Homoharringtonine mediates myeloid cell apoptosis via upregulation of pro-apoptotic bax and inducing caspase-3-mediated cleavage of poly(ADP-ribose) polymerase (PARP)

American Journal of Hematology
Lou YinjunTong Xiangming

Abstract

Homoharringtonine (HHT) is a plant alkaloid with antileukemia activity that is currently being used for treatment of acute, chronic leukemias and MDS. In this study, we show that HHT can induce apoptosis in a variety of human myeloid leukemia cell lines (U937, HL-60, HEL, THP, and K562). U937 and HL60 cells undergo rapid apoptosis on treatment with HHT, as indicated by increased annexin V binding capacity, caspase-3 activation, and cleavage of poly(ADP-ribose) polymerase (PARP). In addition, the expression of bax is upregulated during HHT-induced cell death, whereas the expression of bcl-2 is only slightly decreased. Importantly, treatment of primary leukemic cells, obtained from acute myeloid leukemia patients, resulted in rapid apoptosis. Thus, our data provide the mechanism of HHT and justify the use of HHT in the treatment of human myeloid leukemia.

References

May 1, 1985·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·R P WarrellT S Gee
Jan 1, 1993·Cancer Chemotherapy and Pharmacology·L J WilkoffJ P Donahue
Sep 12, 1998·Science·J M Adams, S Cory
Dec 18, 2001·Cancer·H M KantarjianS M O'Brien

❮ Previous
Next ❯

Citations

May 18, 2007·Acta Pharmacologica Sinica·Wei JinZhi-Min Shao
Jan 7, 2014·Journal of Hematology & Oncology·Shuqing Lü, Jianmin Wang
Jul 7, 2007·Leukemia & Lymphoma·Yin-Jun LouJie Jin
Jul 24, 2013·Expert Opinion on Pharmacotherapy·Aziz NazhaAlfonso Quintás-Cardama
Mar 1, 2007·Expert Opinion on Drug Discovery·Nadine DarwicheHala Gali-Muhtasib
Apr 2, 2008·Expert Opinion on Pharmacotherapy·Alfonso Quintás-Cardama, Jorge Cortes
Oct 9, 2015·British Journal of Pharmacology·Ting ZhangJie Jin
Dec 17, 2014·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Akihiro WatariMasuo Kondoh
Feb 19, 2010·Expert Opinion on Pharmacotherapy·Mohamed Amine ZaoualiJoan Roselló-Catafau
Jan 15, 2013·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·F S Lizarte NetoL F Tirapelli
Sep 10, 2009·Cancer·Alfonso Quintás-CardamaJorge Cortes
Jan 25, 2006·American Journal of Hematology·Jia-Jun LiuFeng Chen
Oct 16, 2019·Oncology Letters·Zixiang WangJicai Chen
May 16, 2018·International Journal of Molecular Sciences·Jianjian ZhuangHongdong Li
Jun 1, 2018·Oncology and Therapy·Eric S Winer, Daniel J DeAngelo
Jul 25, 2021·Clinical Lymphoma, Myeloma & Leukemia·Ruihua MiXudong Wei

❮ Previous
Next ❯

Related Concepts

Related Feeds

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

B-Cell Leukemia (Keystone)

B-cell leukemia includes various types of lymphoid leukemia that affect B cells. Here is the latest research on B-cell leukemia.

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

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