal kinase‐dependent apoptosis in HL‐60 human leukaemia cells

Chien, Ching-Ming; Yang, Sheng-Huei; Yang, Chun-Chieh; Chang, Long‐Sen; Lin, Shinne‐Ren

doi:10.1002/cbf.1420

Cited by 17 publications

(5 citation statements)

References 25 publications

(32 reference statements)

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“…To further confirm apoptosis in 4βHWE-induced H1299 cells, annexin V and PI double-staining (Pharmingen, San Diego, CA) was performed as described before [30]. In brief, 1 × 10 6 cells per 100-mm Petri-dish (at 70%~80% confluency) were treated with vehicle or 51 μg/mL of 4βHWE for 24 h. Subsequently, cells were labeled with annexin V-FITC (10 μg/mL)/PI (10 μg/mL); stained slides were mounted, and analyzed using an inverted fluorescence microscope (TE2000-U; Nikon).…”

Section: Methodsmentioning

confidence: 99%

4β-Hydroxywithanolide E from Physalis peruviana (golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest

et al. 2010

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BackgroundThe crude extract of the fruit bearing plant, Physalis peruviana (golden berry), demonstrated anti-hepatoma and anti-inflammatory activities. However, the cellular mechanism involved in this process is still unknown.MethodsHerein, we isolated the main pure compound, 4β-Hydroxywithanolide (4βHWE) derived from golden berries, and investigated its antiproliferative effect on a human lung cancer cell line (H1299) using survival, cell cycle, and apoptosis analyses. An alkaline comet-nuclear extract (NE) assay was used to evaluate the DNA damage due to the drug.ResultsIt was shown that DNA damage was significantly induced by 1, 5, and 10 μg/mL 4βHWE for 2 h in a dose-dependent manner (p < 0.005). A trypan blue exclusion assay showed that the proliferation of cells was inhibited by 4βHWE in both dose- and time-dependent manners (p < 0.05 and 0.001 for 24 and 48 h, respectively). The half maximal inhibitory concentrations (IC50) of 4βHWE in H1299 cells for 24 and 48 h were 0.6 and 0.71 μg/mL, respectively, suggesting it could be a potential therapeutic agent against lung cancer. In a flow cytometric analysis, 4βHWE produced cell cycle perturbation in the form of sub-G1 accumulation and slight arrest at the G2/M phase with 1 μg/mL for 12 and 24 h, respectively. Using flow cytometric and annexin V/propidium iodide immunofluorescence double-staining techniques, these phenomena were proven to be apoptosis and complete G2/M arrest for H1299 cells treated with 5 μg/mL for 24 h.ConclusionsIn this study, we demonstrated that golden berry-derived 4βHWE is a potential DNA-damaging and chemotherapeutic agent against lung cancer.

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Section: Methodsmentioning

confidence: 99%

4β-Hydroxywithanolide E from Physalis peruviana (golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest

et al. 2010

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“…(PharMingen, San Diego, CA) was used as described (Chien et al, 2008). In brief, cells were treated with vehicle or 3.57 mM of protoapigenone in medium for 24 h. After exposure, the cells were labeled with Annexin V conjugated fluorescein isothiocyanate (Annexin V-FITC) (10 mg=mL) and PI (10 mg=mL).…”

Section: Lung Cancer Cell Killing By Protoapigenone 503mentioning

confidence: 99%

Fern Plant–Derived Protoapigenone Leads to DNA Damage, Apoptosis, and G₂/M Arrest in Lung Cancer Cell Line H1299

Chiu

Chang

Chuang

et al. 2009

DNA and Cell Biology

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Protoapigenone, isolated from the native fern plant Thelypteris torresiana, has anticancer activity against some cancer cells. However, the toxicological mechanism for protoapigenone is still unknown. Here, we investigated the anticancer effect of protoapigenone on human lung cancer cell lines. The comet assay showed that DNA damage induced by protoapigenone is dose-dependent. Trypan blue exclusion showed that the cell killing by protoapigenone is both time and dose dependent. The IC(50) of protoapigenone for 12, 24, and 48 h in H1299 cells is 6.11, 2.74, and 1.49 microM, respectively. Flow cytometry showed cell cycle perturbation such as sub-G(1) accumulation (at 1.57 microM for 48 h and at 3.57 microM for 12 and 24 h) and G(2)/M arrest (at 3.57 microM for 12 and 24 h) for protoapigenone. The sub-G(1) accumulation phenomena in the 3.57 microM for 24 h sample were shown to be apoptosis using Annexin V-immunofluorescence/propidium iodide staining. These results suggest protoapigenone is a potential chemotherapeutic agent for lung cancers.

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“…Cobra cardiotoxins (CTXs) show a wide range of biological activities including hemolysis, cardiotoxicity, and disruption of muscular integrity [1,2,3]. Moreover, accumulated evidence has shown that CTXs induce apoptosis in cancer cells through the mitochondria-mediated apoptotic pathway, lysosome-mediated death pathway, or membrane-damaging effects [4,5,6,7,8]. It is widely believed that the plasma membrane is a target of CTXs, but the membrane pore formed by CTXs may have a limited lifetime on the cell surface due to membrane reorganization [9].…”

Section: Introductionmentioning

confidence: 99%

Naja atra Cardiotoxin 3 Elicits Autophagy and Apoptosis in U937 Human Leukemia Cells through the Ca2+/PP2A/AMPK Axis

Chiou

Shi

Wang

et al. 2019

Toxins

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Cardiotoxins (CTXs) are suggested to exert their cytotoxicity through cell membrane damage. Other studies show that penetration of CTXs into cells elicits mitochondrial fragmentation or lysosome disruption, leading to cell death. Considering the role of AMPK-activated protein kinase (AMPK) in mitochondrial biogenesis and lysosomal biogenesis, we aimed to investigate whether the AMPK-mediated pathway modulated Naja atra (Taiwan cobra) CTX3 cytotoxicity in U937 human leukemia cells. Our results showed that CTX3 induced autophagy and apoptosis in U937 cells, whereas autophagic inhibitors suppressed CTX3-induced apoptosis. CTX3 treatment elicited Ca2+-dependent degradation of the protein phosphatase 2A (PP2A) catalytic subunit (PP2Acα) and phosphorylation of AMPKα. Overexpression of PP2Acα mitigated the CTX3-induced AMPKα phosphorylation. CTX3-induced autophagy was via AMPK-mediated suppression of the Akt/mTOR pathway. Removal of Ca2+ or suppression of AMPKα phosphorylation inhibited the CTX3-induced cell death. CTX3 was unable to induce autophagy and apoptosis in U937 cells expressing constitutively active Akt. Met-modified CTX3 retained its membrane-perturbing activity, however, it did not induce AMPK activation and death of U937 cells. These results conclusively indicate that CTX3 induces autophagy and apoptosis in U937 cells via the Ca2+/PP2A/AMPK axis, and suggest that the membrane-perturbing activity of CTX3 is not crucial for the cell death signaling pathway induction.

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Cardiotoxin III induces c‐jun N‐terminal kinase‐dependent apoptosis in HL‐60 human leukaemia cells

Cited by 17 publications

References 25 publications

4β-Hydroxywithanolide E from Physalis peruviana (golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest

4β-Hydroxywithanolide E from Physalis peruviana (golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest

Fern Plant–Derived Protoapigenone Leads to DNA Damage, Apoptosis, and G₂/M Arrest in Lung Cancer Cell Line H1299

Naja atra Cardiotoxin 3 Elicits Autophagy and Apoptosis in U937 Human Leukemia Cells through the Ca2+/PP2A/AMPK Axis

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Cardiotoxin III induces c‐jun N‐terminal kinase‐dependent apoptosis in HL‐60 human leukaemia cells

Cited by 17 publications

References 25 publications

4β-Hydroxywithanolide E from Physalis peruviana (golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest

4β-Hydroxywithanolide E from Physalis peruviana (golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest

Fern Plant–Derived Protoapigenone Leads to DNA Damage, Apoptosis, and G2/M Arrest in Lung Cancer Cell Line H1299

Naja atra Cardiotoxin 3 Elicits Autophagy and Apoptosis in U937 Human Leukemia Cells through the Ca2+/PP2A/AMPK Axis

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Fern Plant–Derived Protoapigenone Leads to DNA Damage, Apoptosis, and G₂/M Arrest in Lung Cancer Cell Line H1299