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PubMed2001

Evidence of a functional role for the cyclin-dependent kinase-inhibitor p21WAF1/CIP1/MDA6 in promoting differentiation and preventing mitochondrial dysfunction and apoptosis induced by sodium butyrate in human myelomonocytic leukemia cells (U937).

The impact of dysregulation of the cyclin-dependent kinase inhibitor p21WAF1/CIP1/MDA6 has been examined in U937 human monocytic leukemia cells in relation to cell cycle arrest and differentiation following treatment with the histone deacetylase inhibitor sodium butyrate (SB). Cells stably transfected with a p21WAF1/CIP1/MDA6 antisense construct, in marked contrast to their wild-type counterparts, failed to up-regulate p21WAF1/CIP1/MDA6, undergo G1 arrest, or express the maturation marker CD11b when exposed to 1 or 3 mM SB. However, antisense-expressing cells were significantly more susceptible to SB-mediated mitochondrial injury and apoptosis, manifested by increased cytosolic translocation of cytochrome c, activation of pro-caspase 3, and degradation of PARP. Dysregulation of p21WAF1/CIP1/MDA6 did not modify the extent of SB-induced histone acetylation, but did result in cleavage of p27KIP1, Bcl-2 and pRb, as well as diminished levels of full-length underphosphorylated pRb. Finally, dysregulation of p21WAF1/CIP1/MDA6 did not modify SB-mediated down-regulation of E2F-1 or c-Myc, but was associated with enhanced down-regulation of cyclins D1 and E. Together, these findings indicate that in U937 leukemia cells, p21WAF1/CIP1/MDA6 plays a critical functional role in SB-mediated G1 arrest and maturation, and suggest that cells displaying dysregulation of this CDKI respond to SB by engaging a default apoptotic program.

Apoptosis↗
PubMed2007

Dose-dependent reduction of dietary protein-induced colonocyte DNA damage by resistant starch in rats correlates more highly with caecal butyrate than with other short chain fatty acids.

Previous studies have shown increased levels of colonocyte DNA damage (as measured by the comet assay) and thinning of the colonic mucus layer in rats fed higher dietary protein as casein or red meat with highly digestible starch. Feeding resistant starch (RS) as high amylose maize starch (HAMS) opposed these changes. However, the dietary level of HAMS was relatively high (48% by weight) so this study was conducted to establish whether HAMS had the same effects at lower dietary levels. Adult male rats were fed a diet containing 25% casein with 0%, 10%, 20%, 30% or 40% HAMS for 4 wk. DNA single strand breaks and 8-hydroxyguanosine levels were measured in isolated colonocytes by the comet assay. As expected, comet tail moment was greatest and the mucus barrier thinnest in rats fed 0% HAMS. DNA damage was reduced and the mucus barrier thickened in a logarithmic dose-dependent manner by HAMS. There was no significant difference in 8-hydroxyguanosine between dietary groups. Caecal and fecal short chain fatty acid (SCFA) pools rose with the increased level of dietary HAMS. DNA damage of colonocytes correlated negatively with caecal SCFA but the strongest correlation was with caecal butyrate, which is consistent with the proposed role of this SCFA in promoting a normal cell phenotype. These data show that HAMS prevents protein-induced colonic DNA damage in a dose-dependent manner. Inclusion of 10% HAMS was found to be sufficient to oppose colonocyte DNA damage, and to increase caecal and fecal SCFA pools.

Animals↗
PubMed2000

Equations and calculations for fermentations of butyric acid bacteria. Reprinted from Biotechnology and Bioengineering, Vol. XXVI, Pp 174-187 (1984).

A stoichiometric equation has been derived which describes the interrelations among the various products and biomass in fermentations of butyric acid bacteria. The derivation of the equation is based on an assumed ATP yield, two biological regularities, and the biochemistry of product formation of the fermentations. The equation obeys the constraints imposed on growth and product formation by thermodynamics and the biochemical topology. The validity of the equation is tested using a variety of fermentation data from the literature. The uses, improvements, limitations, and extensions of the equation are also discussed in detail. For example, the fermentation equation is used to calculate the maximal possible yields of the main fermentation products.

Bacteria↗
PubMed1999

Sodium butyrate modulates p53 and Bcl-2 expression in human retinoblastoma cell lines.

Sodium butyrate (SB) is a potent biological modifier that can induce diverse effects including growth inhibition, differentiation, or apoptosis of many cell types including retinoblastoma (Rb), and modulation of genes such as c-fos and p53. In this study we assessed the effects of SB on cell growth and expression of p53, critical for cell cycle control, and Bcl-2, an inhibitor of apoptosis, in two human Rb cell lines (Y79 and WERI-Rb1). Attachment cultures were treated with 1 mM SB for up to 5 days and immunocytochemistry was used to examine for the expression of neural cell adhesion molecule (NCAM), p53, and Bcl-2. Suspension cultures of both cell lines were also treated with 1 and 4 mM SB, and at selected times cell extracts were prepared and the expression of p53 and Bcl-2 proteins determined by Western blot analysis. Treatment with 1 mM SB of both cell lines for 5 days inhibited growth and induced morphological changes including extension of neurite-like processes. Up to 12 h after 1 mM SB treatment, p53 and Bcl-2 expressions were similar to control levels, then gradually decreased to very low levels at 5 days. SB (4 mM) also inhibited growth associated with cell death, which was apparent at 24 h posttreatment. Expressions of p53 and Bcl-2 were decreased below control levels at 4 h, and by 24 h only very low levels of protein were detected. SB-induced modulation of p53 and Bcl-2 expression may have implications for controlling Rb growth, particularly in combination with chemotherapy drugs, which are increasingly used in the treatment of Rb.

Butyrates↗
PubMedDate not supplied

Induction of apoptosis in human gastric cancer by sodium butyrate.

BACKGROUND: Novel therapeutic agents are needed in the adjuvant treatment of gastric cancer. The differentiating agent sodium butyrate (NaBT) inhibits the growth of colon cancer cells; its effects on gastric cancers are not known. The purpose of our study was to characterize the effects of NaBT on human gastric cancer. MATERIAL & METHODS: The human gastric cancer, SIIA, was treated with NaBT (5 mM) for 12-72 h. Cell number, viability and death were measured. Expression levels of the tumor-suppressor protein, p53, the cell-cycle inhibitors, p21Waf1/Cip1 and p27Kip1, and the pro-apoptotic proteins, Bax, Bak, and Bik, were determined. RESULTS: NaBT significantly inhibited SIIA gastric cancer cell proliferation in a time-dependent fashion by a process involving the induction of apoptosis. Treatment with NaBT was associated with increased expression levels of p21Waf1/Cip1 p27Kip1, Bax, Bak, and Bik. CONCLUSIONS: NaBT triggers growth arrest and apoptosis in the human gastric cancer SIIA potentially through the induction of the cell-cycle inhibitors, p21Waf1/Cip1 and p27Kip1, and the proapoptotic genes, Bax, Bak, and Bik. NaBT may be an effective adjuvant agent in the treatment of gastric cancer.

Apoptosis↗
PubMed2000

Hemoglobin switching in unicellular erythroid culture of sibling erythroid burst-forming units: kit ligand induces a dose-dependent fetal hemoglobin reactivation potentiated by sodium butyrate.

Mechanisms underlying fetal hemoglobin (HbF) reactivation in adult life have not been elucidated; particularly, the role of growth factors (GFs) is controversial. Interestingly, histone deacetylase (HD) inhibitors (sodium butyrate, NaB, trichostatin A, TSA) reactivate HbF. We developed a novel model system to investigate HbF reactivation: (1) single hematopoietic progenitor cells (HPCs) were seeded in serum-free unilineage erythroid culture; (2) the 4 daughter cells (erythroid burst-forming units, [BFU-Es]), endowed with equivalent proliferation/differentiation and HbF synthesis potential, were seeded in 4 unicellular erythroid cultures differentially treated with graded dosages of GFs and/or HD inhibitors; and (3) HbF levels were evaluated in terminal erythroblasts by assay of F cells and gamma-globin content (control levels, 2.4% and 1.8%, respectively, were close to physiologic values). HbF was moderately enhanced by interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor treatment (up to 5%-8% gamma-globin content), while sharply reactivated in a dose-dependent fashion by c-kit ligand (KL) and NaB (20%-23%). The stimulatory effects of KL on HbF production and erythroid cell proliferation were strictly correlated. A striking increase of HbF was induced by combined addition of KL and NaB or TSA (40%-43%). This positive interaction is seemingly mediated via different mechanisms: NaB and TSA may modify the chromatin structure of the beta-globin gene cluster; KL may activate the gamma-globin promoter via up-modulation of tal-1 and possibly FLKF transcription factors. These studies indicate that KL plays a key role in HbF reactivation in adult life. Furthermore, combined KL and NaB administration may be considered for sickle cell anemia and beta-thalassemia therapy.

Adult↗
PubMed2000

Activation of lytic Epstein-Barr virus (EBV) infection by radiation and sodium butyrate in vitro and in vivo: a potential method for treating EBV-positive malignancies.

The consistent presence of the EBV genome in certain tumors offers the potential for novel EBV-directed therapies. Switching the latent form of EBV infection present in most EBV-positive tumor cells into the cytolytic form may be clinically useful because lytic EBV infection leads to host cell destruction, and very few normal cells contain the EBV genome. It would also be therapeutically advantageous to induce expression of EBV-encoded lytic proteins that convert the nucleoside analogues ganciclovir (GCV) and 3'-azido-3'deoxythymidine (AZT) into their active, cytotoxic forms. In this report, we have explored two different approaches for activating the lytic form of EBV infection in tumors. We show that gamma-irradiation at clinically relevant doses induces lytic EBV infection in lymphoblastoid cell lines in vitro as well as in EBV-positive B-cell tumors in SCID mice. In addition, sodium butyrate (given as a single i.p. dose) is effective for activating lytic viral infection in some EBV tumor types in SCID mice. We also examined whether low-dose gamma-irradiation treatment of EBV-positive lymphoblastoid cells in vitro promotes GCV or AZT susceptibility. The combination of radiation with either GCV or AZT induced significantly more cell killing in vitro than either radiation or prodrug treatment alone. Most importantly, we found that the combination of gamma-irradiation and GCV was much more effective in treating EBV-positive lymphoblastoid tumors in SCID mice than either agent alone. Thus, GCV or AZT treatment could potentially enhance the therapeutic efficacy of radiation therapy for EBV-positive lymphomas in patients.

Animals↗
PubMed1999

Combination of all-trans retinoic acid with butyric acid and its prodrugs markedly enhancing differentiation of human acute promyelocytic leukemia NB4 cells.

OBJECTIVE: To use NB4, an authentic human acute promyelocytic leukemia cell line, as well as the marrow cells from patients with acute promyelocytic leukemia (APL), containing the PML/RAR alpha fusion gene and fused protein to examine the growth inhibition and cytodifferentiation induced by all-trans retinoic acid (ATRA), butyric acid (BA) and its prodrug tributyrin (TB) either as a single agent or in combinations. METHODS: NB4 and APL cells were cultured in presence of ATRA, BA and TB respectively either as a single agent or in combinations at various concentration ratio. Cell growth was measured and myeloid differentiation was determined by morphology and the percentage of positive nitroblue tetrazolium reduction (NBT) on consecutive days over the whole process of culture. RESULTS: NB4 cells can be induced by ATRA alone and synergistically induced by the combinations of BA or TB with ATRA to differentiate. The synergy was reflected by a remarkable decrease in the effective concentration of ATRA required in the combinations in comparison with it as a sole agent. The combinations also shortened the time for the cells to reach the same level of maturation as that needed for ATRA alone. The potentiation on ATRA-induced differentiation of NB4 cells seemed depending on an appropriate concentration ratio of each inducer in the combinations and the time of action. A preliminary result of in vitro induction of primarily cultured leukemic cells from APL patients by the combined inducers was promising. CONCLUSION: The combinations of ATRA with BA or TB at an appropriate ratio may improve the clinical outcome of differentiation therapy for APL patients.

Butyric Acid↗
PubMedDate not supplied

Butyric acid enhances in vivo expression of hTNF-alpha in transduced melanoma cell line.

Butyric acid (NaBut) and its derivatives are well-known agents eliciting tumor cell differentiation and apoptosis. In experimental models, NaBut is also used to enhance the efficacy of viral vectors. With the use of B78 murine melanoma cells transduced with the retroviral vector containing human tumor necrosis factor alpha (hTNF-alpha) gene, we investigated the ability of NaBut to increase the cytokine expression. We observed an increase in hTNF-alpha expression in vitro after incubation with NaBut. We also describe that the NaBut pro-drug tributyrin is able to increase hTNF-alpha expression in transduced B78 cells in a tumor vaccination model in mice. This observation strongly suggests a novel potential role for NaBut and its derivatives in tumor therapy. It could be used not only as a therapeutic directly acting on tumor cells but, in parallel, as a genetic vaccine "enhancer".

Animals↗
PubMed2002

Augmentation of sodium butyrate-induced apoptosis by phosphatidylinositol 3'-kinase inhibition in the KM20 human colon cancer cell line.

PURPOSE: We have recently shown that inhibition of the phosphatidylinositol3'-kinase (PI3k) pathway enhances sodium butyrate (NaBT)-mediated differentiation of human colon cancer cells. The purpose of this study was to determine whether PI3k inhibition can enhance the inhibitory effect of NaBT on an aggressive human colon cancer cell line, KM20. EXPERIMENTAL DESIGN: The KM20 cell line, established from a metastatic colon cancer, was treated in vitro with NaBT, gemcitabine, or 5-fluorouracil either alone or in combination with the PI3k inhibitors wortmannin or LY294002; DNA fragmentation and cell viability were measured. As further indicators of apoptosis, protein was extracted to determine caspase-9 and caspase-3 activation and cleavage of poly(ADP-ribose) polymerase. In addition, the effect of NaBT and wortmannin on in vivo KM20 tumor growth was determined. RESULTS: We demonstrate that inhibition of PI3k enhanced NaBT-mediated apoptosis and decreased KM20 cell viability; the nonspecific caspase inhibitor zVAD-fmk blocked the induction of apoptosis by the combination treatment. Either wortmannin or LY294002, combined with NaBT, enhanced activation of caspase-9 and caspase-3 and the subsequent cleavage of poly(ADP-ribose) polymerase. Furthermore, inhibition of PI3k increased the sensitivity of KM20 cells to gemcitabine and 5-fluorouracil. Wortmannin alone inhibited KM20 xenograft growth in vivo; the combination of wortmannin and NaBT demonstrated an enhanced effect compared with either agent alone. CONCLUSIONS: Our results are the first to show that inhibition of PI3k enhances NaBT-mediated colon cancer cell apoptosis through the activation of caspase-9 and caspase-3. Moreover, these findings suggest that agents that selectively target the PI3k pathway may enhance the effects of standard chemotherapeutic agents and provide novel adjuvant treatment for selected colon cancers.

Animals↗
PubMed2002

Changes in the cellular behaviour of human colonic cell line Caco-2 in response to butyrate treatment.

Gut-derived adenocarcinoma Caco-2 cells were treated with sodium butyrate (NaB) at physiologically relevant concentrations. We characterized its effects on proliferation, differentiation, apoptosis, adhesion to the solid support and interleukin-8 secretion. Differentiation was determined by brush border alkaline phosphatase activity. Apoptosis was assessed by acridine orange and Hoechst stains. Differentiation and apoptosis were analyzed in both adherent and floating cell populations. The transformed Caco-2 cells did not retain their malignant phenotype in the presence of NaB. They appeared to undergo a change in the phenotype induced by NaB, as indicated by reduced proliferation, enhanced differentiation, stimulation of apoptosis leading to decreased viability of cells, and stimulation of interleukin-8 secretion. Considering all the above facts and data, we postulate that Caco-2 cells cultured in NaB supplemented medium could regain the phenotypic characteristics of the phenotype of the parent cell from which originated the Caco-2 line.

Alkaline Phosphatase↗
PubMed2002

Molecular mechanism of enhanced apoptotic response in U937 cells mediated by sodium butyrate.

OBJECTIVE: To study the effects of sodium butyrate (NaBu) on cell cycle checkpoint and the apoptosis sensitivity in U937 cells. METHODS: Two mutant U937 cell lines, U937-ASPI3K (ATM negative) and U937-pZeosv2(+) (ATM wild-type), were used as the cell model system. Immunoprecipitation and kinase assay were used to examine the p38 MAPK and ERK1 kinase activities. Western blot was used to analyze the phosphorylation of Bad protein. RESULTS: U937-pZeosv2(+) pretreated with NaBu exhibited enhanced apoptotic response in a NaBu dose dependent fashion upon (137)Cs irradiation, which could be abolished by olomoucine (OLM), a p38 MAPK specific inhibitor. On the other hand, Cyclin dependent kinase 2 (CDK2) specific inhibitor CDK2-I and p34cdc2/cyclinB inhibitor alsterpaullone (ALP) failed to block the effects of NaBu. Similar results were also observed in U937-ASPI3K. The effect of irradiation on p38 MAPK and ERK1 was strikingly potentiated by NaBu. Furthermore, inactivation of irradiated Bad protein via phosphorylation on serine 136 was also enhanced. CONCLUSION: NaBu is able to enhance the apoptotic response in U937 cells, which is mediated by p38 MAPK activation but not ATM status.

Apoptosis↗
PubMed2002

Re-expression of p16 gene in the myeloma cell line U266 induced by synergy of sodium butyrate and 5-Aza-2'-deoxycytidine.

OBJECTIVE: To understand the synergic effect of histone deacetylase inhibitor sodium butyrate (SB) and demethylating agent 5-Aza-2'- deoxycytidine (5-Aza-CdR) on cell growth and to explore the possibility of re-expression of the hypermethylated and silenced p16 gene in the myeloma cell line U266. METHODS: U266 cells were cultured in RPMI 1640 in the presence of varied doses of SB and 5-Aza-CdR, and the growth curve was obtained by trypan-blue exclusion assay and cell count. The cell cycle was analyzed by flow cytometry and the expression level of mRNA and protein of p16 gene were detected by reverse transcriptase-PCR and Western blotting, respectively. RESULTS: The cell growth was arrested by treatment with 5-Aza-CdR alone or SB alone. Increased inhibition effect was shown in synergic treatment of SB and 5-Aza-CdR. The G(1) phase of cell cycle was arrested by 5-Aza-CdR combined with SB, which, however, did not occur when SB or 5-Aza-CdR was used alone. 5-Aza-CdR alone induced the expression of p16 gene in a concentration-dependent manner, whereas SB alone only induced its low-level expression. The expression level of both mRNA and protein of p16 gene was increased significantly by synergic application of SB and 5-Aza-CdR. CONCLUSION: Hypermethylated and silenced p16 gene in U266 cell line can be markedly reactivated by synergic treatment with demethylating agent 5-Aza-CdR and histone deacetylase inhibitor SB, and the cell growth can be inhibited and cell cycle arrested at G(1) phase.

Antimetabolites, Antineoplastic↗
PubMed2002

[Preliminary study of sodium butyrate-induced expression of lung resistance-related protein in K562 cells].

OBJECTIVE: To investigate the effect of sodium butyrate (NaB) on the expression level of lung resistance-related protein (LRP) in K562 cells. METHODS: K562 cells, used as an in vitro model system, were treated with NaB to induce differentiation of the cells. LRP mRNA expression and protein levels in the cells were detected by reverse transcriptase-PCR (RT-PCR) and flow cytometry, respectively. RESULTS: A 1-day treatment with 2 mmol/L NaB induced the gene expression of LRP to increase to the maximum in the cells, and a 3-day treatment caused the corresponding protein level to increase to the maximum. CONCLUSION: Both the mRNA level and the protein expression of LRP can be induced by NaB in K562 cells.

Butyrates↗
PubMed2002

The cyclin-dependent kinase inhibitor flavopiridol disrupts sodium butyrate-induced p21WAF1/CIP1 expression and maturation while reciprocally potentiating apoptosis in human leukemia cells.

Interactions between the cyclin-dependent kinase inhibitor flavopiridol (FP) and the histone deacetylase inhibitor sodium butyrate (SB) have been examined in human leukemia cells (U937) in relation to differentiation and apoptosis. Whereas 1 mM of SB or 100 nM of FP minimally induced apoptosis (4% and 10%, respectively) at 24 h, simultaneous exposure of U937 cells to these agents dramatically increased cell death (e.g., approximately 60%), reflected by both morphological and Annexin/propidium iodide-staining features, procaspase 3 activation, and poly(ADP-ribose) polymerase cleavage. Similar interactions were observed in human promyelocytic (HL-60), B-lymphoblastic (Raji), and T-lymphoblastic (Jurkat) leukemia cells. Coadministration of FP opposed SB-mediated accumulation of cells in G0G1 and differentiation, reflected by reduced CD11b expression, but instead dramatically increased procaspase-3, procaspase-8, Bid, and poly(ADP-ribose) polymerase cleavage, as well as mitochondrial damage (e.g., loss of mitochondrial membrane potential and cytochrome c release). FP also blocked SB-related p21WAF1-CIP1 induction through a caspase-independent mechanism and triggered the caspase-mediated cleavage of p27KIP1 and retinoblastoma protein. The latter event was accompanied by a marked reduction in retinoblastoma protein/E2F1 complex formation. However, FP did not modify the extent of SB-associated acetylation of histones H3 and H4. Treatment of cells with FP/SB also resulted in the caspase-mediated cleavage of Bcl-2 and caspase-independent down-regulation of Mcl-1. Levels of cyclins A, D1, and E, and X-linked inhibitor of apoptosis also declined in SB/FP-treated cells. Finally, FP/SB coexposure potently induced apoptosis in two primary acute myelogenous leukemia samples. Together, these findings demonstrate that FP, when combined with SB, induces multiple perturbations in cell cycle and apoptosis regulatory proteins, which oppose leukemic cell differentiation but instead promote mitochondrial damage and apoptosis.

Apoptosis↗
PubMed2002

Effects of sodium butyrate and acidic fibroblast growth factor on TDC32300 cultured cells.

BACKGROUND: Many studies have demonstrated that transition duct cells (TDC) are facultative liver stem cells. Our laboratory established TDC32300 cell lines with hepatic progenitor markers. The authors proposed that cell culture using sodium butyrate (NaBut) and acidic fibroblast growth factors (aFGF) may support the differentiation of TDC32300 cells along the hepatic lineage. METHODS: TDC32300 cells were cultured in four different conditions 1) STON media alone; 2) STON with NaBut in 3 different concentrations, 1 mM, 3.75 mM and 5 mM; 3) STON with aFGF; and 4) STON with aFGF and dexamethasone. After day 5, the cultured cells were fixed and stained with monoclonal antibodies to rat liver antigens and anti-proliferating nuclear antigen (PCNA). RESULTS: Proliferation of TDC32300 cells cultured in the high concentration of NaBut (3.75 and 5 mM) was inhibited. This phenomenon was confirmed by the reduction in cell number and decrease in PCNA expression. Irrespective of the concentration, NaBut did not alter the phenotype of the TDC32300 cultured cells. aFGF with or without dexamethasone also did not alter the phenotypic characteristic of TDC32300 cells. CONCLUSION: TDC32300 cells may not be the hepatic progenitors or that their differentiation may require other culture conditions.

Butyrates↗
PubMedDate not supplied

Morphology and intermediate filament composition of human mammary epithelial cells treated with stable butyrate derivative.

A new stable butyrate derivative monobut-3 was previously shown to inhibit proliferation and promote differentiation in human mammary established cell lines. The present study on monobut-3's effects on mammary epithelial cells cultured from human non-malignant and malignant breast tissues demonstrated pronounced morphological alterations suggestive of cellular differentiation. In addition, some degree of architectural differentiation was also evident in treated primary cultures. Monobut-3 did not affect the expression of vimentin and cytokeratin 18 when assessed in human breast cell lines expressing one or both types of intermediate filaments. However, it did induce expression of cytokeratin 19, characteristic of fully differentiated mammary cells, in one of the two cell lines devoid of this cytokeratin subtype. Furthermore, the network of intermediate filaments was often more largely extended in cells treated with monobut-3 than in untreated ones. These results indicate that monobut-3 can induce subtle changes in intermediate filaments which may contribute to its ability to promote differentiation in human mammary cells.

Antineoplastic Agents↗
PubMed2003

[Sodium butyrate-induced expression of lung resistance-related gene in human myeloid leukemia K562 cells].

BACKGROUND & OBJECTIVE: Overexpression of lung resistance-related protein(LRP) is involved in multidrug resistance and poor outcome in acute leukemia. This study was designed to investigate the effect of sodium butyrate (NaB) on LRP expression level and the function of LRP in K562 cells. METHODS: Human myeloid leukemia K562 cells, used as an in vitro model, were treated with NaB. The LRP mRNA expression and protein levels in the cells before and after NaB treatment were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry indirect immunofluorescence method,respectively. Intracellular Adriamycin(ADM) location and intracellular daunorubicin(DNR) accumulation were detected by fluorescence microscope and flow cytometry, respectively. RESULTS: Compared with untreated K562 cells, the LRP mRNA level in the cells treated with 2 mmol/L NaB was increased obviously; the protein expression were turned from negative result to positive result and the ratios of positive cells were increased from 1.68% to 35.81%. Intracellular DNR accumulation was decreased in the treated K562 cells and the mean fluorescence of DNR reduced 68.64% compared with the untreated K562 cells. There was strong ADM fluorescence in the nuclei of untreated K562 cells; while the treated K562 cells showed significantly less ADM fluorescence in their nuclei but more fluorescence in the cytoplasm. CONCLUSION: Both the mRNA level and the protein expression of LRP in K562 cells can be increased by NaB induction. LRP induced by NaB is involved in the decreasing anti-cancer drug accumulation and transporting the drugs from the nucleus to the cytoplasm in K562 cells.

Butyrates↗