scholarly journals The Synergistic Effect of Doxorubicin and Ethanolic Extracts of Caesalpinia sappan L. Wood and Ficus septica Burm. f. Leaves on Viability, Cell Cycle Progression, and Apoptosis Induction of MCF­7 Cells

2017 ◽  
Vol 21 (1) ◽  
pp. 29 ◽  
Author(s):  
Sari Haryanti ◽  
Suwijiyo Pramono ◽  
Retno Murwanti ◽  
Edy Meiyanto

Caesalpinia sappan L. and Ficus septica Burm. f  known asa potential plant with wide variety of medicinal properties, including anticancer. Present study was aimed to explore cytotoxic effect ofsappan wood (ECS) and awar-awar leaves (EFS), and its combination with doxorubicin (dox) on MCF-7 cells focusing on cell cycle progression and apoptosis induction.The result of MTT assay showed that single treatment of ECS and dox performed cytotoxic effect with the IC50 value of 32 µg/mL and 6 µM respectively, while EFS performed low cytotoxic effect with the IC50 value of 282 µg/mL. The combination of ECS with EFS and doxorubicin showed synergistic cytotoxic effect. Flow cytometry analysis revealed that combination of ECS (16 µg/mL) with EFS (8 µg/mL) and doxorubicin (2 µM) induced apoptosis, and cell accumulation at sub-G1 and G2/M phases.Immunoblotting assay confirmed the apoptosis induction of this combination through increasing of cleavage of PARP-1. Based on these results, the synergistic cytotoxic effect of this combinationwas through G2/M phase accumulation and apoptosis inductionand potentially to be developed as co-chemotherapeutic agent.

2018 ◽  
Vol 23 (1) ◽  
pp. 7 ◽  
Author(s):  
Sari Haryanti ◽  
Yuli Widiyastuti ◽  
Slamet Wahyono

Gerrardanthus macrorhizus (GM) caudex, is traditionally used in cancer therapy by the Tetun people in Belu District, East Nusa Tenggara Province, Indonesia, where it is known as “akar batu”. This study aimed to explore the cytotoxic effects of G. macrorhizus caudex aqueous extract, as well as its combination with doxorubicin, on MCF-7 cells. Also investigated were the possible mechanisms of interaction through cell cycle progression and apoptosis induction. Single treatments of 5–320 µg/mL of the extract showed morphological alterations in MCF-7 cells, but did not show any cytotoxic effect. Combining the extract with doxorubicin resulted in a synergistic cytotoxic effect. Doxorubicin concentrations equivalent to 1/12, 1/8, and 1/5 fold of the IC50 combined with 20 µg/mL decreased viability to 48%. We then explored the combination effect of doxorubicin 0.4 µM with GM 5 and 20 µg/mL using a flow cytometer. A low concentration of the extract (5 µg/mL) combined with 0.4 µM of doxorubicin resulted in slight cell cycle modulation by G1, G2M arrested and apoptosis induction. The combination of doxorubicin and a higher concentration of the extract (20 µg/mL) did not show cell cycle modulation, and led to necrosis. Therefore, G. macrorhizus caudex at low concentrations has the potential to be developed further as a co-chemotherapeutic agent.


2012 ◽  
Vol 80 (4) ◽  
pp. 1467-1478 ◽  
Author(s):  
Carolina Coelho ◽  
Lydia Tesfa ◽  
Jinghang Zhang ◽  
Johanna Rivera ◽  
Teresa Gonçalves ◽  
...  

ABSTRACTWe investigated the outcome of the interaction ofCryptococcus neoformanswith murine macrophages using laser scanning cytometry (LSC). Previous results in our lab had shown that phagocytosis ofC. neoformanspromoted cell cycle progression. LSC allowed us to simultaneously measure the phagocytic index, macrophage DNA content, and 5-ethynyl-2′-deoxyuridine (EdU) incorporation such that it was possible to study host cell division as a function of phagocytosis. LSC proved to be a robust, reliable, and high-throughput method for quantifying phagocytosis. Phagocytosis ofC. neoformanspromoted cell cycle progression, but infected macrophages were significantly less likely to complete mitosis. Hence, we report a new cytotoxic effect associated with intracellularC. neoformansresidence that manifested itself in impaired cell cycle completion as a consequence of a block in the G2/M stage of the mitotic cell cycle. Cell cycle arrest was not due to increased cell membrane permeability or DNA damage. We investigated alveolar macrophage replicationin vivoand demonstrated that these cells are capable of low levels of cell division in the presence or absence ofC. neoformansinfection. In summary, we simultaneously studied phagocytosis, the cell cycle state of the host cell and pathogen-mediated cytotoxicity, and our results demonstrate a new cytotoxic effect ofC. neoformansinfection on murine macrophages: fungus-induced cell cycle arrest. Finally, we provide evidence for alveolar macrophage proliferationin vivo.


PLoS ONE ◽  
2014 ◽  
Vol 9 (12) ◽  
pp. e116048 ◽  
Author(s):  
Hitomi Hasegawa ◽  
Kenichi Ishibashi ◽  
Shoichi Kubota ◽  
Chihiro Yamaguchi ◽  
Ryuzaburo Yuki ◽  
...  

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3327
Author(s):  
Zhixiang Wang

The cell cycle is the series of events that take place in a cell, which drives it to divide and produce two new daughter cells. The typical cell cycle in eukaryotes is composed of the following phases: G1, S, G2, and M phase. Cell cycle progression is mediated by cyclin-dependent kinases (Cdks) and their regulatory cyclin subunits. However, the driving force of cell cycle progression is growth factor-initiated signaling pathways that control the activity of various Cdk–cyclin complexes. While the mechanism underlying the role of growth factor signaling in G1 phase of cell cycle progression has been largely revealed due to early extensive research, little is known regarding the function and mechanism of growth factor signaling in regulating other phases of the cell cycle, including S, G2, and M phase. In this review, we briefly discuss the process of cell cycle progression through various phases, and we focus on the role of signaling pathways activated by growth factors and their receptor (mostly receptor tyrosine kinases) in regulating cell cycle progression through various phases.


2005 ◽  
Vol 25 (13) ◽  
pp. 5725-5737 ◽  
Author(s):  
Kazuhiro Katayama ◽  
Naoya Fujita ◽  
Takashi Tsuruo

ABSTRACT The serine/threonine kinase Akt is known to promote cell growth by regulating the cell cycle in G1 phase through activation of cyclin/Cdk kinases and inactivation of Cdk inhibitors. However, how the G2/M phase is regulated by Akt remains unclear. Here, we show that Akt counteracts the function of WEE1Hu. Inactivation of Akt by chemotherapeutic drugs or the phosphatidylinositide-3-OH kinase inhibitor LY294002 induced G2/M arrest together with the inhibitory phosphorylation of Cdc2. Because the increased Cdc2 phosphorylation was completely suppressed by wee1hu gene silencing, WEE1Hu was associated with G2/M arrest induced by Akt inactivation. Further analyses revealed that Akt directly bound to and phosphorylated WEE1Hu during the S to G2 phase. Serine-642 was identified as an Akt-dependent phosphorylation site. WEE1Hu kinase activity was not affected by serine-642 phosphorylation. We revealed that serine-642 phosphorylation promoted cytoplasmic localization of WEE1Hu. The nuclear-to-cytoplasmic translocation was mediated by phosphorylation-dependent WEE1Hu binding to 14-3-3θ but not 14-3-3β or -σ. These results indicate that Akt promotes G2/M cell cycle progression by inducing phosphorylation-dependent 14-3-3θ binding and cytoplasmic localization of WEE1Hu.


2020 ◽  
Vol 21 (23) ◽  
pp. 9166
Author(s):  
Shigeru Hanamata ◽  
Takamitsu Kurusu ◽  
Kazuyuki Kuchitsu

Autophagy is ubiquitous in eukaryotic cells and plays an essential role in stress adaptation and development by recycling nutrients and maintaining cellular homeostasis. However, the dynamics and regulatory mechanisms of autophagosome formation during the cell cycle in plant cells remain poorly elucidated. We here analyzed the number of autophagosomes during cell cycle progression in synchronized tobacco BY-2 cells expressing YFP-NtATG8a as a marker for the autophagosomes. Autophagosomes were abundant in the G2 and G1 phases of interphase, though they were much less abundant in the M and S phases. Autophagosomes drastically decreased during the G2/M transition, and the CDK inhibitor roscovitine inhibited the G2/M transition and the decrease in autophagosomes. Autophagosomes were rapidly increased by a proteasome inhibitor, MG-132. MG-132-induced autophagosome formation was also markedly lower in the M phases than during interphase. These results indicate that the activity of autophagosome formation is differently regulated at each cell cycle stage, which is strongly suppressed during mitosis.


1992 ◽  
Vol 263 (5) ◽  
pp. H1331-H1338 ◽  
Author(s):  
T. Nagata ◽  
Y. Uehara ◽  
A. Numabe ◽  
T. Ishimitsu ◽  
N. Hirawa ◽  
...  

We investigated the regulatory effects of the vasoconstrictor thromboxane A2 on the proliferation of vascular smooth muscle cells (VSMC) from Wistar-Kyoto rats using 9,11-epithio-11,12-methano-thromboxane A2 (STA2), a stable analogue of thromboxane A2. STA2 dose dependently increased incorporation of [3H]thymidine into DNA in randomly cycling VSMC and significantly shortened the doubling time. Cell cycle analysis revealed that the increased cell cycle progression was primarily due to a rapid transition from the DNA synthetic (S) to the G2/mitotic (M) phase. Moreover, STA2 enhanced protein synthesis in VSMC during the G2/M phase, whereas the protein synthesis was unaffected in the G0/G1 period. In fact, STA2 prompted the cells in G2/M phase to synthesize actin, a major cytoskeleton protein. Conversely, inhibition of protein synthesis by puromycin retarded the transition from S to G2/M. In addition, depolymerization of the actin molecules by cytochalasin D offset the quick progression to the G2/M phase by STA2. These data indicate that thromboxane A2 stimulates the cell cycle progression in VSMC primarily through a rapid transition from S to G2/M. This enhanced progression is attributable partly to a rapid buildup of the cytoskeleton proteins during the G2/M period.


1999 ◽  
Vol 257 (2) ◽  
pp. 460-465 ◽  
Author(s):  
Maria Giuseppina Monti ◽  
Stefania Ghiaroni ◽  
Daniela Barbieri ◽  
Claudio Franceschi ◽  
Gaetano Marverti ◽  
...  

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