Hexahydro-β-acids induce apoptosis through mitochondrial pathway, GADD153 expression, and caspase activation in human leukemia cells

2011 ◽  
Vol 49 (4) ◽  
pp. 1033-1042 ◽  
Author(s):  
Cheng Bin Liu ◽  
Li-Hua Chen ◽  
An-Chin Cheng ◽  
Wei-Jen Chen ◽  
Mei-Ling Tsai ◽  
...  
Keyword(s):  
Mitochondrial Pathway ◽  
Leukemia Cells ◽  
Human Leukemia ◽  
Caspase Activation ◽  
Human Leukemia Cells ◽  
Gadd153 Expression

Magnolol induces apoptosis in human leukemia cells via cytochrome c release and caspase activation

2003 ◽  
Vol 14 (3) ◽  
pp. 211-217 ◽  
Author(s):  
Wen-Bin Zhong ◽  
Chih-Yuan Wang ◽  
Kuo-Jang Ho ◽  
Fung-Jou Lu ◽  
Tien-Chun Chang ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Leukemia Cells ◽  
Human Leukemia ◽  
Caspase Activation ◽  
Cytochrome C Release ◽  
Human Leukemia Cells

scholarly journals Synergistic antileukemic interactions between 2-medroxyestradiol (2-ME) and histone deacetylase inhibitors involve Akt down-regulation and oxidative stress

Blood ◽  
2006 ◽  
Vol 107 (1) ◽  
pp. 241-249 ◽  
Author(s):  
Ning Gao ◽  
Mohamed Rahmani ◽  
Xianglin Shi ◽  
Paul Dent ◽  
Steven Grant
Keyword(s):  
Oxidative Damage ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Free Radical Scavengers ◽  
Leukemia Cells ◽  
Human Leukemia ◽  
Caspase Activation ◽  
Down Regulation ◽  
Mitochondrial Injury ◽  
Human Leukemia Cells

Abstract Interactions between the endogenous estradiol metabolite 2-medroxyestradiol (2-ME) and histone deacetylase inhibitors (HDACIs) have been investigated in human leukemia cells. Coadministration of subtoxic or marginally toxic concentrations of 2-ME and SAHA or sodium butyrate in diverse human leukemia-cell types resulted in a marked increase in oxidative damage (eg, generation of reactive oxygen species [ROSs]), mitochondrial injury (eg, cytochrome c release and Bax translocation), caspase activation, and apoptosis. These interactions were also noted in primary human leukemia cells but not in normal bone marrow CD34+ cells. Synergistic interactions between these agents were associated with inactivation of Akt and activation of c-Jun N-terminal kinase (JNK). Essentially all of these events were reversed by free radical scavengers such as the manganese superoxide dismutase (MnSOD) mimetic TBAP and catalase. Notably, treatment with 2-ME/HDACIs resulted in down-regulation of thioredoxin, MnSOD, and glutathione peroxidase. Enforced activation of Akt blocked 2-ME/HDACI-mediated mitochondrial injury, caspase activation, and JNK up-regulation, but not generation of ROSs. Pharmacologic or genetic (siRNA) interruption of the JNK pathway also significantly attenuated the lethality of this regimen. Together, these findings support a model in which antileukemic synergism between 2-ME and HDACIs stems primarily from induction of oxidative damage, leading in turn to Akt inactivation and JNK activation, culminating in mitochondrial injury and apoptosis. They also raise the possibility that these events may preferentially occur in leukemic versus normal hematopoietic cells.

scholarly journals Oleanolic Acid Induces Apoptosis in Human Leukemia Cells through Caspase Activation and Poly(ADP-ribose) Polymerase Cleavage

2007 ◽  
Vol 39 (10) ◽  
pp. 803-809 ◽  
Author(s):  
Pengxia ZHANG ◽  
Hongmei LI ◽  
Dong CHEN ◽  
Juhua NI ◽  
Yuming KANG ◽  
...  
Keyword(s):  
Oleanolic Acid ◽  
Leukemia Cells ◽  
Human Leukemia ◽  
Caspase Activation ◽  
Human Leukemia Cells

Induction of mitochondrial permeability transition and cytochrome C release in the absence of caspase activation is insufficient for effective apoptosis in human leukemia cells

Blood ◽  
2000 ◽  
Vol 95 (5) ◽  
pp. 1773-1780 ◽  
Author(s):  
Jayshree L. Hirpara ◽  
Mohamed A. Seyed ◽  
Kok W. Loh ◽  
Hui Dong ◽  
R. Manjunatha Kini ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Tumor Cells ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Leukemia Cells ◽  
Human Leukemia ◽  
Caspase Activation ◽  
Cytochrome C Release ◽  
Membrane Pore ◽  
Human Leukemia Cells

Induction of mitochondrial permeability transition (MPT) and cytosolic translocation of cytochrome C are considered essential components of the apoptotic pathway. Hence, there is the realization that mitochondrial-specific drugs could have potential for use as chemotherapeutic agents to trigger apoptosis in tumor cells. Recently, we showed that photoproducts of merocyanine 540 (pMC540) induced tumor cell apoptosis. In this study, we focused on identifying mitochondrial-specific compounds from pMC540 and studied their apoptotic potential. One purified fraction, C5, induced a drop in mitochondrial transmembrane potential and cytosolic translocation of cytochrome C in HL60 human leukemia cells. Moreover, the addition of C5 to purified rat liver mitochondria induced MPT as indicated by mitochondrial matrix swelling, which was completely inhibited by cyclosporin A, an inhibitor of the inner-membrane pore. Supernatant of C5-treated mitochondria showed a dose-dependent increase in cytochrome C, which was also inhibited in the presence of cyclosporin A, strongly indicating a direct effect on the inner-membrane pore. Despite the strong mitochondrial reactivity, C5 elicited minimal cytotoxicity (less than 25%) against HL60 leukemia and M14 melanoma cells because of inefficient caspase activation. However, prior exposure to C5 significantly enhanced the apoptotic response to etoposide or the CD95 receptor. Thus, we demonstrate that MPT induction and cytochrome C release by the novel compound C5, in the absence of effective caspase activation, is insufficient for triggering efficient apoptosis in tumor cells. However, when used in combination with known apoptosis inducers, such compounds could enhance the sensitivity of tumor cells to apoptosis.

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