Cantharidic acid induces apoptosis of human leukemic HL-60 cells via c-Jun N-terminal kinase-regulated caspase-8/-9/-3 activation pathway

Shih Chung Wang, Jyh Ming Chow, Ming Hsien Chien, Chiao Wen Lin, Hui Yu Chen, Pei Ching Hsiao, Shun Fa Yang

研究成果: 雜誌貢獻文章

7 引文 (Scopus)

摘要

Cantharidin, a natural toxin from blister beetles, has shown potent anticancer activities on many solid tumor cells. Recently, cantharidin and its analogue, norcantharidin, were also shown to suppress nonsolid tumors such as chronic myeloid leukemia, acute myeloid leukemia (AML), and leukemic stem cells. However, there is no available information to address the effects of cantharidic acid (CAC), a hydrolysis product of cantharidin, on human AML cells. The present study showed that CAC, at a range of concentrations (0-20 μM), concentration-dependently inhibited cell proliferation in the HL-60 AML cell line. Western blot and flow cytometric assays demonstrated that CAC induced several features of apoptosis such as sub G1-phase cell increase, phosphatidylserine (PS) externalization, and significantly activated proapoptotic signaling including caspase-8, -9, and -3 activation and poly(ADP-ribose) polymerase (PARP) cleavage in HL-60 AML cells. Moreover, treatment of HL-60 cells with CAC induced concentration- and time- dependent activation of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK). Only JNK-, but not p38 MAPK-specific inhibitor can reverse the CAC-induced activation of the caspase-8, -9, and -3. We concluded that CAC can induce apoptosis in human leukemic HL-60 cells via a caspases-dependent pathway, and that the apoptosis-inducing effect of CAC can be regulated by JNK activation signaling.

原文英語
期刊Environmental Toxicology
DOIs
出版狀態接受/付印 - 一月 1 2018

指紋

Caspase 9
Caspase 8
JNK Mitogen-Activated Protein Kinases
HL-60 Cells
apoptosis
Chemical activation
Apoptosis
Cantharidin
Acids
acid
Acute Myeloid Leukemia
Myeloid Cells
norcantharidin
p38 Mitogen-Activated Protein Kinases
tumor
Tumors
Phosphotransferases
Cells
protein
Poly(ADP-ribose) Polymerases

ASJC Scopus subject areas

  • Toxicology
  • Management, Monitoring, Policy and Law
  • Health, Toxicology and Mutagenesis

引用此文

Cantharidic acid induces apoptosis of human leukemic HL-60 cells via c-Jun N-terminal kinase-regulated caspase-8/-9/-3 activation pathway. / Wang, Shih Chung; Chow, Jyh Ming; Chien, Ming Hsien; Lin, Chiao Wen; Chen, Hui Yu; Hsiao, Pei Ching; Yang, Shun Fa.

於: Environmental Toxicology, 01.01.2018.

研究成果: 雜誌貢獻文章

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title = "Cantharidic acid induces apoptosis of human leukemic HL-60 cells via c-Jun N-terminal kinase-regulated caspase-8/-9/-3 activation pathway",
abstract = "Cantharidin, a natural toxin from blister beetles, has shown potent anticancer activities on many solid tumor cells. Recently, cantharidin and its analogue, norcantharidin, were also shown to suppress nonsolid tumors such as chronic myeloid leukemia, acute myeloid leukemia (AML), and leukemic stem cells. However, there is no available information to address the effects of cantharidic acid (CAC), a hydrolysis product of cantharidin, on human AML cells. The present study showed that CAC, at a range of concentrations (0-20 μM), concentration-dependently inhibited cell proliferation in the HL-60 AML cell line. Western blot and flow cytometric assays demonstrated that CAC induced several features of apoptosis such as sub G1-phase cell increase, phosphatidylserine (PS) externalization, and significantly activated proapoptotic signaling including caspase-8, -9, and -3 activation and poly(ADP-ribose) polymerase (PARP) cleavage in HL-60 AML cells. Moreover, treatment of HL-60 cells with CAC induced concentration- and time- dependent activation of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK). Only JNK-, but not p38 MAPK-specific inhibitor can reverse the CAC-induced activation of the caspase-8, -9, and -3. We concluded that CAC can induce apoptosis in human leukemic HL-60 cells via a caspases-dependent pathway, and that the apoptosis-inducing effect of CAC can be regulated by JNK activation signaling.",
keywords = "Acute myeloid leukemia, Apoptosis, C-Jun N-terminal kinase, Cantharidic acid",
author = "Wang, {Shih Chung} and Chow, {Jyh Ming} and Chien, {Ming Hsien} and Lin, {Chiao Wen} and Chen, {Hui Yu} and Hsiao, {Pei Ching} and Yang, {Shun Fa}",
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AU - Wang, Shih Chung

AU - Chow, Jyh Ming

AU - Chien, Ming Hsien

AU - Lin, Chiao Wen

AU - Chen, Hui Yu

AU - Hsiao, Pei Ching

AU - Yang, Shun Fa

PY - 2018/1/1

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N2 - Cantharidin, a natural toxin from blister beetles, has shown potent anticancer activities on many solid tumor cells. Recently, cantharidin and its analogue, norcantharidin, were also shown to suppress nonsolid tumors such as chronic myeloid leukemia, acute myeloid leukemia (AML), and leukemic stem cells. However, there is no available information to address the effects of cantharidic acid (CAC), a hydrolysis product of cantharidin, on human AML cells. The present study showed that CAC, at a range of concentrations (0-20 μM), concentration-dependently inhibited cell proliferation in the HL-60 AML cell line. Western blot and flow cytometric assays demonstrated that CAC induced several features of apoptosis such as sub G1-phase cell increase, phosphatidylserine (PS) externalization, and significantly activated proapoptotic signaling including caspase-8, -9, and -3 activation and poly(ADP-ribose) polymerase (PARP) cleavage in HL-60 AML cells. Moreover, treatment of HL-60 cells with CAC induced concentration- and time- dependent activation of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK). Only JNK-, but not p38 MAPK-specific inhibitor can reverse the CAC-induced activation of the caspase-8, -9, and -3. We concluded that CAC can induce apoptosis in human leukemic HL-60 cells via a caspases-dependent pathway, and that the apoptosis-inducing effect of CAC can be regulated by JNK activation signaling.

AB - Cantharidin, a natural toxin from blister beetles, has shown potent anticancer activities on many solid tumor cells. Recently, cantharidin and its analogue, norcantharidin, were also shown to suppress nonsolid tumors such as chronic myeloid leukemia, acute myeloid leukemia (AML), and leukemic stem cells. However, there is no available information to address the effects of cantharidic acid (CAC), a hydrolysis product of cantharidin, on human AML cells. The present study showed that CAC, at a range of concentrations (0-20 μM), concentration-dependently inhibited cell proliferation in the HL-60 AML cell line. Western blot and flow cytometric assays demonstrated that CAC induced several features of apoptosis such as sub G1-phase cell increase, phosphatidylserine (PS) externalization, and significantly activated proapoptotic signaling including caspase-8, -9, and -3 activation and poly(ADP-ribose) polymerase (PARP) cleavage in HL-60 AML cells. Moreover, treatment of HL-60 cells with CAC induced concentration- and time- dependent activation of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK). Only JNK-, but not p38 MAPK-specific inhibitor can reverse the CAC-induced activation of the caspase-8, -9, and -3. We concluded that CAC can induce apoptosis in human leukemic HL-60 cells via a caspases-dependent pathway, and that the apoptosis-inducing effect of CAC can be regulated by JNK activation signaling.

KW - Acute myeloid leukemia

KW - Apoptosis

KW - C-Jun N-terminal kinase

KW - Cantharidic acid

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