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PubMed1996

Comparative effects of flavonoids on the growth, viability and metabolism of a colonic adenocarcinoma cell line (HT29 cells).

The aim of the present study was to compare the effect of five structural classes of flavonoids on the viability and metabolism of a colonic adenocarcinoma cell line (HT29 cells). The most prominent structural features of flavonoids favoring both their cytotoxic activity and their capacity to inhibit lactate release appear to be the desaturation of the 2, 3 bond and the position of attachment of the B ring. Indeed, flavonol and flavone are the most potent and, in both classes, the order of potency can be modulated by hydroxyl or methoxyl substituents. On the other hand, in our model, we did not find any correlation between flavonoid structure and their capacity to modulate cAMP level. This last point is discussed.

Adenocarcinoma↗

PubMed2000

Induction of protein kinase Czeta-related protein kinase by growth suppression in carcinogen-initiated epidermal cell-line WYF31 cells.

In primary cultured mouse epidermal cells, protein kinase C isozyme zeta (PKCzeta) consists of multiple forms, for example, low-salt eluted PKCzeta (1-PKCzeta; 79 and 85 kDa) and high-salt eluted PKCzeta (h-PKCzeta; 79 and 85 kDa) on anion-exchange column chromatography. In this study, biochemical and biophysical differences between 1-PKCzeta and h-PKCzeta were examined by using carcinogen-initiated mouse epidermal cell-line WYF31 cells, whose growth is stimulated by tumour promoter phorbol 12-myristate 13-acetate (PMA). The binding efficiency of h-PKCzeta to anti-PKCzeta antibody-affinity column was 10 times higher than that of 1-PKCzeta. T7-tagged rat PKCzeta overexpressed in WYF31 cells was recovered only in the high-salt eluted area on the anion-exchange column. Furthermore, when rat PKCzeta was stably overexpressed in WYF31 cells, the content of h-PKCzeta increased 4 to 5 times compared to that of parental cells, but the content of 1-PKCzeta was not altered. All of these results indicate that h-PKCzeta is the product of the PKCzeta gene (referred to as PKCzeta) and that 1-PKCzeta is closely related but different from PKCzeta (referred to as PKCzeta-related kinase). Interestingly, serum starvation of WYF31 cells caused a marked increase of the content of PKCzeta-related kinase with a concomitant decrease of PKCzeta content. These changes were reversed by stimulating the cell growth with 10% foetal calf serum. Prolonged treatment of starved cells with PMA, which induces the proliferation of WYF31 cells, also caused the downregulation of PKCzeta-related kinase. These results suggest that the expression levels of PKCzeta-related kinase and PKCzeta are differently regulated, and that the increased expression of PKCzeta-related kinase might play a significant role in the growth-suppression processes of WYF31 cells.

Amino Acid Sequence↗

PubMed2003

A major constituent of green tea, EGCG, inhibits the growth of a human cervical cancer cell line, CaSki cells, through apoptosis, G(1) arrest, and regulation of gene expression.

A constituent of green tea, (-)-epigallocatechin-3-gallate (EGCG) has been known to possess antiproliferative properties. In this study, we investigated the anticancer effects of EGCG in human papillomavirus (HPV)-16 associated cervical cancer cell line, CaSki cells. The growth inhibitory mechanism(s) and regulation of gene expression by EGCG were also evaluated. EGCG showed growth inhibitory effects in CaSki cells in a dose-dependent fashion, with an inhibitory dose (ID)(50) of approximately 35 microM. When CaSki cells were further tested for EGCG-induced apoptosis, apoptotic cells were significantly observed after 24 h at 100 microM EGCG. In contrast, an insignificant induction of apoptotic cells was observed at 35 microM EGCG. However, cell cycles at the G1 phase were arrested at 35 microM EGCG, suggesting that cell cycle arrests might precede apoptosis. When CaSki cells were tested for their gene expression using 384 cDNA microarray, an alteration in the gene expression was observed by EGCG treatment. EGCG downregulated the expression of 16 genes over time more than twofold. In contrast, EGCG upregulated the expression of four genes more than twofold, suggesting a possible gene regulatory role of EGCG. This data supports that EGCG can inhibit cervical cancer cell growth through induction of apoptosis and cell cycle arrest as well as regulation of gene expression in vitro. Furthermore, in vivo antitumor effects of EGCG were also observed. Thus, EGCG likely provides an additional option for a new and potential drug approach for cervical cancer patients.

Animals↗

PubMed2002

Peripheral blood mononuclear cells in early pregnancy promote invasion of human choriocarcinoma cell line, BeWo cells.

BACKGROUND: During the establishment of the maternal blood circulation around the implanting human embryo, maternal peripheral blood mononuclear cells (PBMC) directly contact trophoblasts. To determine the physiological significance of this interaction, the effects of PBMC obtained from pregnant women on the proliferative and invasive properties of a human choriocarcinoma cell line, BeWo cells, were examined. METHODS AND RESULTS: PBMC were obtained from women in early pregnancy and from women in the secretory phase of the menstrual cycle. PBMC from pregnant women significantly increased the number of invading BeWo cells in an invasion assay without affecting the proliferation of BeWo cells (P +/- 0.05). No significant changes were observed in the co-cultures with PBMC from non-pregnant women. The addition of conditioned medium, which was prepared by 2 days of incubation with PBMC from pregnant women, also enhanced BeWo cell invasion in a dose-dependent manner. Moreover, when PBMC obtained from non-pregnant women were incubated with recombinant HCG (0-10 IU/ml) for 2 days, significant augmentation of the effect on BeWo cell invasion was observed in the conditioned medium from HCG-treated PBMC (P +/- 0.05). CONCLUSION: This study indicated that soluble factor(s) secreted from PBMC promote BeWo cell invasion. It also showed the possible involvement of HCG in the regulation of BeWo cell invasion by PBMC. These findings suggest crosstalk between maternal PBMC and trophoblasts via soluble factor(s), which may play an important role in early embryo implantation.

Antibodies, Monoclonal↗

PubMed1999

The protein phosphatase inhibitors, okadaic acid and calyculin A, induce apoptosis in human submandibular gland ductal cell line HSG cells.

OBJECTIVE: To investigate a possible relationship between protein phosphorylation or dephosphorylation status and apoptosis in salivary gland cells, we examined the effects of okadaic acid and calyculin A, the protein phosphatase inhibitors, on cultured human submandibular gland ductal cell line, HSG cells. METHODS: HSG cells at subconfluent stages were exposed to varying concentrations of okadaic acid or calyculin A. Apoptoses were analysed in HSG cells by phase-contrast microscopy, WST-1 cytotoxicity assay, Hoechst 33342 staining, and DNA ladder formation. RESULT: Both okadaic acid and calyculin A induced cell death in HSG cells in a dose-dependent fashion. Marked nuclear condensation and fragmentation of chromatin was observed in HSG cells. DNA ladder formation was also detected in HSG cells by treatment with okadaic acid or calyculin A. The induced DNA ladder formation was dose-dependent with maximal effect at concentrations of 50 nM okadaic acid and 2 nM calyculin A, respectively, and were time-dependent from 14 h to 48 h. To further determine if new gene transcription and protein synthesis regulate okadaic acid-induced apoptosis in HSG cells, the cells were treated with cycloheximide or actinomycin D in the presence of 20 nM okadaic acid. Neither inhibitor protected the cells against okadaic acid-induced apoptosis. CONCLUSION: Based on the known selectivity of okadaic acid and calyculin A, our results indicate that the pathway of the apoptosis in the cultured salivary gland cells is regulated by protein phosphatase type 1 or type 2A. Our results also suggest that new protein synthesis and/or mRNA expression are not involved in okadaic acid-induced apoptosis in HSG cells.

Apoptosis↗

PubMed2002

[Experimental study on adenovirus-mediated transfer of p53 or adenovirus- mediated transfer of p53 combined with radiotherapy for human cervical cancer cell line HeLa cells].

OBJECTIVE: To evaluate the therapeutic efficiency of adenovirus-mediated transfer of p53(Ad-p53) or Ad-p53 combined with radiotherapy for human cervical cancer cell line HeLa cells. METHODS: HeLa cells were either transfected with Ad-p53 alone or with Ad-p53 combining with radiotherapy. Reverse transcription polymerase chain reaction(RT-PCR), the cell growth, morphological changes, cell cycle, apoptosis and molecular changes were measured using cell counting, microscopy, flow cytometry, DNA ladder, and in vivo therapy experiments to evaluate the therapeutic efficiency of the regimens. RESULTS: Ad-p53 could be transfected into HeLa cells and p53 mRNA could be expressed more in the targeted HeLa cells. Ad-p53 transfer had strong therapeutic effects to HeLa cells in vitro and in vivo (the inhibition rates were 61.8% and 54.8%, respectively), moreover, the combined administration of Ad-p53 and radiotherapy had stronger therapeutic effects in vitro and in vivo (the inhibition rate was 85.5% in vitro, and the inhibition rate was 77.4% in vivo). The inhibition rate by radiotherapy alone was 44.6% in vitro and 58.4% in vivo. Massive apoptosis of HeLa cells was induced by these regimens. Cell cycle analysis demonstrated that all these regimens could arrested HeLa cells in G(2)-M. CONCLUSIONS: After introduced into HeLa cells, Ad-p53 shows therapeutic efficiency for HeLa cells both in vitro and in vivo. Moreover, Ad-p53 could enhance therapeutic efficiency for HeLa cells when combined with radiotherapy.

Adenoviridae↗

PubMed1999

[lnhibition of arsenic trioxide on human tongue cancer cell line Tca8113 cells in Scid mice in vivo]

OBJECTIVE:To explore the antitumor effect of As(2)O(3) in Scid mice.METHODS:Human tongue cancer cell line Tca8113 cells were transp lanted to the subcutaneous tissues of Scid mice to produce tumors.The tumor inhibition rate (TIR) of As(2)O(3) was observed in Scid mice. RESULTS:The TIR of As(2)O(3) was 49.16%,Cytomorphologic study showed that arsenic trioxide induced apoptosis of Tca8113 cells.CONCLUSION: As(2)O(3) may have a good treating effect on oral squamous cell carcinoma.

Journal Article↗

PubMed2005

[Leukemic bone marrow stromal cells in vitro protect leukemic cell line Jurkat cells from daunorubicin-induced apoptosis].

BACKGROUND & OBJECTIVE: Tumor microenvironment affects tumor cells growth. Bone marrow microenvironment may protect leukemic cells from drug-induced damages, but the mechanism is unclear. This study was to explore the protection of bone marrow stromal cells (BMSCs) on leukemic cells against chemotherapy and its mechanism. METHODS: Normal and leukemic BMSCs were isolated using Percoll, and cocultured with human acute lymphocyte leukemic cell line Jurkat cells in vitro. After treatment of 0.5 micromol/L of daunorubicin (DNR), apoptosis and cell cycle distribution of Jurkat cells were analyzed by flow cytometry. RESULTS: When treated with DNR for 24 h, apoptosis rate of normal BMSCs-cocultured Jurkat cells was significantly lower than that of Jurkat cells without coculture [(8.39+/-4.08)% vs. (16.02+/-1.00)%, P < 0.05], and apoptosis rate of leukemic BMSCs-cocultured Jurkat cells was significantly lower than that of normal BMSCs-cocultured Jurkat cells [(5.73+/-1.78)% vs. (8.39+/-4.08)%, P < 0.05]; G(0)/G(1) phase percentage of BMSCs-cocultured Jurkat cells was significantly higher than that of Jurkat cells without coculture (P < 0.05), but the difference between Jurkat cells cocultured with normal and leukemic BMSCs was not significant (P > 0.05). CONCLUSION: Leukemic BMSCs may inhibit DNR-induced apoptosis in leukemic cells partly through G(0)/G(1) phase arrest.

Adolescent↗

PubMed1980

Properties of two temperature-sensitive Rous sarcoma virus transformed cerebellar cell lines.

Cells from the cerebellum of 3-day-old BD-IX rats were obtained as permanent lines by transforming them with temperature-sensitive Rous sarcoma virus. The presence or absence of veratridine-stimulated Na+-uptake (voltage-dependent channels) was used to operationally classify them as neuronal or glial. When incubated at 34 degrees C, the permissive temperature for transformation, the cerebellar cells exhibit a transformed phenotype determined by anchorage independence, rounded morphology, high growth rate and absence of density-dependent inhibition of growth. In contrast, when the transformed cerebellar cell lines are kept at a temperature (38 degrees C) non-permissive for transformation, they exhibit a normal cellular phenotype with respect to the above properties. Moreover, changes toward neuronal morphology, increase in veratridine-stimulated Na+-uptake, decreased growth rate and the expression of the astrocyte specific protein, glial fibrillary acidic protein, suggest that a degree of differentiation is expressed at the non-permissive temperature.

Animals↗

PubMed1997

Normal telomere maintenance in immortal ataxia telangiectasia cell lines.

Telomeres are maintained in germ line cells and immortal cell lines, but shorten with each cell division in most somatic cells. Blood lymphocytes from individuals with ataxia telangiectasia (AT) demonstrate an accelerated rate of telomere shortening and high levels of telomere associations. This accelerated loss of telomeres in somatic cells in AT could be due to either the loss of more telomeric DNA with every cell division or an increased rate of cell division. The gene for AT shares homology with the yeast TEL1 gene, in which mutations result in abnormally shortened telomeres. Thus, mutations in the gene for ataxia telangiectasia may also influence the ability of germ line cells and immortal cell lines to properly maintain telomere homeostasis. To investigate a possible defect of telomere maintenance in AT we have analyzed 8 simian virus 40 (SV40)-immortalized AT cell lines and twelve SV40-immortalized non-AT cell lines for both telomerase activity and telomere length. The results demonstrate that telomere length in AT cells is maintained via telomerase or an alternative (ALT) pathway in a manner indistinguishable from cell lines derived from normal cells. We also investigated telomere dynamics in one telomerase-positive AT cell line by analyzing the changes in the length of a single telomere, and found that this telomere maintained its equilibrium mean length (EML) similar to normal cell lines with stable chromosomes. The combined results show no significant differences between the telomeres of immortal AT and non-AT cell lines, demonstrating that the absence of wild-type ATM does not result in a fundamental defect in telomere maintenance in these cells.

Ataxia Telangiectasia↗

PubMed1998

Induced p53 expression in lung cancer cell line promotes cell senescence and differentially modifies the cytotoxicity of anti-cancer drugs.

The p53-null human lung cancer cell line H1299 was used in order to generate clones with ecdysone-inducible p53 as well as ecdysone-inducible p21waf1. Induced expression of p53 resulted in irreversible cell growth arrest with characteristics of replicative senescence, suggesting that p53 can prevent immortalization by activating a senescence program. The effect of induced p53 and p21waf1 expression on the cytotoxic action of the anti-cancer drugs etoposide and cisplatin was also analysed. Whereas p21waf1 overexpression conferred increased resistance to killing by either drug, p53 overexpression enhanced the cytotoxic effect of cisplatin but protected against etoposide cytotoxicity. These results imply that the impact of p53 on susceptibility to chemotherapy may depend greatly on the particular drug and type of DNA damage. Moreover, these data demonstrate the importance of using isogenic cell lines to address this issue.

Antineoplastic Agents↗

PubMed1987

Activation and growth of colony-stimulating factor-dependent cell lines is cell cycle stage dependent.

Hematopoietic cell development is regulated by a series of growth factors that are progressively restricted in their biological activity. IL-3 is a multi-lineage growth factor that supports the growth and differentiation of progenitor cells belonging to multiple lineages. However, the mechanism by which IL-3 induces proliferation and differentiation of these cells is not completely understood. In this report, we have used two IL-3-dependent cell lines, FDC-P1 (a myeloid progenitor) and F15.12 (a lymphoid progenitor) to investigate IL-3-mediated growth and differentiation. When either FDC-P1 or FL5.12 cells are deprived of IL-3, greater than 90% of all cells accumulate in the G0 phase of the cell cycle. Upon readdition of IL-3, the cells will reenter the active phases of the cell cycle. Therefore, IL-3 can act as both a competence (G0----G1) factor, and a progression (G1----M) factor for hematopoietic precursor clones. FDC-P1 cells can also proliferate in response to granulocyte/macrophage colony-stimulating factor (G/M-CSF) and IL-4 (B cell stimulatory factor 1 [BSF-1]). However, resting (G0) FDC-P1 cells have lost their ability to grow in response to both G/M-CSF and IL-4, even though both factors can induce a G0----G1 transition. Therefore, G/M-CSF or IL-4 behave as progression factors among certain IL-3-responsive clones, and in those cases only in defined points in the cell cycle. Both IL-4 and G/M-CSF can maintain long-term growth of FDC-P1 cells. Upon removal of factor for 24 h, these clones accumulate in the G1 phase of the cell cycle and do not appear to enter G0 even after 36 h of factor deprivation. Therefore, cells maintained in G/M-CSF or IL-4 have altered growth requirements compared with the IL-3-dependent lines from which they were derived. The ability of various hematopoietic growth factors to regulate cell cycle progression in IL-3-dependent cell lines is dependent not only upon the lineage from which these cells were derived, but also the phase of the cell cycle in which those cells reside. The consequences of these interactions dictate the manner by which various clones will respond to CSFs and whether the cells will grow and/or differentiate.

B-Lymphocytes↗

PubMed2002

15-Deoxy-delta12,14-prostaglandin J2 induces apoptosis of a thyroid papillary cancer cell line (CG3 cells) through increasing intracellular iron and oxidative stress.

Treatment of carcinoma cell lines with 15-deoxy-delta12,14-prostaglandin J2 (15d-PGJ2), a natural ligand of the peroxisome proliferator-activated receptor-gamma, has been reported to induce apoptosis and/or inhibit proliferation. In this study, we investigated the cytotoxic effect and the action mechanisms of 15d-PGJ2 in a thyroid papillary cancer cell line, CG3. The results indicate that 15d-PGJ2 caused cytotoxicity and increased the amount of intracellular reactive oxygen species (ROS) in these cells. Mitochondrial oxidative phosphorylation inhibitors (carbonyl cyanide m-chloro-phenylhydrazone, oligomycin, cyclosporin A and rotenone), NADPH oxidase inhibitor (diphenyleneiodonium), xanthine oxidase inhibitor (allopurinol) and NO synthase inhibitor (N-monomethyl-L-arginine acetate) did not reduce the generation of ROS. However, catalase, N-acetyl-cysteine and the iron chelator desferri-oxamine decreased the intracellular ROS of 15d-PGJ2-treated CG3 cells. Furthermore, 15d-PGJ2 enhanced the accumulation of iron in the CG3 cells. These data suggest that 15d-PGJ2 induces the generation of ROS by enhancing the accumulation of intracellular iron and that the increased oxidative stress may cause apoptosis of CG3 cells.

Apoptosis↗

PubMed1992

Deoxyadenosine toxicity in an adenosine deaminase-inhibited human CCRF-CEM T-lymphoblastoid cell line causes cell swelling.

The human T-lymphoblastoid cell line CCRF-CEM, pre-treated with 2'-deoxycoformycin, was used as a model for adenosine deaminase deficiency to investigate how 2'-deoxyadenosine exerts its cytotoxic effects. Incubation of these cells with 1 microM or 5 microM deoxyadenosine for 24 and 48 h caused an increase of up to 50% in their modal cell volume as measured by a Coulter Size Distribution Analyzer and this increase in cell volume was accompanied by an increase in their fragility and deformability. The swelling of cells was concomitant with the phosphorylation of deoxyadenosine and its intracellular accumulation as dATP. There was no evidence of osmotic imbalance or of inhibition of the Na+/K(+)-dependent ATPase activity as the intracellular concentrations (and the intracellular:extracellular ratios) of Na+, K+ and Ca2+ were essentially unchanged. Cytochalasin B (20 microM) also caused lymphoblasts to swell over a 6-h period and its effect on cell size was similar to that of either 1 microM or 5 microM deoxyadenosine over 24 or 48 h. Longer time-courses of incubation with cytochalasin B caused severe toxicity leading to the death and lysis of a significant proportion of the cells. Other drugs, such as colchicine, vincristine and vinblastine that are known to affect various components of the cytoskeleton also caused swelling of cells in a concentration- and time-dependent manner but there was no evidence that these effects were additive or synergistic with those of deoxyadenosine. Inhibition of DNA synthesis, either directly by aphidicolin or indirectly by hydroxyurea, was less cytotoxic than the effect caused by deoxyadenosine. We conclude that one of the toxic effects resulting from the excessive phosphorylation of deoxyadenosine and its accumulation as dATP in human T-lymphoblasts is not dependent on inhibition of DNA synthesis but may be caused by the disruption of the cytoskeleton in these cells.

Adenosine Deaminase↗

PubMed2002

Comparative in vitro sensitivities of human immune cell lines, vaginal and cervical epithelial cell lines, and primary cells to candidate microbicides nonoxynol 9, C31G, and sodium dodecyl sulfate.

In experiments to assess the in vitro impact of the candidate microbicides nonoxynol 9 (N-9), C31G, and sodium dodecyl sulfate (SDS) on human immune and epithelial cell viability, cell lines and primary cell populations of lymphocytic and monocytic origin were generally shown to be equally sensitive to exposures ranging from 10 min to 48 h. However, U-937 cells were more sensitive to N-9 and C31G after 48 h than were primary monocyte-derived macrophages. Cytokine activation of monocytes and lymphocytes had no effect on cell viability following exposure to these microbicidal compounds. Primary and passaged vaginal epithelial cultures and cell lines differed in sensitivity to N-9 and C31G but not SDS. These studies provide a foundation for in vitro experiments in which cell lines of human immune and epithelial origin can be used as suitable surrogates for primary cells to further investigate the effects of microbicides on cell metabolism, membrane composition, and integrity and the effects of cell type, proliferation, and differentiation on microbicide sensitivity.

Betaine↗

PubMed2004

In vitro effects of recombinant human growth hormone on growth of human gastric cancer cell line BGC823 cells.

AIM: To study the effects of recombinant human growth hormone (rhGH) on growth of human gastric cancer cell line in vitro. METHODS: Experiment was divided into control group, rhGH group, oxaliplatin (L-OHP) group and rhGH+L-OHP group. Cell inhibitory rate, cell cycle, cell proliferation index (PI) and DNA inhibitory rate of human gastric cancer line BGC823, at different concentrations of rhGH treatment were studied by cell culture, MTT assay and flow cytometry. RESULTS: The distinctly accelerated effects of rhGH on multiplication of BGC823 cell line were not found in vitro. There was no statistical significance between rhGH group and control group, or between rhGH+L-OHP group and L-OHP group (P>0.05). The cell growth curve did not rise. Cell inhibitory rate and cells arrested in G(0)-G(1) phase were obviously increased. Meanwhile, cells in S phase and PI were distinctly decreased and DNA inhibitory rate was obviously increased in rhGH+L-OHP group in comparison with control group and rhGH group, respectively (P<0.01). Cell inhibitory rate showed an increasing trend and PI showed a decreasing trend in rhGH+L-OHP group compared with L-OHP group. CONCLUSION: In vitro rhGH does not accelerate the multiplication of human gastric cancer cells. It may increase the therapeutic efficacy when it is used in combination with anticancer drugs.

Antineoplastic Agents↗

PubMed1992

IGF-II mRNA expression in LI human glioblastoma cell line parallels cell growth.

A human glioblastoma cell line was found to express in vitro mRNA transcripts specific for insulin-like growth factor-II (IGF-II) and growth-hormone releasing-hormone (GHRH). In the absence of gross morphological changes, retinoic acid reduced the growth rate without major change of IGF-II mRNA expression, while alpha-difluoromethylornithine produced a complete growth arrest and a sharp decrease of IGF-II mRNA expression. Both reagents increased the expression of GHRH mRNA. Also in this glioblastoma cell line, like other neuroectodermal tumours, IGF-II mRNA is expressed independently from GHRH and seems to be parallel to growth rate.

Blotting, Northern↗

PubMed1994

Limiting dilution analysis of a novel tripeptide anticancer agent Ambamustine (PTT-119): effect on K-562, CCRF-SB and multidrug resistant LoVo-Dk cell lines.

Cell suspensions of normal human bone marrow were mixed with human acute lymphoblastic or myelogenous leukemic cells of the CCRF-SB or K-562 lines. After incubating the cell mixtures in vitro with different dose levels of Ambamustine (PTT-119), a quantity of 10(4) treated cells were dispensed into microculture plates, and graded cell numbers of the lines used to contaminate the normal marrow were added. Limiting dilution analysis (LDA) was used to estimate the frequency of leukemic cells persisting after treatment. Incubation with 50 micrograms/mL of PTT-119 produced a total elimination of K-562 acute myelogenous blasts, whereas nearly 0.17 and 0.27 leukemic cells were still present in the cell mixtures after treatment with 5 and 25 micrograms/mL, respectively. When normal bone marrow was contaminated with CCRF-SB lymphoblastic cells, incubation with either 50 or 25 micrograms/mL of PTT-119 produced a complete clearing of leukemic cells, whereas with 5 micrograms/mL the leukemic cells in each well were 0.18. When PTT-119 was incubated with LoVo-DX, a colon cancer cell line which expresses the pleiotropic drug resistance MDR phenotype, virtually complete inhibition of clonogenic colonies was observed with as little as 5 micrograms/mL. This suggests that PTT-119 could be used in clinical trials as a non-cross-resistant agent in multidrug protocol.

Antineoplastic Agents↗