Combined Treatment of γ-Tocotrienol with Statins Induce Mammary Tumor Cell Cycle Arrest in G1

2009 ◽  
Vol 234 (6) ◽  
pp. 639-650 ◽  
Author(s):  
Vikram B. Wali ◽  
Sunitha V. Bachawal ◽  
Paul W. Sylvester
Keyword(s):  
Cell Cycle ◽  
Tumor Cell ◽  
Cell Cycle Arrest ◽  
Mammary Tumor ◽  
Combined Treatment ◽  
Mammary Tumor Cell ◽  
Cycle Arrest

G1 Cell-Cycle Arrest and Apoptosis by Histone Deacetylase Inhibition in MLL-AF9 Acute Myeloid Leukemia Cells Is MLL-AF9 Independent.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4410-4410
Author(s):  
Roberto Tonelli ◽  
Roberta Sartini ◽  
Raffaele Fronza ◽  
Francesca Freccero ◽  
Monica Franzoni ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Acute Myeloid Leukemia ◽  
Cell Growth ◽  
Cell Cycle Arrest ◽  
Myeloid Leukemia ◽  
Combined Treatment ◽  
Histone Deacetylase Inhibition ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) with MLL rearrangements (MLLmut), found mainly in M5 or M4 FAB subtypes, is frequent in infants and secondary leukemias. The most common MLL translocation gives rise to MLL-AF9. MLL protein interacts with histone deacetylases (HDACs) -1 and -2 through the MLL repression domain. We report the effects of HDAC inhibition by valproic acid (VPA) in MLL-AF9 AML-M5 cells (THP-1, MM6 and MOLM-13) and MLLmut AML-M5 blasts. VPA led to histone hyper-acetylation, strong cell-growth inhibition, G1 cell-cycle arrest and apoptosis. Combined treatment with all-trans-retinoic-acid (ATRA) did not substantially improve these effects. VPA increased MLL-AF9 transcription, indicating that VPA overcomes the cell-growth promoting activity and resistance to apoptosis conferred by MLL-AF9 in AML-M5 cells, even with increased MLL-AF9. A small number of genes were significantly affected by VPA in p53-absent THP-1 cells (GeneChip analysis), and the majority of these were up-regulated. VPA potently induced p21 and cyclin G2 (CG2) expression. p21 and CG2 targeted inhibition demonstrated that p21 acts as a key regulator in the VPA-inducted G1 cell-cycle arrest, while induction of CG2 has no effect. These data suggest that these poor prognosis patients may benefit from HDAC inhibitor therapy.

scholarly journals A Fatty Acid Synthase Blockade Induces Tumor Cell-cycle Arrest by Down-regulating Skp2

2004 ◽  
Vol 279 (29) ◽  
pp. 30540-30545 ◽  
Author(s):  
Lynn M. Knowles ◽  
Fumiko Axelrod ◽  
Cecille D. Browne ◽  
Jeffrey W. Smith
Keyword(s):  
Cell Cycle ◽  
Fatty Acid ◽  
Tumor Cell ◽  
Cell Cycle Arrest ◽  
Fatty Acid Synthase ◽  
Cycle Arrest

scholarly journals Chidamide Combined With Doxorubicin Induced p53-Driven Cell Cycle Arrest and Cell Apoptosis Reverse Multidrug Resistance of Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Lixia Cao ◽  
Shaorong Zhao ◽  
Qianxi Yang ◽  
Zhendong Shi ◽  
Jingjing Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Apoptosis ◽  
Combined Treatment ◽  
Tunel Staining ◽  
Cell Cycle Distribution ◽  
Cycle Arrest

The multidrug-resistant (MDR) phenotype is usually accompanied by an abnormal expression of histone deacetylase (HDAC). Given that HDAC is vital in chromatin remodeling and epigenetics, inhibiting the role of HDAC has become an important approach for tumor treatment. However, the effect of HDAC inhibitors on MDR breast cancer has not been elucidated. This study aim to demonstrate the potential of chidamide (CHI) combined with the chemotherapy drug doxorubicin (DOX) to overcome chemotherapeutic resistance of breast cancer in vitro and in vivo, laying the experimental foundation for the next clinical application. The results showed that, CHI combined with DOX showed significant cytotoxicity to MDR breast cancer cells in vitro and in vivo compared with the CHI monotherapy. The cell cycle distribution results showed that CHI caused G0/G1 cell cycle arrest and inhibited cell growth regardless of the addition of DOX. At the same time, annexin V staining and TUNEL staining results showed that CHI enhanced the number of cell apoptosis in drug-resistant cells. The western blot analysis found that p53 was activated in the CHI-treated group and combined treatment group, and then the activated p53 up-regulated p21, apoptosis regulator recombinant protein (Puma), and pro-apoptotic protein Bax, down-regulated the apoptotic proteins Bcl-xL and Bcl-2, and activated the caspase cascade to induce apoptosis.

scholarly journals In Vitro Anticancer Effects of All-trans Retinoic Acid in Combination with Dacarbazine against CD117+ Melanoma Cells

Drug Research ◽  
2020 ◽  
Vol 70 (12) ◽  
pp. 563-569
Author(s):  
Bahareh Mohammadi Jobani ◽  
Elham Mohebi ◽  
Nowruz Najafzadeh
Keyword(s):  
Cell Cycle ◽  
Retinoic Acid ◽  
Malignant Melanoma ◽  
Cell Cycle Arrest ◽  
Combined Treatment ◽  
Melanoma Cells ◽  
Cycle Arrest ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract Background Malignant melanoma is a common form of skin cancer that contains different cell types recognized by various cell surface markers. Dacarbazine-based combination chemotherapy is frequently used for the treatment of melanoma. Despite its potent anticancer properties, resistance to dacarbazine develops in malignant melanoma. Here, we aim to improve response to dacarbazine therapy by pretreatment with all-trans retinoic acid (ATRA) in CD117+ melanoma cells. Methods The CD117+ melanoma cells were sorted from A375 malignant melanoma cell line using magnetic-activated cell sorting (MACS). The cell viability was examined by cell proliferation assay (MTT). Apoptosis was determined by acridine orange/ ethidium bromide staining. Indeed, we performed flow cytometry to evaluate the cell cycle arrest. Results Here, the CD117+ melanoma cells were incubated with various concentrations of ATRA, dacarbazine, and their combination to determine IC50 values. We found that 20 µM ATRA treatment followed by dacarbazine was found to be more effective than dacarbazine alone. There was an indication that the combination of ATRA with dacarbazine (ATRA/dacarbazine) caused more apoptosis and necrosis in the melanoma cells (P<0.05). Furthermore, ATRA/dacarbazine treatment inhibited the cell at the G0/G1 phase, while dacarbazine alone inhibited the cells at S phase. Conclusion Collectively, combined treatment with ATRA and dacarbazine induced more apoptosis and enhanced the cell cycle arrest of CD117+ melanoma cells. These results suggested that ATRA increased the sensitivity of melanoma cells to the effect of dacarbazine.

scholarly journals Sorafenib in Combination with Betulinic Acid Synergistically Induces Cell Cycle Arrest and Inhibits Clonogenic Activity in Pancreatic Ductal Adenocarcinoma Cells

2018 ◽  
Vol 19 (10) ◽  
pp. 3234 ◽  
Author(s):  
Justyna Kutkowska ◽  
Leon Strzadala ◽  
Andrzej Rapak
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Betulinic Acid ◽  
Combined Treatment ◽  
Ductal Adenocarcinoma ◽  
Pdac Cell ◽  
Cycle Arrest

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly cancers in the world due to late diagnosis and poor response to available treatments. It is important to identify treatment strategies that will increase the efficacy and reduce the toxicity of the currently used therapeutics. In this study, the PDAC cell lines AsPC-1, BxPC-3, and Capan-1 were treated with sorafenib and betulinic acid alone and in combination. We examined the effect of combined treatments on viability (MTS test), proliferation and apoptosis (annexin V staining), cell cycle arrest (PI staining), alterations in signaling pathways (Western blotting), and colony-forming ability. The combination of sorafenib with betulinic acid inhibited the viability and proliferation of PDAC cells without the induction of apoptosis. The antiproliferative effect, caused by G2 cell cycle arrest, was strongly associated with increased expression of p21 and decreased expression of c-Myc and cyclin D1, and was induced only by combined treatment. Additionally, decreased proliferation could also be associated with the inhibition of the P13K/Akt and MAPK signaling pathways. Importantly, combination treatment reduced the colony-forming ability of PDAC cells, as compared to both compounds alone. Collectively, we showed that combined treatment with low concentrations of sorafenib and betulinic acid had the capacity to inhibit proliferation and abolish clonogenic activity in PDAC cell lines.

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