Caffeine induces a second wave of apoptosis after low dose-rate gamma radiation of HL-60 cells

Vávrová, Jiřina; Mareková-Rezácová, Martina; Vokurková, Doris; Szkanderová, Sylva; Psutka, Jan

doi:10.1007/s00411-003-0209-4

Cited by 19 publications

(14 citation statements)

References 18 publications

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“…It was reported by many studies that p53 lacking cells, including HL-60 cells, react to DNAdamaging factors (such as e.g. ionizing radiation or topoisomerase II inhibitors) preferentially by arrest of cell cycle in G2/M phase, which is followed by apoptosis induction (2,15,27,31,32,(36)(37)(38). This was not observed after 2-DG treatment, indicating that direct damage to DNA is not responsible for the antitumor effect of 2-DG.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Antineoplastic Activity of L-rhamnose in vitro. A Comparison with 2-deoxyglucose

Tomšík

Stoklasová

Mičuda

et al. 2008

Acta Med. (Hradec Kralove, Czech Repub.)

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IntroductionIn the last decades, the possible effects of unsubstituted deoxyhexoses on tumor cells and their use in cancer treatment have been discussed. Above all, 2-deoxy-D-glucose (2-DG) and L-fucose have been studied in numerous works both in vitro and in vivo. 2-Deoxyglucose is a synthetic glucose analogue that inhibits phospho-hexose isomerase in the initial stage of glycolysis (29,33) and induces glucoseregulated stress affecting tumor cells in particular (9, 42). The inhibitory effect of 2-DG on tumor growth has been reported in both in vitro (43) and in vivo (5, 10) studies. Glycolysis inhibition and resulting energy depletion trigger apoptotic cell death. The mechanisms include inhibition of phosphatidylinositol 3-kinase/Akt signaling (35), increased production of reactive oxygen species, interference with MAPK pathways and stabilization of p53 (19). Corresponding to this, 2-DG was found to induce cell death by the activation of apoptosis (1). Regardless of the mechanism which triggers apoptosis by either intrinsic (mitochondrial) or extrinsic (receptor) pathways, the apoptotic cells can be recognized by specific morphological changes: membrane blebbing, condensation, fragmentation of nuclear DNA, cleavage of nuclear proteins (e.g. lamin B) and formation of apoptotic bodies.L-fucose (6-deoxy-L-galactose) is the only endogenous deoxyhexose known in humans. Although a research group reported the effect of intravenously administered L-fucose on the size of a rat solid mammary adenocarcinoma in vivo (25, 41) as well as the efficacy of this deoxysugar in vitro (21,24,28,40), no significant cytostatic potency of single L-fucose in vitro or L-fucose monotherapy has been confirmed in the recent literature. However, it has been noted that L-fucose enhances the cytolytic activity of immune system effector cells and the production of cytokines like interleukin 2 and tumor necrosis factor α (30). It is well documented that altered fucosylation plays an important role in the pathogenesis of malignant tumors (3,11,12). A potential antimetastatic effect of L-fucose and L-fucose containing oligosaccharides was reported as well (26).In nature, there is another deoxyhexose -L-rhamnose (6-deoxy-L-mannose) -similar to deoxyglucose. It is synthesized largely in plants and bacteria but not in animal cells (7). Since L-rhamnose can serve as substrate for L-fucose kinase (8), which catalyzes the first step in the salvage pathway for GDP-fucose biosynthesis (3), a hypothesis can be formulated that L-rhamnose could influence the fucosylation and thereby the behavior of tumor cells. The fact that L-rhamnose can be converted into glycosides in mammalian cells has been indeed evidenced by sporadic discoveries of rhamnosides in mammals (14, 34). Moreover, L-rhamnose, which penetrates by non-mediated diffusion into the cells (4), may be partially metabolized or join some human metabolic pathways (6,13 Summary: The effect of unsubstituted deoxyhexoses, 2-deoxy-D-glucose (2-DG) and L-fucose, on tumor cells has been reported in several...

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Section: Discussionmentioning

confidence: 99%

Evaluation of the Antineoplastic Activity of L-rhamnose in vitro. A Comparison with 2-deoxyglucose

Tomšík

Stoklasová

Mičuda

et al. 2008

Acta Med. (Hradec Kralove, Czech Repub.)

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“…In another report, caffeine induced a second wave of apoptosis in irradiated HL-60 cells. 20 Jha et al 10 observed that the G2-phase delays were eliminated by caffeine in the tumor cell lines (HeLa, MCF7, OVGI), but in sharp contrast, caffeine did not eliminate or even reduce the gamma-ray-induced G2-phase delays in any of the human normal cell lines (GM2149, GM4626, AG1522). This was important for the radiosensitization effect of caffeine in clinical application because caffeine can enhance the radiosensitivity of the hepatocellular carcinoma cell and cannot cause the additional burden on the normal liver cell at the same time.…”

Section: Discussionmentioning

confidence: 96%

Caffeine Enhances MHCC97H Cell Line Radiosensitization by Shortening G2-Phase ArrestIn Vitro

Zhang

Zeng

Tang

2011

Journal of Caffeine Research

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Purposes: The purposes of this study were to determine whether caffeine enhances radiosensitivity in MHCC97H cells and elucidate the underlying mechanisms in vitro.Methods and Materials: MHCC97H cells, hepatocellular carcinoma cells with high metastatic potential carrying mutant p53, were incubated with and without 2.5 mM caffeine and irradiated using a linear accelerator with 6-MV photons, at a dose of 200 cGy/minute. The cytotoxic effect of caffeine on MHCC97H cell line was measured by the 3,4-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle distribution and apoptosis were observed by flow cytometry. Expression of phosphorylated CDC2 Tyr15 (CDC2-Tyr15-P) was investigated using western blotting. The cell clonogenic assay was used to assess the radiosensitization effect of caffeine.Results: The 50% inhibitory concentration of caffeine was 2.79 mM. At 48 hours after 16-Gy radiation, apoptosis was 19.4% with radiation alone and 32.3% with radiation and caffeine. The proportion of cells in G2/M-phase arrest increased as the radiation dose increased, with 13.9% at 0 Gy, 25.6% at 8 Gy, 41.4% at 16 Gy, and 51.6% at 24 Gy. After 16-Gy radiation, the proportion of cells in G2-phase arrest was 37.6% without caffeine and 29.6% with caffeine at 12 hours. Apoptosis increased greatly after the G2/M-phase arrest was released by caffeine. Phosphorylation of CDC2 Tyr15 increased when G2/M-phase arrest was induced by irradiation, but caffeine suppressed the expression of CDC2-Tyr15-P.Conclusions: Caffeine enhanced the radiosensitivity of MHCC97H hepatocellular carcinoma cells carrying mutant-type p53 mainly through the abrogation of radiation-induced G2/M-phase arrest by suppressing the phosphorylation of CDC2 Tyr15.

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“…In this study, D0-values obtained from the multi-target formalism fall within the range of those reported in in vitro and in vivo studies using cells originating from a wide variety of malignancies. 1,[28][29][30][31][32][33][34][35] Although there were changes in rank-order between D0-values obtained from the multi-target and linear-quadratic (LQ) formalisms, they did not significantly affect the variations of D0 within each group of cell lines ( Table 1). Specifically, the coefficients of variation in D0…”

Section: Discussionmentioning

confidence: 99%

“…With the exception of highly radiosensitive ataxia telangiectasia cells, typical D0-values for tumor and normal cells have been found to range between~0.9 and 3.7 Gy. 1,[28][29][30][31][32][33][34][35] To test the strength of our model for extrapolating radiosensitivity at doses for which in vitro experimental data cannot be generated, the data presented in larly derived from  and  parameters that were reported for glioblastoma, neuroblastoma, and prostate cell lines in other historic studies. [41][42][43][44] The comparison is shown in Figure 5 and illustrates that the current and historical data are congruent.…”

Section: Discussionmentioning

confidence: 99%

“…Determination of D0 from in vitro cell survival data, using either the LQ or the multi-target model, has typically been possible over the first 3 logs of cell kill giving D0 values of 1.0 -3.7 Gy. 1,[28][29][30][31][32][33][34][35] It is conceivable that values of D0 derived at higher levels of cell kill may differ markedly from those obtained in the first few logs of cell kill, and can have a significant impact on the magnitude of the -parameter. Hence, the role of D0 in determining the appropriateness of the LQ formalism in modeling radiation response in stereotactic radiotherapy needs further evaluation.…”

Section: Introductionmentioning

confidence: 99%

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Estimation of transition doses for human glioblastoma, neuroblastoma and prostate cell lines using the linear-quadratic formalism

Akudugu

Serafin

2015

Int J Cancer Ther Oncol

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Cite this article as: Akudugu J, Serafin A. Estimation of transition doses for human glioblastoma, neuroblastoma and prostate cell lines using the linear-quadratic formalism. Int J Cancer Ther Oncol 2015; 3(3):3311. Original ArticleAbstract Purpose: The introduction of stereotactic radiotherapy has raised concerns regarding the use of the linear-quadratic (LQ) model for predicting radiation response for large fractional doses. To partly address this issue, a transition dose D* below which the LQ model retains its predictive strength has been proposed. Estimates of D* which depends on the , β, and D0 parameters are much lower than fractional doses typically encountered in stereotactic radiotherapy. D0, often referred to as the final slope of the cell survival curve, is thought to be constant. In vitro cell survival curves generally extend over the first few logs of cell killing, where D0-values derived from the multi-target formalism may be overestimated and can lead to low transition doses. Methods: D0-values were calculated from first principles for each decade of cell killing, using experimentally-determined  and β parameters for 17 human glioblastoma, neuroblastoma, and prostate cell lines, and corresponding transition doses were derived. Results:D0 was found to decrease exponentially with cell killing. Using D0-values at cell surviving fractions of the order of 10 -10 yielded transition doses~3-fold higher than those obtained from D0-values obtained from conventional approaches. D* was found to increase from 7.84 ± 0.56, 8.91 ± 1.20, and 6.55 ± 0.91 Gy to 26.84 ± 2.83, 23.95 ± 2.03, and 22.49 ± 2.31 Gy for the glioblastoma, neuroblastoma, and prostate cell lines, respectively. Conclusion: These findings suggest that the linear-quadratic formalism might be valid for estimating the effect of stereotactic radiotherapy with fractional doses in excess of 20 Gy.D0-values derived from the multi-target formalism. FIG. 5: Plot of D0, derived from LQ parameters, against the decade of cell killing in which D0 is derived for human glioblastoma, neuroblastoma, and prostate cell lines. Symbols representing pooled data from Figures 2-4 are superimposed on fitted curves from historical data for glioblastoma (dotted line) 41 , neuroblastoma (dashed line) 31, 43 and prostate (solid line) 44 cell lines. Large symbols represent D0-values derived from the multi-target formalism from cell survival data for each group of cell lines. 36-38 Error bars represent the standard error of the mean for each set of pooled data.Similarly, D0 declined from 1.85 ± 0.38 to 0.68 ± 0.04 Gy in the neuroblastoma cell lines (Figure 3). For the prostate cell lines, D0 decreased from 2.28 ± 0.23 Gy at high levels of cell survival to 0.81 ± 0.08 Gy at high levels of cell killing (Figure 4). In all cases, D0-values derived from the multi-target formalism were significantly higher than those obtained from the LQ model at a cell survival level of 10 -10 (P  0.0023).The resulting transition doses obtained from D0-values derived from the LQ model were f...

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Caffeine induces a second wave of apoptosis after low dose-rate gamma radiation of HL-60 cells

Cited by 19 publications

References 18 publications

Evaluation of the Antineoplastic Activity of L-rhamnose in vitro. A Comparison with 2-deoxyglucose

Evaluation of the Antineoplastic Activity of L-rhamnose in vitro. A Comparison with 2-deoxyglucose

Caffeine Enhances MHCC97H Cell Line Radiosensitization by Shortening G2-Phase ArrestIn Vitro

Estimation of transition doses for human glioblastoma, neuroblastoma and prostate cell lines using the linear-quadratic formalism

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