Bcl-2 related proteins are dramatically induced at the early stage of differentiation in human liver cancer cells by a histone deacetylase inhibitor projecting an anti-apoptotic role during this period.

Wakabayashi, Kanji; Saito, Hidetsugu; Ebinuma, Hirotoshi; Saito, Yoshimasa; Takagi, Toshikazu; Nakamura, Masaru; Umezawa, Akihiro; Hata, Junichi; Ishii, Hiromasa

doi:10.3892/or.7.2.285

Cited by 21 publications

(24 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As shown by several papers, it inhibits apoptosis induced by several stimuli, improving the ability of tumor cells to escape from therapy (12,13). Moreover, as reported in this study, bclxL overexpression increases the expression of CXCL8, an endogenous inducer of in vitro and in vivo angiogenesis (28).…”

Section: Discussionmentioning

confidence: 60%

“…bcl-xL is a prosurvival multidomain protein that, in addition to promoting cell survival (11), has been implicated in the regulation of cell cycle (12), in the modulation of cell differentiation (13), and in the resolution of inflammation (14). A pivotal role for bcl-xL in breast cancer metastatization (15) and in anaplastic lymphoma kinase -mediated oncogenicity (16) has also been shown.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Modulation of bcl-xL in Tumor Cells Regulates Angiogenesis through CXCL8 Expression

Giorgini

Trisciuoglio

Gabellini

et al. 2007

Molecular Cancer Research

View full text Add to dashboard Cite

In this paper, we investigated whether bcl-xL can be involved in the modulation of the angiogenic phenotype of human tumor cells. Using the ADF human glioblastoma and the M14 melanoma lines, and their derivative bcl-xL -overexpressing clones, we showed that the conditioned medium of bcl-xL transfectants increased in vitro endothelial cell functions, such as proliferation and morphogenesis, and in vivo vessel formation in Matrigel plugs, compared with the conditioned medium of control cells. Moreover, the overexpression of bcl-xL induced an increased expression of the proangiogenic interleukin-8 (CXCL8), both at the protein and mRNA levels, and an enhanced CXCL8 promoter activity. The role of CXCL8 on bcl-xL -induced angiogenesis was validated using CXCL8-neutralizing antibodies, whereas down-regulation of bcl-xL through antisense oligonucleotide or RNA interference strategies confirmed the involvement of bcl-xL on CXCL8 expression. Transient overexpression of bcl-xL led to extend this observation to other tumor cell lines with different origin, such as colon and prostate carcinoma. In conclusion, our results showed that CXCL8 modulation by bcl-xL regulates tumor angiogenesis, and they point to elucidate an additional function of bcl-xL protein. (Mol Cancer Res 2007;5(8):761 -71)

show abstract

Section: Discussionmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Modulation of bcl-xL in Tumor Cells Regulates Angiogenesis through CXCL8 Expression

Giorgini

Trisciuoglio

Gabellini

et al. 2007

Molecular Cancer Research

View full text Add to dashboard Cite

show abstract

“…Bcl-2, Bax and p53 affect the proliferation, apoptosis, occurrence and development of PCa (22,23). Among the genes involved in the regulation of cell apoptosis, Bcl-2 is currently recognized as an anti-apoptotic gene (24), which participates in the occurrence of tumors by inhibiting cell apoptosis and prolonging cell survival (25). The present results revealed that treatment with DPPT significantly reduced p-Akt protein expression, and increased p53 and Bax protein expression in DU-145 cells.…”

Section: Discussionmentioning

confidence: 99%

Anticancer effect of deoxypodophyllotoxin induces apoptosis of human prostate cancer cells

Zhou

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

Abstract. Deoxypodophyllotoxin (DPPT) is extracted and separated from citrus-related plants, including Podophyllum (P.) peltatum, P. pleianthum, P. emodi (also called P. hexandrum) and Diphylleia grayi. DPPT has significant antitumor and antiviral activity. However, due to its strong toxicity and side effects, its use is limited in practical applications. The in vitro antitumor efficacy of DPPT on human prostate cancer (PCa) cells remains to be determined. The present study investigated the anticancer effect of DPPT on human PCa cells and its potential mechanism. The data revealed that DPPT markedly reduced cell proliferation and activated the caspase-3 expression level by an increase in apoptotic cell death in DU-145 cells. In addition, treatment with DPPT markedly downregulated the levels of phosphorylated Akt and activated the p53/B-cell lymphoma 2 associated X protein (Bax)/phosphatase and tensin homolog (PTEN) signaling pathway in DU-145 cells, suggesting that caspase-mediated pathways were involved in DPPT-induced apoptosis. The present study suggested the role of DPPT as a novel chemotherapeutic drug for human PCa, which may function through the Akt/p53/Bax/PTEN signaling pathway.

show abstract

“…A similar role has been ascribed to MCL1 in the other types of differentiating cells, and to BCL2 in still others. [16][17][18][19] In addition to transfected cell lines, transgenic mice have been generated that express an introduced human MCL1 transgene in hematopoietic tissues. 20 The MCL1 transgene was expressed at levels that are seen endogenously (eg upon stimulation with TPA), and was found to produce moderate viability enhancement.…”

Section: Mcl1 Promotes Short-term Viability In a Variety Of Cell Typesmentioning

confidence: 99%

MCL1 provides a window on the role of the BCL2 family in cell proliferation, differentiation and tumorigenesis

2002

Leukemia

251

245

View full text Add to dashboard Cite

The MCL1 gene (myeloid cell leukemia-1) was discovered serendipitously about a decade ago and proved to be a member of the emerging BCL2 gene family. Ongoing studies of this gene provide an interesting perspective on the role of the BCL2 family in transitions in cell phenotype. Specifically, gene products that influence cell viability as a major effect (eg MCL1, BCL2 and other family members) can act as key determinants in cell proliferation, differentiation and tumorigenesis. Although they do not have a direct role in proliferation/differentiation programs, these genes can either permit these programs to proceed or prevent them. Through such effects, the BCL2 family regulates the normal flow of cells through cycles of proliferation and along various pathways of differentiation. A model is presented suggesting that this is accomplished by sustaining or inhibiting viability at critical points in the cell lifecycle. These critical points represent windows of time during which cell fate transitions are effected. They can also be visualized as windows that open or close to promote or prevent continued progression along various cell fate pathways. The pattern of BCL2 family expression at these points allows for the proliferation differentiation, and continued viability of cell types that are needed, while aborting these processes for cells that are overabundant or no longer needed. The combined action of the various family members can therefore control the fate of cells, tissues and even the organism. This mechanism involving apoptosis-related genes is readily executable, and is poised to respond to external signals through the differential regulation of BCL2 family members. As such, it plays an important role in the maintenance of tissue homeostasis and function. Alterations that affect the BCL2 family impair the capacity to control the flow of cells through these critical points, and thereby 'leave the window open' for cell immortalization and cancer. Targeting this family may thus provide a means of inhibiting cancer development and inducing apoptosis in tumor cells. Leukemia (2002) 16, 444-454. DOI: 10.1038/sj/leu/2402416 Keywords: MCL1; BCL2; apoptosis; differentiation; hematopoiesis; cancer MCL1 was discovered based on increased expression during cell commitment to differentiation MCL1 was originally identified as a gene up-regulated early in the differentiation of a human myeloid leukemia cell line, ML-1. 1 These cells proliferate at an immature myeloblastic stage and undergo terminal differentiation to non-proliferative monocyte/macrophages upon exposure to phorbol esters such as 12-0-tetradecanoylphorbol 13-acetate (TPA). Commitment to differentiation occurs rapidly -within a window of several hours -upon the application of TPA to growth-arrested cells. 2 The 'commitment window' precedes phenotypic differentiation, which proceeds over the next several days. ML-1 cells that have passed through the commitment window do not difCorrespondence: RW Craig, Department of Pharmacology and Toxicology, Dartmouth Medic...

show abstract

Bcl-2 related proteins are dramatically induced at the early stage of differentiation in human liver cancer cells by a histone deacetylase inhibitor projecting an anti-apoptotic role during this period.

Cited by 21 publications

References 0 publications

Modulation of bcl-xL in Tumor Cells Regulates Angiogenesis through CXCL8 Expression

Modulation of bcl-xL in Tumor Cells Regulates Angiogenesis through CXCL8 Expression

Anticancer effect of deoxypodophyllotoxin induces apoptosis of human prostate cancer cells

MCL1 provides a window on the role of the BCL2 family in cell proliferation, differentiation and tumorigenesis

Contact Info

Product

Resources

About