PMID- 33057993 OWN - NLM STAT- MEDLINE DCOM- 20210602 LR - 20210602 IS - 1573-4978 (Electronic) IS - 0301-4851 (Linking) VI - 47 IP - 11 DP - 2020 Nov TI - Chromosomal instability reducing effect of paclitaxel and lapatinib in mouse embryonic stem cells with chromosomal abnormality. PG - 8605-8614 LID - 10.1007/s11033-020-05903-8 [doi] AB - Chromosomal abnormalities, as a frequent phenomenon in cultured embryonic stem cells (ESCs), is a major obstacle in the ESC application in regenerative medicine. Recent studies showed that aneuploid embryonic stem cells of humans and mice are more vulnerable to anticancer drugs, compared with normal cells. The aim of the current study was to evaluate effects of three anticancer drugs, paclitaxel, lapatinib and bortezomib, on mouse embryonic stem cells (mESCs) as a suitable and available model. To assess in vitro cell toxicity, two mESC lines were treated with the aforementioned drugs. Using G-band karyotyping and micronucleus assay, the effect of anticancer drugs in terms of reduction of chromosomal instability in the mESCs was evaluated in control and treatment groups. Also, apoptosis rate of both groups was estimated by FITC-Annexin V/Propidium Iodide (PI) double staining. In addition, the effect of these three drugs in maintaining the pluripotency was assessed through alkaline phosphatase assay and quantification of the expression of three key pluripotency genes, Nanog, Pou5f1 and Sox-2 was performed using Real Time PCR. The rate of numerical abnormalities after treatment with paclitaxel and lapatinib was lower than the control group. The expression level of pluripotency genes exhibited no significant difference between control and treatment groups. Administration of paclitaxel and lapatinib to the mESCs culture at an appropriate dose and in a timely manner could decrease chromosome stability without affecting pluripotency. FAU - Mirzaei-Seresht, Banafsheh AU - Mirzaei-Seresht B AUID- ORCID: 0000-0002-7823-1242 AD - Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, No. 2, Hafez St., Banihashem St., Resalat Highway, P.O.Box:16635-148, Tehran, Iran. AD - Department of Genetics, Faculty of Biological Science, Shahid Beheshti University, Tehran, Iran. FAU - Bazrgar, Masood AU - Bazrgar M AUID- ORCID: 0000-0002-5453-9576 AD - Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, No. 2, Hafez St., Banihashem St., Resalat Highway, P.O.Box:16635-148, Tehran, Iran. mbazrgar@royaninstitute.org. FAU - Sheidai, Masoud AU - Sheidai M AD - Department of Genetics, Faculty of Biological Science, Shahid Beheshti University, Tehran, Iran. FAU - Hassani, Seyedeh-Nafiseh AU - Hassani SN AUID- ORCID: 0000-0001-5047-8406 AD - Department of Stem Cell and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. FAU - Masoudi, Najmeh Sadat AU - Masoudi NS AUID- ORCID: 0000-0002-6337-6625 AD - Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, No. 2, Hafez St., Banihashem St., Resalat Highway, P.O.Box:16635-148, Tehran, Iran. FAU - Mollammohammadi, Sepideh AU - Mollammohammadi S AUID- ORCID: 0000-0003-3389-8833 AD - Department of Stem Cell and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. LA - eng PT - Journal Article DEP - 20201015 PL - Netherlands TA - Mol Biol Rep JT - Molecular biology reports JID - 0403234 RN - 0 (Antineoplastic Agents) RN - 0 (Nanog Homeobox Protein) RN - 0 (Nanog protein, mouse) RN - 0 (Octamer Transcription Factor-3) RN - 0 (Pou5f1 protein, mouse) RN - 0 (SOXB1 Transcription Factors) RN - 0 (Sox2 protein, mouse) RN - 0VUA21238F (Lapatinib) RN - 69G8BD63PP (Bortezomib) RN - P88XT4IS4D (Paclitaxel) SB - IM MH - Animals MH - Antineoplastic Agents/*pharmacology MH - Apoptosis/drug effects MH - Bortezomib/pharmacology MH - Cell Line MH - Chromosomal Instability/*drug effects MH - Lapatinib/*pharmacology MH - Mice MH - Mouse Embryonic Stem Cells/*drug effects MH - Nanog Homeobox Protein/metabolism MH - Octamer Transcription Factor-3/metabolism MH - Paclitaxel/*pharmacology MH - SOXB1 Transcription Factors/metabolism OTO - NOTNLM OT - Bortezomib OT - Chromosomal instability OT - Lapatinib OT - Mouse embryonic stem cells OT - Paclitaxel EDAT- 2020/10/16 06:00 MHDA- 2021/06/03 06:00 CRDT- 2020/10/15 17:39 PHST- 2020/04/03 00:00 [received] PHST- 2020/10/07 00:00 [accepted] PHST- 2020/10/16 06:00 [pubmed] PHST- 2021/06/03 06:00 [medline] PHST- 2020/10/15 17:39 [entrez] AID - 10.1007/s11033-020-05903-8 [pii] AID - 10.1007/s11033-020-05903-8 [doi] PST - ppublish SO - Mol Biol Rep. 2020 Nov;47(11):8605-8614. doi: 10.1007/s11033-020-05903-8. Epub 2020 Oct 15.