Induction of Apoptosis and Cell Cycle Blockade by Helichrysetin in A549 Human Lung Adenocarcinoma Cells

Researchers are looking into the potential development of natural compounds for anticancer therapy. Previous studies have postulated the cytotoxic effect of helichrysetin towards different cancer cell lines. In this study, we investigated the cytotoxic effect of helichrysetin, a naturally occurring chalcone on four selected cancer cell lines, A549, MCF-7, Ca Ski, and HT-29, and further elucidated its biochemical and molecular mechanisms in human lung adenocarcinoma, A549. Helichrysetin showed the highest cytotoxic activity against Ca Ski followed by A549. Changes in the nuclear morphology of A549 cells such as chromatin condensation and nuclear fragmentation were observed in cells treated with helichrysetin. Further evidence of apoptosis includes the externalization of phosphatidylserine and the collapse of mitochondrial membrane potential which are both early signs of apoptosis. These signs of apoptosis are related to cell cycle blockade at the S checkpoint which suggests that the alteration of the cell cycle contributes to the induction of apoptosis in A549. These results suggest that helichrysetin has great potentials for development as an anticancer agent.

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Molecular Mechanisms Underlying Yatein-Induced Cell-Cycle Arrest and Microtubule Destabilization in Human Lung Adenocarcinoma Cells

Cancers ◽

10.3390/cancers11091384 ◽

2019 ◽

Vol 11 (9) ◽

pp. 1384 ◽

Cited By ~ 3

Author(s):

Shang-Tse Ho ◽

Chi-Chen Lin ◽

Yu-Tang Tung ◽

Jyh-Horng Wu

Keyword(s):

Cell Cycle ◽

Antitumor Activity ◽

Lung Adenocarcinoma ◽

Cell Cycle Progression ◽

Molecular Mechanisms ◽

Human Lung ◽

Microtubule Dynamics ◽

Cycle Progression ◽

Human Lung Adenocarcinoma

Yatein is an antitumor agent isolated from Calocedrus formosana Florin leaves extract. In our previous study, we found that yatein inhibited the growth of human lung adenocarcinoma A549 and CL1-5 cells by inducing intrinsic and extrinsic apoptotic pathways. To further uncover the effects and mechanisms of yatein-induced inhibition on A549 and CL1-5 cell growth, we evaluated yatein-mediated antitumor activity in vivo and the regulatory effects of yatein on cell-cycle progression and microtubule dynamics. Flow cytometry and western blotting revealed that yatein induces G2/M arrest in A549 and CL1-5 cells. Yatein also destabilized microtubules and interfered with microtubule dynamics in the two cell lines. Furthermore, we evaluated the antitumor activity of yatein in vivo using a xenograft mouse model and found that yatein treatment altered cyclin B/Cdc2 complex expression and significantly inhibited tumor growth. Taken together, our results suggested that yatein effectively inhibited the growth of A549 and CL1-5 cells possibly by disrupting cell-cycle progression and microtubule dynamics.

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Sulforaphane Reduces Prostate Cancer Cell Growth and Proliferation In Vitro by Modulating the Cdk-Cyclin Axis and Expression of the CD44 Variants 4, 5, and 7

International Journal of Molecular Sciences ◽

10.3390/ijms21228724 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8724

Author(s):

Jochen Rutz ◽

Sarah Thaler ◽

Sebastian Maxeiner ◽

Felix K.-H. Chun ◽

Roman A. Blaheta

Keyword(s):

Prostate Cancer ◽

Cell Cycle ◽

Cell Growth ◽

Cell Lines ◽

Cancer Cell ◽

Intracellular Signaling ◽

Molecular Mechanisms ◽

Prostate Cancer Cell ◽

Cancer Cell Lines ◽

Prostate Cancer Cell Lines

Prostate cancer patients whose tumors develop resistance to conventional treatment often turn to natural, plant-derived products, one of which is sulforaphane (SFN). This study was designed to determine whether anti-tumor properties of SFN, identified in other tumor entities, are also evident in cultivated DU145 and PC3 prostate cancer cells. The cells were incubated with SFN (1–20 µM) and tumor cell growth and proliferative activity were evaluated. Having found a considerable anti-growth, anti-proliferative, and anti-clonogenic influence of SFN on both prostate cancer cell lines, further investigation into possible mechanisms of action were performed by evaluating the cell cycle phases and cell-cycle-regulating proteins. SFN induced a cell cycle arrest at the S- and G2/M-phase in both DU145 and PC3 cells. Elevation of histone H3 and H4 acetylation was also evident in both cell lines following SFN exposure. However, alterations occurring in the Cdk-cyclin axis, modification of the p19 and p27 proteins and changes in CD44v4, v5, and v7 expression because of SFN exposure differed in the two cell lines. SFN, therefore, does exert anti-tumor properties on these two prostate cancer cell lines by histone acetylation and altering the intracellular signaling cascade, but not through the same molecular mechanisms.

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Increased radiosensitivity of HPV-positive head and neck cancer cell lines due to cell cycle dysregulation and induction of apoptosis

Strahlentherapie und Onkologie ◽

10.1007/s00066-014-0605-5 ◽

2014 ◽

Vol 190 (9) ◽

pp. 839-846 ◽

Cited By ~ 58

Author(s):

Andrea Arenz ◽

Frank Ziemann ◽

Christina Mayer ◽

Andrea Wittig ◽

Kirstin Dreffke ◽

...

Keyword(s):

Cell Cycle ◽

Head And Neck Cancer ◽

Head And Neck ◽

Cell Lines ◽

Cancer Cell ◽

Neck Cancer ◽

Cancer Cell Lines ◽

Induction Of Apoptosis

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A Phenylacetamide Resveratrol Derivative Exerts Inhibitory Effects on Breast Cancer Cell Growth

International Journal of Molecular Sciences ◽

10.3390/ijms22105255 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5255

Author(s):

Adele Chimento ◽

Anna Santarsiero ◽

Domenico Iacopetta ◽

Jessica Ceramella ◽

Arianna De Luca ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Estrogen Receptor ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Molecular Mechanisms ◽

Cancer Cell Lines ◽

Breast Cancer Cell Lines ◽

Antiproliferative Effects

Resveratrol (RSV) is a natural compound that displays several pharmacological properties, including anti-cancer actions. However, its clinical application is limited because of its low solubility and bioavailability. Here, the antiproliferative and anti-inflammatory activity of a series of phenylacetamide RSV derivatives has been evaluated in several cancer cell lines. These derivatives contain a monosubstituted aromatic ring that could mimic the RSV phenolic nucleus and a longer flexible chain that could confer a better stability and bioavailability than RSV. Using MTT assay, we demonstrated that most derivatives exerted antiproliferative effects in almost all of the cancer cell lines tested. Among them, derivative 2, that showed greater bioavailability than RSV, was the most active, particularly against estrogen receptor positive (ER+) MCF7 and estrogen receptor negative (ER-) MDA-MB231 breast cancer cell lines. Moreover, we demonstrated that these derivatives, particularly derivative 2, were able to inhibit NO and ROS synthesis and PGE2 secretion in lipopolysaccharide (LPS)-activated U937 human monocytic cells (derived from a histiocytoma). In order to define the molecular mechanisms underlying the antiproliferative effects of derivative 2, we found that it determined cell cycle arrest at the G1 phase, modified the expression of cell cycle regulatory proteins, and ultimately triggered apoptotic cell death in both breast cancer cell lines. Taken together, these results highlight the studied RSV derivatives, particularly derivative 2, as promising tools for the development of new and more bioavailable derivatives useful in the treatment of breast cancer.

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Evaluation of Terpenes Psiadin, Plectranthone, and Saudinolide as Selective Anti-Cancer Agents against Hepatic Carcinoma Cells

10.20944/preprints202012.0591.v1 ◽

2020 ◽

Author(s):

Khaled Y. Orabi ◽

Mohamed S. Abaza ◽

Rajaa Al-Attiyah ◽

Yunus A. Luqmani

Keyword(s):

Cell Cycle ◽

Cell Lines ◽

Cancer Cell ◽

Cell Cycle Progression ◽

Molecular Mechanisms ◽

Therapeutic Potential ◽

Cancer Cell Lines ◽

Chemotherapeutic Agents ◽

Isolation And Purification

: Plant-derived terpenes have aroused considerable interest as chemotherapeutic agents for a variety of diseases. This study aimed at the isolation and purification of the scarce terpenes psiadin, plectranthone and saudinolide from their respective plants, followed by the determination of antiproliferative activity, against hepatic cancer cell lines (HepG2, Hep3B), and the potential molecular mechanisms. Time- and dose-dependent cytotoxicity, evaluated using MTT and colony-forming assays, were exhibited by psiadin and plectranthone against the cancer cells. Flow cytometry showed that these two terpenes blocked cell cycle progression and induced mitochondrial-mediated apoptosis, particularly through increased cytochrome c and disruption of mitochondrial membrane potential. Additionally, they initiated the generation of reactive oxygen species as well as inhibiting NF-B. Psiadin lowered several essential cyclins and cyclin-dependent kinases and reduced RB activation. It was concluded that psiadin, in particular, has a significant therapeutic potential with the biggest advantage of differentiating between cancer and normal cells which is acutely lacking in current cytotoxic drugs. Its precise mode of action needs further investigation but appears predominantly to cause cell cycle arrest by interfering with cyclin production. It will be important to determine, in future studies, whether these terpenes will similarly inhibit other cancer cell lines and retain its activity against tumors in vivo.

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Polyadenylate polymerase modulations in human epithelioid cervix and breast cancer cell lines, treated with etoposide or cordycepin, follow cell cycle rather than apoptosis induction

Biological Chemistry ◽

10.1515/bc.2005.056 ◽

2005 ◽

Vol 386 (5) ◽

pp. 471-480 ◽

Cited By ~ 30

Author(s):

Hellinida Thomadaki ◽

Chris M. Tsiapalis ◽

Andreas Scorilas

Keyword(s):

Cell Cycle ◽

Cell Lines ◽

Cancer Cell ◽

Cell Cycle Progression ◽

Cancer Cell Lines ◽

Apoptosis Induction ◽

Activity Assay ◽

Epithelial Cancer ◽

Cycle Progression ◽

Induction Of Apoptosis

AbstractCancer results from an imbalance between cell cycle progression and apoptosis. Therefore, most anticancer drugs exert their antiproliferative and cytotoxic activity via cell cycle arrest and induction of apoptosis, a controlled form of cell death that is dysregulated in cancer. Many polyadenylationtrans-acting factors, including polyadenylate polymerase (PAP), are increasingly found to be involved in cell cycle, apoptosis and cancer prognosis. The objective of the present study was to identify PAP modulations in the response of two epithelial cancer cell lines (HeLa and MCF-7) to apoptosis induction by the anticancer drugs etoposide and cordycepin. Cells were assessed for PAP activity and isoforms by the highly sensitive PAP activity assay and Western blotting, respectively. Induction of apoptosis was determined by endonucleosomal DNA cleavage, 4′6-diamidino-2-phenylindol (DAPI) staining and caspase-6 activity assay, whereas cytotoxicity and cell cycle status were assessed by trypan blue staining, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. Our results indicate that PAP changes very early in response to either etoposide or cordycepin treatment, even prior to the hallmarks of apoptosis (chromatin condensation and cleavage), in both cell lines tested, but in a different mode. Our results suggest, for the first time, that in the epithelial cancer cell lines used, PAP modulations follow cell cycle progression rather than the course of apoptosis.

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Ciprofloxacin and Levofloxacin as Potential Drugs in Genitourinary Cancer Treatment—The Effect of Dose–Response on 2D and 3D Cell Cultures

International Journal of Molecular Sciences ◽

10.3390/ijms222111970 ◽

2021 ◽

Vol 22 (21) ◽

pp. 11970

Author(s):

Tomasz Kloskowski ◽

Kamil Szeliski ◽

Zuzanna Fekner ◽

Marta Rasmus ◽

Paweł Dąbrowski ◽

...

Keyword(s):

Cell Cycle ◽

Bladder Cancer ◽

Cancer Treatment ◽

Cell Lines ◽

Cancer Cell ◽

Molecular Analysis ◽

Cytotoxic Effect ◽

Drug Repositioning ◽

Cancer Cell Lines ◽

Prostate Cell

Introduction: Introducing new drugs for clinical application is a very difficult, long, drawn-out, and costly process, which is why drug repositioning is increasingly gaining in importance. The aim of this study was to analyze the cytotoxic properties of ciprofloxacin and levofloxacin on bladder and prostate cell lines in vitro. Methods: Bladder and prostate cancer cell lines together with their non-malignant counterparts were used in this study. In order to evaluate the cytotoxic effect of both drugs on tested cell lines, MTT assay, real-time cell growth analysis, apoptosis detection, cell cycle changes, molecular analysis, and 3D cultures were examined. Results: Both fluoroquinolones exhibited a toxic effect on all of the tested cell lines. In the case of non-malignant cell lines, the cytotoxic effect was weaker, which was especially pronounced in the bladder cell line. A comparison of both fluoroquinolones showed the advantage of ciprofloxacin (lower doses of drug caused a stronger cytotoxic effect). Both fluoroquinolones led to an increase in late apoptotic cells and an inhibition of cell cycle mainly in the S phase. Molecular analysis showed changes in BAX, BCL2, TP53, and CDKN1 expression in tested cell lines following incubation with ciprofloxacin and levofloxacin. The downregulation of topoisomerase II genes (TOP2A and TOP2B) was noticed. Three-dimensional (3D) cell culture analysis confirmed the higher cytotoxic effect of tested fluoroquinolone against cancer cell lines. Conclusions: Our results suggest that both ciprofloxacin and levofloxacin may have great potential, especially in the supportive therapy of bladder cancer treatment. Taking into account the low costs of such therapy, fluoroquinolones seem to be ideal candidates for repositioning into bladder cancer therapeutics.

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