(–)Gossypol and its combination with imatinib induce apoptosis in human chronic myeloid leukemic cells

Yang, Meng; Li, Yan; Li, Jing; Li, Hongyan; Fu, Jianjiang; Liu, Yue; He, Liang; Chen, Xiaoguang

doi:10.1080/10428190701583991

Cited by 18 publications

(9 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3). On the other hand, apoptosis of K562 cells has been reported to be mediated by the down-regulation of an anti-apoptotic protein, Bcl-xL, although the mechanisms decreasing Bcl-xL expression depend on stimuli [21][22][23]. Compound 7 continued to decrease the expression of BclxL from 6 h after the treatment (Fig.…”

Section: Discussionmentioning

confidence: 88%

Liquid crystal-related compound-induced cell growth suppression and apoptosis in the chronic myelogenous leukemia K562 cell line

et al. 2010

View full text Add to dashboard Cite

Liquid crystals are the state of matter existing between the liquid and the crystalline phase, and there is a recent surging interest in its biological effects. Our previous study showed that liquid crystal-related compounds (LCRCs), which are precursors of the liquid crystal, enhanced hematopoietic differentiation at a relatively low concentration (Biol Pharm Bull, 32, 2009). However, biological potentials of LCRCs on tumor cells are unclear. In this study, the biological activity of 16 LCRCs to a chronic myelogenous leukemia cell line, K562, was evaluated. As a result, two compounds, 2-(4-butoxyphenyl)-5-(4-hydroxyphenyl)pyrimidine (compound 7) and 2-{4-(4-hexyloxyphenyl)phenyl}-5-hydroxypyrimidine (compound 9) showed marked growth suppression of K562 cells at μM range. These compounds are similar in structure with a core of three aromatic rings including a pyrimidine ring and residues of one alkyl chain and one hydroxide on either side. In addition, only compound 7 induced the activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, and apoptosis of K562 cells. The contrasting results between compounds 7 and 9 indicate different mechanisms to suppress the cell proliferation between the two compounds. These results suggest the possibility of LCRCs for application as new antitumor drugs.

show abstract

Section: Discussionmentioning

confidence: 88%

Liquid crystal-related compound-induced cell growth suppression and apoptosis in the chronic myelogenous leukemia K562 cell line

et al. 2010

View full text Add to dashboard Cite

show abstract

“…While BCL2 inhibition has been previously explored in CML, most studies have focused on CML cell lines (Kuroda et al, 2006; Meng et al, 2007) or CD34 + cells grown in culture (Mak et al, 2011) rather than self-renewing CML BC LSC in selective niches. Moreover, published reports do not address the potential antithetical roles of BCL2 family splice isoforms or the role of the microenvironment in promoting LSC survival.…”

Section: Discussionmentioning

confidence: 99%

A Pan-BCL2 Inhibitor Renders Bone-Marrow-Resident Human Leukemia Stem Cells Sensitive to Tyrosine Kinase Inhibition

et al. 2013

View full text Add to dashboard Cite

Summary Leukemia stem cells (LSC) play a pivotal role in chronic myeloid leukemia (CML) tyrosine kinase inhibitor (TKI) resistance and progression to blast crisis (BC), in part, through alternative splicing of self-renewal and survival genes. To elucidate splice isoform regulators of human BC LSC maintenance, we performed whole transcriptome RNA sequencing; splice isoform-specific qRT-PCR, nanoproteomics, stromal co-culture and BC LSC xenotransplantation analyses. Cumulatively, these studies show that alternative splicing of multiple pro-survival BCL2 family genes promotes malignant transformation of myeloid progenitors into BC LSC that are quiescent in the marrow niche and contribute to therapeutic resistance. Notably, a novel pan-BCL2 inhibitor, sabutoclax, renders marrow niche-resident BC LSC sensitive to TKIs at doses that spare normal progenitors. These findings underscore the importance of alternative BCL2 family splice isoform expression in BC LSC maintenance and suggest that combinatorial inhibition of pro-survival BCL2 family proteins and BCR-ABL may eliminate dormant LSC and obviate resistance.

show abstract

“…It can block Bcl-XL heterodimerization with Bax or Bad, and promote caspase-3 activation and cytochrome c release in Bcl-2 and Bcl-XL overexpressing cells (Meng et al, 2008; Oliver et al, 2005; Shiau et al, 2006). Since gossypol exhibited potent killing in multiple cancer cells (Meng et al, 2007; Vetvicka et al, 2007), it has been introduced into clinical trials in CLL, hormone refractory prostate cancer, and advanced breast cancer (Politzer, 2008; Stein et al, 1992; Van Poznak et al, 2001). Several gossypol derivatives are currently under development as potential anticancer agents.…”

Section: Small Molecules That Directly Target Mitochondriamentioning

confidence: 99%

Small mitochondria-targeting molecules as anti-cancer agents

Wang

Ogasawara

Huang

2010

Molecular Aspects of Medicine

125

View full text Add to dashboard Cite

Alterations in mitochondrial structure and functions have long been observed in cancer cells. Targeting mitochondria as a cancer therapeutic strategy has gained momentum in the recent years. The signaling pathways that govern mitochondrial function, apoptosis and molecules that affect mitochondrial integrity and cell viability have been important topics of the recent review in the literature. In this article, we first briefly summarize the rationale and biological basis for developing mitochondrial-targeted compounds as potential anticancer agents, and then provide key examples of small molecules that either directly impact mitochondria or functionally affect the metabolic alterations in cancer cells with mitochondrial dysfunction. The main focus is on the small molecular weight compounds with potential applications in cancer treatment. We also summarize information on the drug developmental stages of the key mitochondria-targeted compounds and their clinical trial status. The advantages and potential shortcomings of targeting the mitochondria for cancer treatment are also discussed.

show abstract

(–)Gossypol and its combination with imatinib induce apoptosis in human chronic myeloid leukemic cells

Cited by 18 publications

References 27 publications

Liquid crystal-related compound-induced cell growth suppression and apoptosis in the chronic myelogenous leukemia K562 cell line

Liquid crystal-related compound-induced cell growth suppression and apoptosis in the chronic myelogenous leukemia K562 cell line

A Pan-BCL2 Inhibitor Renders Bone-Marrow-Resident Human Leukemia Stem Cells Sensitive to Tyrosine Kinase Inhibition

Small mitochondria-targeting molecules as anti-cancer agents

Contact Info

Product

Resources

About