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

Cantharidic acid induces apoptosis of human leukemic HL‐60 cells via c‐Jun N‐terminal... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Environmental Toxicology Wiley

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

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Publisher
Wiley Subscription Services, Inc., A Wiley Company
Copyright
© 2018 Wiley Periodicals, Inc.
ISSN
1520-4081
eISSN
1522-7278
D.O.I.
10.1002/tox.22537
Publisher site
See Article on Publisher Site

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.

Journal

Environmental ToxicologyWiley

Published: Jan 1, 2018

Keywords: ; ; ;

References

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