The induction of apoptosis is a common feature of the cytotoxic action of ether‐linked glycerophospholipids in human leukemic cells

Diomede, Luisa; Piovani, Bianca; Re, Fabio; Principe, Paola; Colotta, Francesco; Ej, Modest; Salmona, Mario

doi:10.1002/ijc.2910570506

Cited by 39 publications

(19 citation statements)

References 19 publications

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“…Testing a larger panel of agents, we have confirmed our earlier finding (Lohmeyer and Workman, 1992) (Munder and Westphal, 1990;Berdel, 1991) PI-3-kinase, the Na+/K+-ATPase, Ca2+ channels and the epidermal growth receptor (Oishi et al, 1988;Kosano and Takatani, 1989;Powis et al, 1992;Berggren et al, 1993 (Honma et al, 1981(Honma et al, , 1991Vallari et al, 1988;Maurer and Hilgard, 1992), but inhibition of differentiation has also been described in the same model system (Shoji et al, 1988;Kuo et al, 1990;Raynor et al, 1991). Apoptosis has been observed in some leukaemic cell lines, including HL60, in response to challenge with ATLs (Diomede et al, 1993(Diomede et al, , 1994, but this response is not universal (Morimoto et al, 1991). (3) As concentrations exceed 40 JAM, the detergent properties of the ATLs begin to induce direct lytic membrane damage.…”

Section: Discussionmentioning

confidence: 99%

Growth arrest vs direct cytotoxicity and the importance of molecular structure for the in vitro anti-tumour activity of ether lipids

Lohmeyer

Workman²

1995

Br J Cancer

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Summary A panel of 25 different lipid agents was evaluated for in vitro activity against HT29 human colon carcinoma and HL60 promyelocytic leukaemia cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The structure-activity relationships seen with this series, including those for four sets of positional or stereoisomers, indicate that specific receptor proteins are unlikely as targets for anti-tumour lipid (ATL) action. Additional data confirm the lack of involvement of the platelet-activating factor receptor in particular and suggest that metabolic stability is a most important determinant of ATL activity. More detailed studies, with 1-O-octadecyl-2-0-methyl-rac-glycero-3-phosphocholine (ET18-OCH3) and (±)-2-{Hydroxy[tetrahydro-2-(octadecyloxy)methylfuran-2-yl]methoxylphosphinyloxy)-N,N,N,-trimethylethaniminium hydroxide (SRI 62-834), suggest three different modes of activity, depending on drug concentration and exposure time. Low doses of up to 5 jiM in standard serum-containing medium cause population growth arrest after prolonged exposure. Growth arrest was associated with a leaky G2/M block as determined by flow cytometry. These effects are reversible. Intermediate concentrations (5-40 M) were cytotoxic, causing a net reduction in cell numbers after 2-3 days. At even higher concentrations, all lipids caused rapid, direct membrane lysis. When the clonogenic assay was used to assess the effects of ATLs, most agents reduced colony formation at concentrations above 5 jIM. However, some compounds proved stimulatory at nanomolar concentrations, suggesting that they might possess mitogenic properties. These results, particularly those concerning the concentration and time dependence, may be relevant to current clinical trials with ether lipids.

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Section: Discussionmentioning

confidence: 99%

Growth arrest vs direct cytotoxicity and the importance of molecular structure for the in vitro anti-tumour activity of ether lipids

Lohmeyer

Workman²

1995

Br J Cancer

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“…The pharmacological inducers included the ether lipids ALP and HePC, 25 the second messengers C 2 -ceramide 26 and the Ca ++ -mobilizing agent thapsigargin. 27 Figure 4 illustrates that H.2 cells were resistant to DEX but equally sensitive as wild-type S49 cells for the induction of characteristic G 2 delay and of hypodiploid cells by the cytostatic drug etoposide.…”

Section: Sensitivity To Pharmacological Inducersmentioning

confidence: 99%

Involvement of the glucocorticoid receptor in stress-induced apoptosis of leukemic cells

et al. 1998

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Glucocorticoid (GC) hormones induce apoptosis in lymphoid and leukemic cells by binding and activating cytosolic GC receptors. Because physiological stress often causes hormone-free GC receptor activation, we have investigated if stress-induced apoptosis of lymphoid cells is also mediated by the activation of the GC receptor pathway. In S49 T lymphoma cells, heat shock and deprivation of growth factors or nutrients caused nuclear translocation and loss of agonist binding capacity of GC receptors, similar to that in cells incubated with the glucocorticoid dexamethasone (DEX). In variant S49 H.2 cells, cross-resistance to DEX, temperature shocks and growth factor deprivation were associated with a higher threshold for hormone-dependent and -independent receptor activation in situ and with impaired in vitro activation of cytosolic receptors. Cross-resistance to DEX, low serum and heat shock was abrogated, however, by pharmacological sensitization of GC receptor activation with the drug meta-iodobenzylguanidine (MIBG). Sensitive S49 cells and resistant variants did not differ in the expression levels of the apoptosis-regulating genes bax, bad, bcl-X and bcl-2, the status of the p53 gene nor in a different requirement for the growth factors Il-2, IL-4 or IL-9. The results suggest that ligand-independent activation of the GC receptor is a central signalling and controlling event in some forms of stress-induced apoptosis, assigning a novel function to the GC receptor in the regulation of lymphoid and leukemic cell numbers.

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“…In fact we found by GC-MS a high content of alkylglycerol in the capsules offered to the supplemented animals (Table 2B). A study with leukemia patients supplemented with alkylglycerols reported an increased oxidative stress after the nutritional intervention, which the authors pointed as the mechanism behind the increased number of apoptotic neoplastic cells in such patients [14].…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported a time-and concentrationdependent development of oxidative stress when sensitive HL-60 cells were exposed to membrane-targeted ether lipids [13]. Oxidative stress has been suggested as an inducer of apoptosis in human leukemic cells [14]. Induction of oxidative stress followed by apoptosis is also assumed to explain the inhibition of L-1 sarcoma-induced angiogenesis by alkylglycerols [15].…”

Section: Introductionmentioning

confidence: 99%

Exercise and Shark Liver Oil Supplementation Reduce Tumor Growth and Cancer Cachexia in Walker 256 Tumor Bearing Rats

Bordignon¹

2014

J Cancer Sci Ther

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This study investigated whether exercise associated to shark liver oil supplementation (1 g/kg b.w./day) affects tumor growth, cachexia, lipid peroxidation and proteins expression involved in cell death in Walker 256 tumorbearing rats. Animals were divided into 4 groups: sedentary tumor-bearing (W), sedentary tumor-bearing shark liver oil supplemented (WSL), exercised tumor-bearing (EW) and exercised tumor-bearing shark liver oil supplemented (EWSL). Training sessions consisted of 6 bouts, 30 seconds each with 50% body-weight load attached to the trunk followed by 1 minute of resting (jump training). Five minutes after the finish jump training the exercise groups were subjected to 30 minutes of continuous swimming with a load equivalent to 6% of body weight, 4 times a week during 8 weeks. Tumor cells were injected at the 6 th training week and all groups were killed 15 days post inoculation. Tumor weight (g) in W group was of 26.50 ± 1.79 and in the WSL, EW and EWSL was of 14.08 ± 0.91, 15.60 ± 0.55 and 12.60 ± 1.07, respectively. The group W showed hypoglycemia (68.67 ± 2.12 mg/dl), hyperlactacidemia (1.49 ± 0.06 mmol/L), hypertriacylglycerolemia (161.4 ± 9.4 mg/dl) and body weight reduction (13.21 ± 2.25 g) characterizing cachexia state. The groups WSL, EW and EWSL presented reduction of tumor cells proliferation ex vivo, and the production of hydroperoxide and apoptosis was increased. Bax/Bcl-2 expression ratio was increased only in the exercised groups. Shark liver oil supplementation and exercise alone were able in to avoid the installation of cachexia state and also reduced tumor growth, but the association of both cause further effect only in the tumor growth.

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The induction of apoptosis is a common feature of the cytotoxic action of ether‐linked glycerophospholipids in human leukemic cells

Cited by 39 publications

References 19 publications

Growth arrest vs direct cytotoxicity and the importance of molecular structure for the in vitro anti-tumour activity of ether lipids

Growth arrest vs direct cytotoxicity and the importance of molecular structure for the in vitro anti-tumour activity of ether lipids

Involvement of the glucocorticoid receptor in stress-induced apoptosis of leukemic cells

Exercise and Shark Liver Oil Supplementation Reduce Tumor Growth and Cancer Cachexia in Walker 256 Tumor Bearing Rats

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