Bioassay-Guided Isolation of 2-[P-(2-Carboxyhydrazino)Phenoxy]-6-(Hydroxymethyl)Tetrahydro-2h-Pyran-3,4,5-Triol From Oroxylum Indicum and Investigation of Its Molecular Mechanism Action of Apoptosis Induction

Leaf crude extract (aqueous) of Oroxylum indicum (L.) Kurz induces genomic DNA fragmentation, comet formation, and inhibition of cell proliferation in prostate cancer cell line, PC3 as assessed by agarose gel electrophoresis, comet assay, and MTT assay respectively. The bioactive compound was purified through bioassay-guided fractionation using preparative HPLC and MTT as-say. The brown and water-soluble compound was characterized using 1H and 13C nuclear magnetic resonance (NMR), fourier transform infrared (FT-IR) and electrospray ionization (ESI) mass spectrometry, and the compound was iden-tified as a glycosylated hydroquinone derivative, 2-[p-(2-Carboxyhydrazino)phenoxy]-6-(hydroxymethyl) tetrahy-dro-2H-pyran-3,4,5-triol (molecular formula, C13H18N2O8; molecular mass = 330). The identified phytocompound has not been reported earlier elsewhere. Therefore, the common name of the novel anticancer phytocompound isolated from oroxylum indicum in this current study is named as oroxyquinone. The half-maximal inhibitory concentration (IC50) of oroxyquinone on PC3 cells was 19.44 µg/ml (95% CI = 17.97 to 21.04). Oroxyquinone induced cell cycle arrest at S phases and inhibition of cell migration on PC3 as assessed by flow cytome-try and wound healing assay respectively. On investigating the molecular mechanism of inducing apoptosis, the results indicated that the oroxyquinone induced apoptosis through the p38 pathway and cell cycle arrest, however, not through caspase-3 and PARP pathways. The present study identifies a novel an-ticancer molecule and provides scientific evidence supporting the therapeutic potency of OI for ethnomedicinal uses.

Download Full-text

Lipophilized Epigallocatechin Gallate Derivative Exerts Anti-Proliferation Efficacy through Induction of Cell Cycle Arrest and Apoptosis on DU145 Human Prostate Cancer Cells

Nutrients ◽

10.3390/nu12010092 ◽

2019 ◽

Vol 12 (1) ◽

pp. 92 ◽

Cited By ~ 3

Author(s):

Jun Chen ◽

Linli Zhang ◽

Changhong Li ◽

Ruochen Chen ◽

Chengmei Liu ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Epigallocatechin Gallate ◽

Human Prostate ◽

Enzymatic Esterification ◽

Cytochrome C Release ◽

Cycle Arrest ◽

13C Nuclear Magnetic Resonance ◽

Du145 Cells

Epigallocatechin gallate (EGCG) is the predominant tea polyphenol and it exhibits a hydrophilic character. The lipophilized EGCG derivative (LEGCG) was synthesized by enzymatic esterification of EGCG with lauric acid to enhance its bioactivity. The tetralauroyl EGCG was confirmed by high-performance liquid chromatography-tandem mass spectrometry and further identified as 3′, 5′, 3″, 5″-4-O-lauroyl EGCG by 1H and 13C nuclear magnetic resonance. The anti-proliferation effect of LEGCG on DU145 human prostate carcinoma cells was evaluated by MTT assay. In addition, the underlying molecular mechanism by which LEGCG exerts anti-proliferation efficacy was elucidated by flow cytometry and immunoblot analysis. Results suggested that LEGCG exhibited a dose-dependent anti-proliferation effect on DU145 cells by G0/G1 phase arrest and induction of apoptosis. LEGCG induced cell cycle arrest via p53/p21 activation, which down-regulated the cyclin D1 and CDK4 expression. In addition, LEGCG induced apoptosis by increasing the Bax/Bcl-2 ratio, the cytochrome c release, and the caspases cleavage on DU145 cells. The results provide theoretical support to prevent prostate cancer with LEGCG.

Download Full-text

Tributylphosphate (TBP) and tris (2-butoxyethyl) phosphate (TBEP) induced apoptosis and cell cycle arrest in HepG2 cells

Toxicology Research ◽

10.1039/c7tx00180k ◽

2017 ◽

Vol 6 (6) ◽

pp. 902-911 ◽

Cited By ~ 5

Author(s):

Guofa Ren ◽

Jingwen Hu ◽

Yu Shang ◽

Yufang Zhong ◽

Zhiqiang Yu ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Molecular Mechanism ◽

Hepg2 Cells ◽

Cytotoxic Effects ◽

Cycle Arrest ◽

Induced Apoptosis

The purpose of this study was to investigate the cytotoxic effects of tributylphosphate (TBP) and tris (2-butoxyethyl) phosphate (TBEP) and to explore the underlying molecular mechanism focusing on oxidative stress, apoptosis, and cell cycle arrest.

Download Full-text

Betulin Inhibits Lung Metastasis by Inducing Cell Cycle Arrest, Autophagy, and Apoptosis of Metastatic Colorectal Cancer Cells

Nutrients ◽

10.3390/nu12010066 ◽

2019 ◽

Vol 12 (1) ◽

pp. 66

Author(s):

Yo-Han Han ◽

Jeong-Geon Mun ◽

Hee Dong Jeon ◽

Ji-Ye Kee ◽

Seung-Heon Hong

Keyword(s):

Colorectal Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Lung Metastasis ◽

Therapeutic Potential ◽

Inhibitory Effect ◽

Water Soluble ◽

Mitogen Activated Protein Kinase ◽

Sw620 Cell ◽

Cycle Arrest

Background: Colorectal cancer (CRC) is one of the diseases with high prevalence and mortality worldwide. In particular, metastatic CRC shows low probability of surgery and lacks proper treatment. In this study, we conducted experiments to investigate the inhibitory effect of betulin against metastatic CRC and related mechanisms. Methods: Water-soluble tetrazolium assay was used to determine the effect of betulin on metastatic CRC cell viability. Flow cytometry and TUNEL assay were performed to confirm whether betulin can induce apoptosis, autophagy, and cell cycle arrest. A lung metastasis mouse model was employed to estimate the anti-metastatic effect of betulin. Results: betulin decreased viability of metastatic CRC cells, including CT26, HCT116, and SW620 cell lines. Through PI3K/Akt/mTOR inactivation, betulin induced AMPK-mediated G0/G1 phase arrest and autophagy of CT26 and HCT116 cells. In addition, betulin occurred caspase-dependent apoptosis via the mitogen-activated protein kinase signaling pathway in metastatic CRC cells. Moreover, orally administered betulin significantly inhibited metastasis of CT26 cells to the lung. Conclusion: Our results demonstrate the anti-metastatic effect and therapeutic potential of betulin in metastatic CRC treatment.

Download Full-text

The molecular mechanism of G2/M cell cycle arrest induced by AFB1 in the jejunum

Oncotarget ◽

10.18632/oncotarget.9594 ◽

2016 ◽

Vol 7 (24) ◽

pp. 35592-35606 ◽

Cited By ~ 22

Author(s):

Heng Yin ◽

Min Jiang ◽

Xi Peng ◽

Hengmin Cui ◽

Yi Zhou ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Molecular Mechanism ◽

M Cell ◽

Cycle Arrest

Download Full-text

Synthesis of water soluble silicon phthacyanine, naphthalocyanine bearing pyridine groups and investigation of their DNA interaction, topoisomerase inhibition, cytotoxic effects and cell cycle arrest properties

Dyes and Pigments ◽

10.1016/j.dyepig.2019.01.044 ◽

2019 ◽

Vol 164 ◽

pp. 372-383 ◽

Cited By ~ 16

Author(s):

Turgut Keleş ◽

Burak Barut ◽

Arzu Özel ◽

Zekeriya Biyiklioglu

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Dna Interaction ◽

Water Soluble ◽

Cytotoxic Effects ◽

Cycle Arrest ◽

Topoisomerase Inhibition ◽

Soluble Silicon

Download Full-text

In Vitro Anticancer Activity of Imperata cylindrica Root’s Extract toward Human Cervical Cancer and Identification of Potential Bioactive Compounds

BioMed Research International ◽

10.1155/2021/4259777 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Paul Nayim ◽

Krishna Sudhir ◽

Armelle T. Mbaveng ◽

Victor Kuete ◽

Mukherjee Sanjukta

Keyword(s):

Cell Cycle ◽

Cervical Cancer ◽

Anticancer Activity ◽

Cell Cycle Arrest ◽

Imperata Cylindrica ◽

Water Soluble ◽

High Mass ◽

Root Extract ◽

Cycle Arrest ◽

Human Cervical Cancer

Imperata cylindrica is traditionally used to cure several diseases including cancer, wounds, and hypertension. The present study was designed to investigate the anticancer activity of the methanolic root extract of I. cylindrica (IC-MeOH). The water-soluble tetrazolium-1 and colony formation assays were used to check the proliferation ability of the cells. Cell apoptosis and cell cycle were measured by flow cytometry-based fluorescence-activated cell sorting. The ultrahigh-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) analysis was used for the metabolites profiling of IC-MeOH. Based on high-mass accuracy, spectral data, and previous reports, tentative compound identifications were assigned. Our findings revealed that IC-MeOH inhibited the proliferation of HeLa and CaSki cells. The plant extract was also found to induce a concentration- and time-dependent apoptosis and cell cycle arrest in the G0/G1 phase (IC50 value) in CaSki cell line. Analysis of IC-MeOH permitted the identification of 10 compounds already reported for their anticancer activity, epicatechin, curcumin, (-)-yatein, caffeic acid, myricetin, jatrorrhizine, harmaline, cinnamaldehyde, dobutamine, and syringin. In conclusion, IC-MeOH is a rich source of cytotoxic metabolites that inhibits human cervical cancer proliferation via apoptosis and cell cycle arrest.

Download Full-text