The Effects of Ludartin on Cell Proliferation, Cell Migration, Cell Cycle Arrest and Apoptosis Are Associated with Upregulation of p21WAF1 in Saos-2 Osteosarcoma Cells In Vitro

Content Provider	Semantic Scholar
Author	Zhang, Shuang-li Li, Bao-lin Li, Wei Hua Lu, Ming De Ni, Lin-ying Ma, Hui-li Meng, Qing-gang
Copyright Year	2018
Abstract	BACKGROUND The aim of this study was investigate the effects of the sesquiterpene lactone, ludartin, on cell proliferation, cell migration, apoptosis, and the cell cycle in osteosarcoma cell lines, compared with a normal osteoblast cell line. MATERIAL AND METHODS Osteosarcoma cell lines, MG-63 Saos-2 U-2OS, T1-73 143B, and HOS, and normal hFOB 1.19 osteoblasts, were cultured and treated with increasing doses of ludartin, The MTT colorimetric assay was used to measure cell metabolic activity and viability. Apoptosis was studied by fluorescence-activated cell sorting (FACS) using 4',6-diamidino-2-phenylindole (DAPI) nuclear staining and Annexin-V/propidium iodide (PI) staining. Cell cycle was studied using flow cytometry. Cell migration and invasion were studied using wound healing and Boyden chamber assays. Protein expression was measured by Western blotting. RESULTS Ludartin inhibited cell viability, cell migration, cell proliferation, and increased cell apoptosis, in all osteosarcoma cell lines, with an IC50 dose ranging from 15-30 µM. The greatest effects were on the Saso-2 osteosarcoma cells, with an IC50 of 15 µM. However, ludartin showed minor cytotoxic effects of the normal hFOB 1.19 osteoblasts (IC50 >100 µM). Ludartin exerted its anti-proliferative effects on Saos-2 cells via induction of apoptosis and cell cycle arrest at the G2/M checkpoint, associated with reduced expression of Cdc25c (Ser216), Cdc25c, pCdc2 (Tyr15), and Cdc2 and increased expression of p21WAF1. Ludartin inhibited cell migration and invasion of the Saos-2 cells. CONCLUSIONS The dose-dependent effects of ludartin on cell proliferation, migration, apoptosis, cell cycle arrest at the G2/M checkpoint involved p21WAFI in Saos-2 osteosarcoma cells.
Starting Page	4926
Ending Page	4933
Page Count	8
File Format	PDF HTM / HTML
PubMed reference number	30008466v1
Alternate Webpage(s)	https://doi.org/10.12659/MSM.909193
DOI	10.12659/msm.909193
Journal	Medical science monitor : international medical journal of experimental and clinical research
Volume Number	24
Language	English
Access Restriction	Open
Subject Keyword	Cell Cycle Arrest Cell Cycle Checkpoints Cell Proliferation Cell Separation Cell Survival Cultured Cell Line DAPI Flow Cytometry Fluorescence Inhibitory Concentration 50 Iodides Lactones Metabolic Process, Cellular Migration, Cell Negative Regulation of Cell Cycle Neoplasms Osteoblasts Osteosarcoma of bone Positive Regulation of Apoptosis Propidium Iodide Sesquiterpene Lactone Sesquiterpenes Staining method Western Blotting cancer cell ludartin monooxyethylene trimethylolpropane tristearate
Content Type	Text
Resource Type	Article