scholarly journals Bcl-2 and Bcl-XL Can Differentially Block Chemotherapy-Induced Cell Death

Blood ◽  
1997 ◽  
Vol 90 (3) ◽  
pp. 1208-1216 ◽  
Author(s):  
Philip L. Simonian ◽  
Didier A.M. Grillot ◽  
Gabriel Nuñez
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Viability ◽  
Wide Spectrum ◽  
Present Report ◽  
Chemotherapeutic Agents ◽  
Cell Cycle Phase ◽  
Lymphoid Cells ◽  
Cycle Phase ◽  
Γ Irradiation

Abstract Bcl-2 and its homologue Bcl-XL are expressed in a variety of tumors and their expression modulates the sensitivity of tumor cells to a wide spectrum of chemotherapeutic agents and γ-irradiation. In the present report, we generated clones of FL5.12 lymphoid cells with similar levels of Bcl-2 and Bcl-XL using the Flag epitope to determine if these survival proteins could provide equivalent protection when challenged with chemotherapy or γ-irradiation. Using four M-phase specific chemotherapeutic agents, Bcl-XL and Bcl-2 provided similar protection against vincristine and vinblastine whereas Bcl-XL afforded as much as 50% greater cell viability than Bcl-2 against etoposide and teniposide-induced cell death. In addition, Bcl-XL provided significantly greater cell viability than Bcl-2 against methotrexate, fluorouracil, and hydroxyurea, three S-phase specific agents. In apoptosis induced by γ-irradiation and cisplatin, two antitumor treatments that are cell-cycle phase-nonspecific agents, both Bcl-XL and Bcl-2 conferred similar protection against γ-irradiation, but Bcl-XL provided better protection than Bcl-2 against cisplatin. These results indicate that Bcl-XL and Bcl-2 confer a differential ability to protect against chemotherapy-induced cell death, which appears to be dependent on the molecular mechanism targeted by the drug rather than its cell-cycle phase specificity.

scholarly journals Bcl-2 and Bcl-XL Can Differentially Block Chemotherapy-Induced Cell Death

Blood ◽  
1997 ◽  
Vol 90 (3) ◽  
pp. 1208-1216 ◽  
Author(s):  
Philip L. Simonian ◽  
Didier A.M. Grillot ◽  
Gabriel Nuñez
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Viability ◽  
Wide Spectrum ◽  
Present Report ◽  
Chemotherapeutic Agents ◽  
Cell Cycle Phase ◽  
Lymphoid Cells ◽  
Cycle Phase ◽  
Γ Irradiation

Bcl-2 and its homologue Bcl-XL are expressed in a variety of tumors and their expression modulates the sensitivity of tumor cells to a wide spectrum of chemotherapeutic agents and γ-irradiation. In the present report, we generated clones of FL5.12 lymphoid cells with similar levels of Bcl-2 and Bcl-XL using the Flag epitope to determine if these survival proteins could provide equivalent protection when challenged with chemotherapy or γ-irradiation. Using four M-phase specific chemotherapeutic agents, Bcl-XL and Bcl-2 provided similar protection against vincristine and vinblastine whereas Bcl-XL afforded as much as 50% greater cell viability than Bcl-2 against etoposide and teniposide-induced cell death. In addition, Bcl-XL provided significantly greater cell viability than Bcl-2 against methotrexate, fluorouracil, and hydroxyurea, three S-phase specific agents. In apoptosis induced by γ-irradiation and cisplatin, two antitumor treatments that are cell-cycle phase-nonspecific agents, both Bcl-XL and Bcl-2 conferred similar protection against γ-irradiation, but Bcl-XL provided better protection than Bcl-2 against cisplatin. These results indicate that Bcl-XL and Bcl-2 confer a differential ability to protect against chemotherapy-induced cell death, which appears to be dependent on the molecular mechanism targeted by the drug rather than its cell-cycle phase specificity.

scholarly journals Measurement of cell-cycle phase-specific cell death using Hoechst 33342 and propidium iodide: preservation by ethanol fixation.

1988 ◽  
Vol 36 (9) ◽  
pp. 1147-1152 ◽  
Author(s):  
G Ciancio ◽  
A Pollack ◽  
M A Taupier ◽  
N L Block ◽  
G L Irvin
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Propidium Iodide ◽  
Cell Cycle Phase ◽  
Cytotoxic Agents ◽  
Cycle Phase ◽  
Specific Cell ◽  
Dead Cell ◽  
Hoechst 33342 ◽  
The Dead

We developed a rapid technique for preservation of Hoechst 33342/propidium iodide-stained cells, using ethanol as a fixative. Combined staining with these dyes makes possible analysis of cell-cycle phase-specific cell death. The technique relies on exclusion of propidium iodide from the viable cells, whereas Hoechst stains all of the cells. The bivariate histograms resulting from the flow cytometric analysis contain the equivalent of two single-parameter DNA histograms, one of the living and the other of the dead cell population. Preservation of staining involved addition of 25% ethanol in PBS after propidium iodide staining and before Hoechst staining. The separation between the living and the dead cell populations was maintained for over 3 days at 4 degrees C. This technique will be valuable for quantitative evaluation of the cell-cycle phase-specific effects of cytostatic or cytotoxic agents, particularly in situations where a lag period between staining and analysis is unavoidable.

scholarly journals SEPARATION OF HUMAN LYMPHOID CELLS INTO G1, S, AND G2 CELL CYCLE POPULATIONS BY USE OF A VELOCITY SEDIMENTATION TECHNIQUE

1973 ◽  
Vol 137 (2) ◽  
pp. 343-358 ◽  
Author(s):  
Lloyd K. Everson ◽  
Donald N. Buell ◽  
G. Nicholas Rogentine
Keyword(s):  
Cell Cycle ◽  
Surface Membrane ◽  
Fold Increase ◽  
Growth Patterns ◽  
Cell Cycle Phase ◽  
Lymphoid Cells ◽  
Velocity Sedimentation ◽  
Cycle Phase ◽  
Growth Media ◽  
Human Lymphoid Cell

Human lymphoid tissue culture cells can be separated according to cell size and corresponding cell cycle phase with a velocity sedimentation centrifugation method employing a continuous 5–20% wt/wt Ficoll gradient. A 7-fold increase in streaming limit was achieved by placing a buffer zone of isosmolar 5% Ficoll on top of the gradient before application of the cell load. The various pooled populations of cells from upper, middle, and lower areas of the gradient were characterized using autoradiographic, TCA-precipitable 3H]thymidine incorporation, and Fuelgen microspectrophotometric methods. The upper range of the gradient contains cells in the G1 cell cycle phase; the lower range, cells in the G2 phase; cells found in the middle of the gradient belong largely to the S phase of the cell cycle. These gradient-separated cell pools contained relatively little contamination with cells from other phases of the cell cycle and, when explanted from the gradient into fresh growth media, showed growth patterns characteristic of synchronized cell populations. This system of cell separation provides a useful tool for investigating the relationship of the cell cycle to surface membrane and metabolic characteristics in human lymphoid cell culture systems.

scholarly journals Combination Therapy of CDK4/CDK6 Inhibitor Palbociclib and Irradiation in non-Malign and Malign Cells

2020 ◽  
Author(s):  
Tina Jost ◽  
Markus Hecht ◽  
Paula Kapfer ◽  
Lucie Heinzerling ◽  
Rainer Fietkau ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Death ◽  
Cancer Cells ◽  
Cell Cycle Phase ◽  
Cycle Phase ◽  
Cell Cycle Distribution ◽  
Cell Culture Model ◽  
Culture Model ◽  
Primary Fibroblasts

Abstract Background: The CDK 4/6 kinase inhibitor palbociclib is approved for first line treatment of metastatic breast cancer in combination with hormonal therapy and investigated within clinical trials for melanoma. In metastatic disease frequently palliative radiation treatment is necessary. Due to recent findings of radiosensitizing effects of palbociclib in HNSCC and HCC, a possible influence of palbociclib on radiosensitivity was studied in malign and non-malign cells. Methods: Different tumor cells and primary fibroblasts were treated with palbociclib and ionizing radiation (IR) in 2D and 3D cell cultures. Clonogenic assays were performed to study the sensitizing effect of palbociclib on irradiation induced cytotoxicity. Apoptosis, necrosis and cell cycle distribution was analyzed by flow cytometry. Cell migration was studied with scratch assays. Results: The effect of irradiation on skin cancer cells could be slightly decreased by palbociclib in four out of eight cells comparing 2 Gy vs. 2 Gy + 1 µmol/L in the 2D cell culture model. The 3D cell culture model detected differences in cell death more sensitive than the 2D model. Necrosis was increased in primary fibroblasts (0.2 µmol/L + IR vs. IR; p = 0.0041), whereas apoptosis was decreased in skin cancer cells ICNI (0.2 µmol/L + IR vs. IR with p = 0.0005 // 2 µmol/L + IR vs. IR with p = 0.0072). Overall palbociclib attenuated radiation induced cell death in skin and breast cancer cells. In malign cells combination therapy seems to rise senescence in clonogenic assays, whereas healthy controls showed more cell death. Palbociclib did not influence cell cycle distribution in the fibroblasts but led to an accumulation of the tumor cells in G0/G1 cell cycle phase. Additionally, palbociclib decreased migration behavior of the malign and non-malign cells, but without influence on e-cadherin expression during inhibitor treatment.Conclusions: Palbociclib increases the radiosensitivity of primary fibroblasts. In cancer cells palbociclib seems to be radioprotective. This effect in cancer cells is probably based on the accumulation of cells in the less radiosensitive G0/G1 cell cycle phase. Further studies are needed to assess whether a combined therapy of palbociclib and radiation is appropriate.

ALG-2 knockdown in HeLa cells results in G2/M cell cycle phase accumulation and cell death

2009 ◽  
Vol 378 (1) ◽  
pp. 145-148 ◽  
Author(s):  
Berit R. Høj ◽  
Jonas M. la Cour ◽  
Jens Mollerup ◽  
Martin W. Berchtold
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Hela Cells ◽  
Cell Cycle Phase ◽  
Cycle Phase ◽  
M Cell ◽  
Phase Accumulation

Growth and cell cycle phase composition of fibroblasts in the reconstituted dermis model.

1990 ◽  
Vol 52 (5) ◽  
pp. 986-992
Author(s):  
Takeshi KONO ◽  
Tsukasa TANII ◽  
Masayoshi FURUKAWA ◽  
Nobuyuki MIZUNO ◽  
Shoji TANIGUCHI ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Phase Composition ◽  
Cell Cycle Phase ◽  
Cycle Phase

Reverse Screening Bioinformatics Approach to Identify Potential Anti Breast Cancer Targets Using Thymoquinone from Neutraceuticals Black Cumin Oil

2019 ◽  
Vol 19 (5) ◽  
pp. 599-609 ◽  
Author(s):  
Sumathi Sundaravadivelu ◽  
Sonia K. Raj ◽  
Banupriya S. Kumar ◽  
Poornima Arumugamand ◽  
Padma P. Ragunathan
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Cycle ◽  
Cell Death ◽  
In Silico ◽  
Chemotherapeutic Agents ◽  
Normal Cells ◽  
Black Cumin ◽  
In Silico Docking ◽  
Wide Range

Background: Functional foods, neutraceuticals and natural antioxidants have established their potential roles in the protection of human health and diseases. Thymoquinone (TQ), the main bioactive component of Nigella sativa seeds (black cumin seeds), a plant derived neutraceutical was used by ancient Egyptians because of their ability to cure a variety of health conditions and used as a dietary food supplement. Owing to its multi targeting nature, TQ interferes with a wide range of tumorigenic processes and counteracts carcinogenesis, malignant growth, invasion, migration, and angiogenesis. Additionally, TQ can specifically sensitize tumor cells towards conventional cancer treatments (e.g., radiotherapy, chemotherapy, and immunotherapy) and simultaneously minimize therapy-associated toxic effects in normal cells besides being cost effective and safe. TQ was found to play a protective role when given along with chemotherapeutic agents to normal cells. Methods: In the present study, reverse in silico docking approach was used to search for potential molecular targets for cancer therapy. Various metastatic and apoptotic targets were docked with the target ligand. TQ was also tested for its anticancer activities for its ability to cause cell death, arrest cell cycle and ability to inhibit PARP gene expression. Results: In silico docking studies showed that TQ effectively docked metastatic targets MMPs and other apoptotic and cell proliferation targets EGFR. They were able to bring about cell death mediated by apoptosis, cell cycle arrest in the late apoptotic stage and induce DNA damage too. TQ effectively down regulated PARP gene expression which can lead to enhanced cancer cell death. Conclusion: Thymoquinone a neutraceutical can be employed as a new therapeutic agent to target triple negative breast cancer which is otherwise difficult to treat as there are no receptors on them. Can be employed along with standard chemotherapeutic drugs to treat breast cancer as a combinatorial therapy.

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