Apoptosis induced by sodium butyrate treatment increases immunogenicity of a rat colon tumor cell line

Boisteau, Olivier; Gautier, Fabien; Cordel, Sandrine; Henry, Frédéric; Harb, Jean; Douillard, Jean-Yves; Vallette, François M.; Méflah, Khaled; Grégoire, Marc

doi:10.1023/a:1026461825570

Cited by 24 publications

(19 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, although butyrate arrests normal cells in G 1 , it induces apoptosis in transformed cells within 4 hours after G 1 -S arrest. 58,[65][66][67][68][69][70][71][72][73][74][75][76][77] Thus, the activities of butyrate that cause cell cycle arrest may be problematic when the drug is used in patients with hemoglobinopathies unless it is given intermittently, which, in turn, limits the amount of ␥-globin and the proportions of F cells that can be induced.…”

Section: Discussionmentioning

confidence: 99%

Short-chain fatty acid derivatives stimulate cell proliferation and induce STAT-5 activation

Boosalis

Bandyopadhyay

Bresnick

et al. 2001

Blood

View full text Add to dashboard Cite

Current chemotherapeutic and butyrate therapeutics that induce fetal hemoglobin expression generally also suppress erythropoiesis, limiting the production of cells containing fetal hemoglobin (F cells). Recently, selected short-chain fatty acid derivatives (SCFADs) were identified that induce endogenous ␥-globin expression in K562 cells and human burst-forming units-erythroid and that increase proliferation of human erythroid progenitors and a multilineage interleukin-3-dependent hematopoietic cell line. In this report, ␥-globin inducibility by these SCFADs was further demonstrated in mice transgenic for the locus control region and the entire ␤-globin gene locus in a yeast artificial chromosome and in 2 globin promoter-reporter assays. Conditioned media experiments strongly suggest that their proliferative activity is a direct effect of the test compounds. Investigation of potential mechanisms of action of these SCFADs demonstrates that these compounds induce prolonged expression of the growth-promoting genes c-myb and c-myc. Both butyrate and specific growth-stimulatory SCFADs induced prolonged signal transducer and activator of transcription (STAT)-5 phosphorylation and activation, and c-cis expression, persisting for more than 120 minutes, whereas with IL-3 alone phosphorylation disappeared within minutes. In contrast to butyrate treatment, the growth-stimulating SCFADs did not result in bulk histone H4 hyperacetylation or induction of p21 Waf/Cip , which mediates the suppression of cellular growth by butyrate. These findings suggest that the absence of bulk histone hyperacetylation and p21 induction, but prolonged induction of cis, myb, myc, and IntroductionButyrate analogs have been of interest as potential therapeutics for the ␤-globin disorders following the demonstration that butyrate could transcriptionally activate developmentally silenced fetal and embryonic globin genes in many experimental conditions. [1][2][3][4][5][6][7][8][9][10][11] In clinical trials, arginine butyrate stimulated hemoglobin F (HbF) synthesis to levels above 20% and induced a nearly 2-fold increase in the amount of HbF/cell and in proportions of red blood cells expressing HbF (F reticulocytes) in patients with sickle cell anemia. [10][11][12] With constant use, however, the activity of the drug in maintaining substantial increases in HbF-containing erythrocytes gradually decreased. 13 We hypothesized that this tachyphylaxis was due to the coincident cellular growth-inhibitory properties of butyrate and developed intermittent or "pulse" regimens (4 days of use per month) to surmount this problem. 12 Although this regimen proved effective, it also imposed severe limitations on the amount of drug that can be delivered to the patient. An orally bioavailable transcriptional inducer of ␥-globin that does not have cellular growth-inhibitory properties and could be administered more frequently to stimulate a further increase in the proportion of HbF-containing cells (F cells) would be therapeutically advantageous for ␤-globin disord...

show abstract

Section: Discussionmentioning

confidence: 99%

Short-chain fatty acid derivatives stimulate cell proliferation and induce STAT-5 activation

Boosalis

Bandyopadhyay

Bresnick

et al. 2001

Blood

View full text Add to dashboard Cite

show abstract

“…Apoptotic bodies were prepared and purified as previously described [6]. Briefly, PROb were treated for 3 days with sodium butyrate (5 mM).…”

Section: Generation Of Apoptotic Cellsmentioning

confidence: 99%

“…In order to evaluate the implication of apoptotic bodies in curative treatments of tumor-bearing rats, we developed a therapy which included injections of apoptotic bodies from tumor cells [6]. Briefly, 10 days after intraperitoneal injection of cancer cells, treatment with apoptotic bodies and IL2 was performed ( fig.…”

Section: Curative Treatments Of Tumor-bearing Rats With Apoptotic Bodiesmentioning

confidence: 99%

Role of Antigen-Presenting Cells in Long-Term Antitumor Response Based on Tumor-Derived Apoptotic Body Vaccination

Henry

Bretaudeau²,

Hequet³

et al. 1999

Pathobiology

Self Cite

View full text Add to dashboard Cite

Cellular therapy prospects for cancer are based on the development of T cell response, resulting in efficient tumor rejection and long-term protection. We have previously shown that treatment combining injection of interleukin-2 and tumor-derived apoptotic bodies, but not tumor cell extracts, permits to reject parental tumor in 40% of rats. We observed the implication of antigen-presenting cells (APCs) and tumor-derived apoptotic bodies in the rejection of established peritoneal carcinomatosis. We demonstrated that apoptotic bodies could be efficiently phagocytosed by monocytes, triggering them to an APC phenotype. When using these phagocytosing APCs, derived from peritoneal or blood monocytes, the remission rate reached 80% of rats. However, due to the lack of specific markers of rat monocyte-derived cells, the precise role of APCs, dendritic cells and/or macrophages responsible for this therapeutic improvement remained to be clarified. In order to elucidate this question, we developed an in vivo preventive cellular therapy based on tumor-derived apoptotic bodies, where macrophages were either depleted or activated. We report here that in a preventive antitumoral apoptotic body vaccination that allows survival for 40% of treated rats, the antitumor response was characterized by a specific long-term memory (cured rats rejected a second parental tumor cell challenge). Depletion of resident macrophages with silica or clodronate liposomes appeared to promote apoptotic body vaccination efficiency, increasing the treatment to 66% of success. In this case, FACS analysis showed that peritoneal cells present are essentially immature APCs and freshly recruited NK cells. In contrast, the onset of peritoneal inflammation by thioglycollate, inducing massive recruitment and activation of macrophages, reduced the overall survival, whatever the treatment was. Also, even though the surviving rate was better in silica-treated rats than control, no long-term protection was elicited. Our data suggest that massive inflammation, recruiting numerous activated macrophages, could inhibit tumor antigen presentation by ‘professional’ APCs having phagocytosed apoptotic bodies, and defavor a specific antitumoral T cell response. Although effective responses were developed against parental tumor cells with silica/apoptotic body treatment, they seemed only partial, limited to primary cytotoxic efficiency. In conclusion, even if macrophages did not appear necessary for a primary response to tumor cells, these cells seemed to be implicated in the establishment of memory and long-term antitumor response.

show abstract

“…It was shown that DC pulsed with apoptotic tumor cells induce a strong Ag-specific T cell response in vitro, and when injected into mice, such pulsed DC induced tumor-specific cytotoxic T cell responses and long-term protection from parental tumor challenge (24) (in these models, DC activation might result from the in vitro manipulation of the DC). It was also suggested that an increase of the apoptotic process in poorly immunogenic tumor cells can lead to a remission of established peritoneal carcinomatosis (25), and more recently, that apoptotic but not necrotic tumor cells are efficient vaccines in vivo (26). Using the RMA T cell lymphoma model, it was demonstrated that the injection of apoptotic tumor cells results in the priming of a functional long-lasting tumor-specific immune response, and that this occurs via cross-priming (27).…”

mentioning

confidence: 99%

T Cell Immunity Induced by Live, Necrotic, and Apoptotic Tumor Cells

Bartholomae

Rininsland

Eisenberg

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

The rules that govern the engagement of antitumor immunity are not yet fully understood. Ags expressed by tumor cells are prone to induce T cell tolerance unless the innate immune system is activated. It is unclear to what extent tumors engage this second signal link by the innate immune system. Apoptotic and necrotic (tumor) cells are readily recognized and phagocytosed by the cells of the innate immune system. It is unknown how this affects the tumor’s immunogenicity. Using a murine melanoma (B16m) and lymphoma (L5178Y-R) model, we studied the clonal sizes and cytokine signatures of the T cells induced by these tumors in syngeneic mice when injected as live, apoptotic, and necrotic cells. Both live tumors induced a type 2 CD4 cell response characterized by the prevalent production of IL-2, IL-4, and IL-5 over IFN-γ. Live, apoptotic, and necrotic cells induced CD4 (but no CD8) T cells of comparable frequencies and cytokine profiles. Therefore, live tumors engaged the second signal link, and apoptotic or necrotic tumor cell death did not change the magnitude or quality of the antitumor response. A subclone of L5178Y-R, L5178Y-S cells, were found to induce a high-frequency type 1 response by CD4 and CD8 cells that conveyed immune protection. The data suggest that the immunogenicity of tumors, and their characteristics to induce type 1 or type 2, CD4 or CD8 cell immunity is not primarily governed by signals associated with apoptotic or necrotic cell death, but is an intrinsic feature of the tumor itself.

show abstract

Apoptosis induced by sodium butyrate treatment increases immunogenicity of a rat colon tumor cell line

Cited by 24 publications

References 14 publications

Short-chain fatty acid derivatives stimulate cell proliferation and induce STAT-5 activation

Short-chain fatty acid derivatives stimulate cell proliferation and induce STAT-5 activation

Role of Antigen-Presenting Cells in Long-Term Antitumor Response Based on Tumor-Derived Apoptotic Body Vaccination

T Cell Immunity Induced by Live, Necrotic, and Apoptotic Tumor Cells

Contact Info

Product

Resources

About