Short-Term Exposure of Cancer Cells to Micromolar Doses of Paclitaxel, with or without Hyperthermia, Induces Long-Term Inhibition of Cell Proliferation and Cell Death In Vitro

2007 ◽  
Vol 14 (3) ◽  
pp. 1220-1228 ◽  
Author(s):  
John Michalakis ◽  
Spyros D. Georgatos ◽  
Eelco de Bree ◽  
Hara Polioudaki ◽  
John Romanos ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Cancer Cells ◽  
Short Term ◽  
Short Term Exposure

scholarly journals Transient Receptor Potential Cation Channels in Cancer Therapy

2019 ◽  
Vol 7 (12) ◽  
pp. 108 ◽  
Author(s):  
Giorgio Santoni ◽  
Federica Maggi ◽  
Maria Beatrice Morelli ◽  
Matteo Santoni ◽  
Oliviero Marinelli
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Cancer Cells ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Chemotherapeutic Agents ◽  
Migration And Invasion ◽  
Transient Receptor

In mammals, the transient receptor potential (TRP) channels family consists of six different families, namely TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPML (mucolipin), TRPP (polycystin), and TRPA (ankyrin), that are strictly connected with cancer cell proliferation, differentiation, cell death, angiogenesis, migration, and invasion. Changes in TRP channels’ expression and function have been found to regulate cell proliferation and resistance or sensitivity of cancer cells to apoptotic-induced cell death, resulting in cancer-promoting effects or resistance to chemotherapy treatments. This review summarizes the data reported so far on the effect of targeting TRP channels in different types of cancer by using multiple TRP-specific agonists, antagonists alone, or in combination with classic chemotherapeutic agents, microRNA specifically targeting the TRP channels, and so forth, and the in vitro and in vivo feasibility evaluated in experimental models and in cancer patients. Considerable efforts have been made to fight cancer cells, and therapies targeting TRP channels seem to be the most promising strategy. However, more in-depth investigations are required to completely understand the role of TRP channels in cancer in order to design new, more specific, and valuable pharmacological tools.

Therapeutic Targeting of the Bcl2 Family

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. SCI-42-SCI-42
Author(s):  
Anthony Letai ◽  
Matthew S. Davids ◽  
Triona Ni Chonghaile ◽  
Jing Deng ◽  
Luv Patel
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Lymphoblastic Leukemia ◽  
Lymphocytic Leukemia ◽  
Mitochondrial Outer Membrane ◽  
Short Term ◽  
Provocative Test ◽  
Mitochondrial Outer Membrane Permeabilization

Abstract Many, perhaps most, cancer chemotherapy agents kill cancer cells via the mitochondrial pathway of apoptosis that is controlled by the Bcl-2 family of proteins. Bcl-2 family proteins regulate commitment to cell death by controlling mitochondrial outer membrane permeabilization (MOMP). To better understand how cancer cells commit to apoptosis, and what drugs might make them commit to apoptosis, we have studied perturbing mitochondria with BH3 peptides that are derived from pro-death Bcl-2 family proteins. Using this provocative test, which we call BH3 profiling, we are able to measure how close a cell is to the threshold of apoptosis, a property we call “priming”. Priming corresponds to sensitivity to chemotherapy. Moreover, BH3 profiling can be used to detect dependence on Bcl-2 and Bcl-xL for survival, which predicts cytotoxic response to small molecule antagonists such as ABT-199 and ABT-263. In acute lymphoblastic leukemia, we find that dependence on either Bcl-2 or Bcl-xL varies from case to case, with very important consequences for sensitivity to ABT-199 and ABT-263. In chronic lymphocytic leukemia, ABT-199 has already demonstrated significant clinical activity that corresponds to its on-target activity in mitochondria in vitro. We have been testing how this in vitro mitochondrial activity in BH3 profiling assays might be translated into a useful clinical predictive biomarker. Finally, we can measure how short term incubation with many kinds of drugs, including targeted pathway inhibitors, can increase cancer cell priming, including for primary lymphoid malignancy cells. This short term increase in priming predicts subsequent cancer cell death, including in clinical treatment. We call this method “Dynamic BH3 Profiling” and are exploring how it might best be utilized in the clinic. Disclosures: Letai: Dana-Farber Cancer Institute: Patents & Royalties; AbbVie: Consultancy.

Direct upregulation of parathyroid calcium-sensing receptor and vitamin D receptor by calcimimetics in uremic rats

2009 ◽  
Vol 296 (3) ◽  
pp. F605-F613 ◽  
Author(s):  
Francisco J. Mendoza ◽  
Ignacio Lopez ◽  
Rocio Canalejo ◽  
Yolanda Almaden ◽  
David Martin ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Term Treatment ◽  
Parathyroid Cell ◽  
Calcium Sensing Receptor ◽  
Short Term ◽  
Calcium Sensing ◽  
Long Term Treatment ◽  
Acute Increase

To investigate whether the effect of the calcimimetic AMG 641 and calcitriol on CaSR and VDR expression could be separated from their ability to reduce parathyroid cell proliferation, five-sixth nephrectomized (5/6 Nx) rats received vehicle, AMG 641, calcitriol, or AMG 641+calcitriol either daily for 13 days (long-term protocol) or in a single dose (short-term protocol). In the long-term protocol, AMG 641, calcitriol, and their combination significantly reduced the percentage of proliferating parathyroid cells. Proliferation was uncontrolled in the short-term protocol. A significant increase in CaSR mRNA (% vs. β-actin) was detected in rats treated with both calcitriol (1.60 ± 0.30) and AMG 641 (1.66 ± 0.25) for 13 days ( P = 0.01 vs. 5/6 Nx+vehicle, 0.89 ± 0.09); and there was a further increase when both drugs were administered simultaneously (2.46 ± 0.33). In the short-term protocol, only rats receiving AMG 641 alone (2.01 ± 0.33, P < 0.001) showed increased expression of CaSR mRNA, whereas the combination (1.81 ± 0.20) produced no additional benefit. AMG 641 also increased CaSR mRNA expression in vitro. Changes in VDR mRNA paralleled those of CaSR mRNA. In the long-term treatment, both AMG 641 (0.87 ± 0.14) and calcitriol (0.99 ± 0.12) increased VDR mRNA ( P < 0.05 vs. 5/6 Nx+vehicle, 0.49 ± 0.10), and the increase was more accentuated when the drugs were combined (1.49 ± 0.45). In the short-term protocol, only treatment with AMG 641, alone (1.52 ± 0.41) or combined with calcitriol (1.86 ± 0.24), increased VDR mRNA. In conclusion, our results demonstrate an acute increase in CaSR mRNA and VDR mRNA in the parathyroid glands of uremic rats treated with AMG 641, in which cell proliferation was uncontrolled, thus supporting a direct effect of calcimimetics on CaSR and VDR expression by hyperplastic parathyroid cells.

scholarly journals A Potential Antineoplastic Peptide of Human Prostate Cancer Cells Derived from the Lesser Spotted Dogfish (Scyliorhinus canicula L.)

Marine Drugs ◽  
2019 ◽  
Vol 17 (10) ◽  
pp. 585 ◽  
Author(s):  
Adrien Bosseboeuf ◽  
Amandine Baron ◽  
Elise Duval ◽  
Aude Gautier ◽  
Pascal Sourdaine ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cell Death ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Prostate Cancer Cells ◽  
Cell Death Mechanisms ◽  
Autophagy Inhibition

The purpose of the present paper is to investigate the mechanism of action of a pyroglutamate-modified peptide (pE-K092D) on in vitro growth inhibition of MDA-Pca-2b prostate cancer cells. This peptide was derived from a peptide previously isolated from the testis of the lesser spotted dogfish and identified as QLTPEALADEEEMNALAAR (K092D). The effect of the peptide on cell proliferation and cell death mechanisms was studied by flow cytometry. Cellular morphology and cytoskeleton integrity of peptide-treated cells were observed by immunofluorescence microscopy. Results showed the onset of peptide induced early cytoskeleton perturbation, inhibition of autophagy, inhibition of cell proliferation and, at the end, non-apoptotic cell death mechanisms (membrane destabilization and necrosis). All those mechanisms seem to contribute to MDA-Pca-2b growth inhibition by a main cytostatic fate.

scholarly journals Fructose-a double edged sword for cell death versus differentiation and long-term survival of NSC-34 motor neuron like cells in vitro

2021 ◽  
Author(s):  
Divya Lodha ◽  
Jamuna R. Subramaniam
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Motor Neurons ◽  
Response Regulator ◽  
Nuclear Staining ◽  
Term Survival ◽  
High Fructose

Abstract In various neurological and neurodegenerative diseases (ND), motor neurons (MN) of the spinal cord are affected leading to movement impairments. The ND, Amyotrophic Lateral Sclerosis (ALS), is caused due to MN degeneration. ALS afflicts athletes and other major sports personalities, who generally consume fructose enriched sports drinks. Recently, we have reported that high fructose (F5%) impairs the metabolic activity in the NSC-34, MN cell line and reduces the healthspan of C. elegans. But how fructose impacts the MNs either in vitro or in vivo in the long term is not understood. Here we report, to our surprise, that high fructose (F5%) treatment of NSC-34 leads to differentiation of 1-2% of cells with progressive neurite extension. They could be maintained for 80 days in vitro with 5% CO2 and O2 at 18.8%. On the contrary, 5% fructose significantly reduced cell viability by ~85% and inhibited cell proliferation by Day10. Nuclear staining displayed multiple nuclei in the cells indicative of cytokinesis inhibition which led to the lack of cell proliferation. Further, F5% significantly increased ROS levels (^~34%), the potential cause for reduced viability. In addition, no induction of expression of the master oxidative stress response regulator, the transcription factor, nrf-2, or the downstream effector, sod1, was evident. Despite the adverse effects, in the absence of any, F5% is a potential strategy to maintain at least a small percentage of MNs for a long time, ~45 days in vitro, which also reinforces the Redox-Cell death versus cell survival conundrum.

ATL

2014 ◽  
Vol 24 (3) ◽  
pp. 437-443 ◽  
Author(s):  
Jie Li ◽  
Geng Cui ◽  
Lu Sun ◽  
Shu-Juan Wang ◽  
Shuang Tian ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cell Death ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Apoptosis ◽  
Cancer Cell Death ◽  
Ovarian Cells

ObjectiveARHIis a maternally imprinted tumor suppressor gene that is responsible for initiating programmed cell death and inhibiting cancer cell growth. However, the influence ofARHIon epithelial ovarian cancer cell death and the underlying mechanisms behind howARHIregulates cancer cells still require further studies.MethodsEpithelial ovarian cancer cells TOV112D and ES-2 were used in this in vitro study. Cell proliferation, apoptosis, and autophagy activities were compared in TOV112D and ES-2 cells transfected withARHIvectors or control vectors. Bcl-2 siRNA was transfected into TOV112D cells to investigate the roles of Bcl-2 played in regulating apoptosis and autophagy.ResultsARHIexpression was reduced in TOV112D and ES-2 cells compared with normal epithelial ovarian cells (NOE095 and HOSEpiC). OverexpressedARHIinhibited cancer cell proliferation, whereas induced forced cell apoptosis and excessive formation of autophagosomes inhibited promoted cell death. Furthermore, we found that Bcl-2 expression moderately declined in response toARHIoverexpressing in ES-2 and TOV112D cells; meanwhile, more apoptotic cells and higher LC3 level presented after silence of Bcl-2 in TOV112D cells. Reduced Bcl-2–Beclin 1 complex were observed inARHIoverexpressing cells. Moreover, modulation ofARHIto Bcl-2 expression could be ascribed partially to the activation of PI3k/AKT pathway. The addition of LY294002 enabled to suppress Bcl-2 expression and cell proliferation.ConclusionsThe silence ofARHIexpression in vitro seems to accelerate the malignant transformation of healthy ovarian cells by restraining apoptosis and autophagy. The overexpressedARHIin TOV112D cancer cells suppresses the activation of PI3K/AKT and reduces the expression of Bcl-2, leading to enhanced cell apoptosis and autophagic cancer cell death.

scholarly journals Macrophages of diverse phenotypes drive vascularization of engineered tissues

2020 ◽  
Vol 6 (18) ◽  
pp. eaay6391 ◽  
Author(s):  
P. L. Graney ◽  
S. Ben-Shaul ◽  
S. Landau ◽  
A. Bajpai ◽  
B. Singh ◽  
...  
Keyword(s):  
Blood Vessel ◽  
Cell Behavior ◽  
Short Term ◽  
M1 Macrophages ◽  
Sprouting Angiogenesis ◽  
Engineered Tissues ◽  
Short Term Exposure ◽  
Vessel Networks

Macrophages are key contributors to vascularization, but the mechanisms behind their actions are not understood. Here, we show that diverse macrophage phenotypes have distinct effects on endothelial cell behavior, with resulting effects on vascularization of engineered tissues. In Transwell coculture, proinflammatory M1 macrophages caused endothelial cells to up-regulate genes associated with sprouting angiogenesis, whereas prohealing (M2a), proremodeling (M2c), and anti-inflammatory (M2f) macrophages promoted up-regulation of genes associated with pericyte cell differentiation. In 3D tissue-engineered human blood vessel networks in vitro, short-term exposure (1 day) to M1 macrophages increased vessel formation, while long-term exposure (3 days) caused regression. When human tissue-engineered blood vessel networks were implanted into athymic mice, macrophages expressing markers of both M1 and M2 phenotypes wrapped around and bridged adjacent vessels and formed vessel-like structures themselves. Last, depletion of host macrophages inhibited remodeling of engineered vessels, infiltration of host vessels, and anastomosis with host vessels.

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