HDAC1,2 Knock-Out and HDACi Induced Cell Apoptosis in Imatinib-Resistant K562 Cells

International Journal of Molecular Sciences
Shu-Huey ChenChia-Hwa Lee

Abstract

Since imatinib (Glivec or Gleevec) has been used to target the BCR-ABL fusion protein, chronic myeloid leukemia (CML) has become a manageable chronic disease with long-term survival. However, 15%-20% of CML patients ultimately develop resistance to imatinib and then progress to an accelerated phase and eventually to a blast crisis, limiting treatment options and resulting in a poor survival rate. Thus, we investigated whether histone deacetylase inhibitors (HDACis) could be used as a potential anticancer therapy for imatinib-resistant CML (IR-CML) patients. By applying a noninvasive apoptosis detection sensor (NIADS), we found that panobinostat significantly enhanced cell apoptosis in K562 cells. A further investigation showed that panobinostat induced apoptosis in both K562 and imatinib-resistant K562 (IR-K562) cells mainly via H3 and H4 histone acetylation, whereas panobinostat targeted cancer stem cells (CSCs) in IR-K562 cells. Using CRISPR/Cas9 genomic editing, we found that HDAC1 and HDAC2 knockout cells significantly induced cell apoptosis, indicating that the regulation of HDAC1 and HDAC2 is extremely important in maintaining K562 cell survival. All information in this study indicates that regulating HDAC activity provid...Continue Reading

References

Jan 22, 2004·Proceedings of the National Academy of Sciences of the United States of America·C-Y GuiP A Marks
Aug 25, 2010·Journal of the National Cancer Institute·Chia-Hwa LeeYuan-Soon Ho
Mar 8, 2013·Cellular and Molecular Life Sciences : CMLS·Claudia Cosentino, Raul Mostoslavsky
Aug 10, 2013·Mutation Research·Fade Gong, Kyle M Miller
Dec 18, 2013·Science·Ophir ShalemFeng Zhang
Aug 20, 2015·International Journal of Molecular Sciences·Veronika Borutinskaitė, Rūta Navakauskienė
Sep 1, 2016·Journal of Cancer Research and Clinical Oncology·Nisintha MahendrarajahOliver H Krämer
Dec 17, 2016·Molecular Cancer Therapeutics·Noël J-M RaynalJean-Pierre J Issa
Jan 31, 2017·International Journal of Molecular Sciences·Yun ChenSheng-Hong Tseng
Apr 19, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Xia LiJie Jin
Jun 3, 2017·Clinical Epigenetics·Roberta MazzoneSergio Valente
Jul 4, 2017·International Journal of Molecular Sciences·Tomas EckschlagerJan Hrabeta
Aug 23, 2017·International Journal of Molecular Sciences·Naofumi MukaidaTomohisa Baba
Jun 16, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Hélène MarijonH Phillip Koeffler
Oct 12, 2018·International Journal of Molecular Sciences·Johanna S Ungerstedt
Nov 20, 2018·Surgical Oncology·Diamantis I TsilimigrasTimothy M Pawlik
Jan 24, 2019·International Journal of Molecular Sciences·Ching-Ling LinChia-Hwa Lee

❮ Previous
Next ❯

Citations

Mar 30, 2021·Molecular Pharmaceutics·Pratheppa RajagopalUma Maheswari Krishnan
Jun 15, 2021·Journal of Analytical Methods in Chemistry·Sijiang Liu, Zhaojin Yu

❮ Previous
Next ❯

Methods Mentioned

BETA
acetylation
transfection
flow cytometry
Histone Acetylation
gene knockout
PCR
Polymerase Chain Reaction
electrophoresis

Software Mentioned

SigmaPlot
NIADS
Roche LightCycler
Statistical Package for the Social Sciences
Living Image

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.