Synergistic effect of cryptotanshinone and temozolomide treatment against human glioblastoma cells

Abstract Glioblastoma multiforme (GBM) is a complex disease to treat owing to its profound chemoresistance. Therefore, we evaluated the combined effect and therapeutic efficacy of temozolomide (TMZ), a potent alkylating agent and the current gold standard therapy for GBM, and cryptotanshinone (CTS),...

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Main Authors: Songxian Zhu, Jingjing Guo, Li Yu, Jun Liu, Jixiang Chen, Jinxin Xin, Yuqiang Zhang, Jie Luo, Chao Duan
Format: Article
Language:English
Published: Nature Portfolio 2023-12-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-48777-z
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author Songxian Zhu
Jingjing Guo
Li Yu
Jun Liu
Jixiang Chen
Jinxin Xin
Yuqiang Zhang
Jie Luo
Chao Duan
author_facet Songxian Zhu
Jingjing Guo
Li Yu
Jun Liu
Jixiang Chen
Jinxin Xin
Yuqiang Zhang
Jie Luo
Chao Duan
author_sort Songxian Zhu
collection DOAJ
description Abstract Glioblastoma multiforme (GBM) is a complex disease to treat owing to its profound chemoresistance. Therefore, we evaluated the combined effect and therapeutic efficacy of temozolomide (TMZ), a potent alkylating agent and the current gold standard therapy for GBM, and cryptotanshinone (CTS), which inhibits glioma cell proliferation in GBM cells. Using LN229 and U87-MG human GBM cells in a short-term stimulation in vitro model, the cytotoxic and anti-proliferative effects of single and combined treatment with 4 μM CTS and 200 μM TMZ were investigated. Furthermore, cell viability, DNA damage, apoptosis rate, and signal transducer and activator of transcription 3 (STAT3) protein were measured using cytotoxic assay, comet assay, flow cytometry, and western blotting analysis, respectively. The two drugs’ synergistic interaction was validated using the synergy score. We found that the anti-proliferative effects of combination therapy using the two drugs were greater than that of each agent used alone (CTS or TMZ). Western blot analysis indicated that treatment of GBM cells with CTS combined with TMZ more significantly decreased the expression of MGMT and STAT3, than that with TMZ alone. Combined treatment with CTS and TMZ might be an effective option to overcome the chemoresistance of GBM cells in a long-term treatment strategy.
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spelling doaj.art-c85a6a1ff25c486e91fbad9f5d7bae932023-12-10T12:15:10ZengNature PortfolioScientific Reports2045-23222023-12-0113111010.1038/s41598-023-48777-zSynergistic effect of cryptotanshinone and temozolomide treatment against human glioblastoma cellsSongxian Zhu0Jingjing Guo1Li Yu2Jun Liu3Jixiang Chen4Jinxin Xin5Yuqiang Zhang6Jie Luo7Chao Duan8Brain Research Institute, Research Center of Neurological Diseases, Taihe Hospital, Hubei University of MedicineBrain Research Institute, Research Center of Neurological Diseases, Taihe Hospital, Hubei University of MedicineBrain Research Institute, Research Center of Neurological Diseases, Taihe Hospital, Hubei University of MedicineDepartment of Neurosurgery, Taihe Hospital, Hubei University of MedicineBrain Research Institute, Research Center of Neurological Diseases, Taihe Hospital, Hubei University of MedicineBrain Research Institute, Research Center of Neurological Diseases, Taihe Hospital, Hubei University of MedicineMedical Services, Taihe Hospital, Hubei University of MedicineDepartment of Neurosurgery, Taihe Hospital, Hubei University of MedicineBrain Research Institute, Research Center of Neurological Diseases, Taihe Hospital, Hubei University of MedicineAbstract Glioblastoma multiforme (GBM) is a complex disease to treat owing to its profound chemoresistance. Therefore, we evaluated the combined effect and therapeutic efficacy of temozolomide (TMZ), a potent alkylating agent and the current gold standard therapy for GBM, and cryptotanshinone (CTS), which inhibits glioma cell proliferation in GBM cells. Using LN229 and U87-MG human GBM cells in a short-term stimulation in vitro model, the cytotoxic and anti-proliferative effects of single and combined treatment with 4 μM CTS and 200 μM TMZ were investigated. Furthermore, cell viability, DNA damage, apoptosis rate, and signal transducer and activator of transcription 3 (STAT3) protein were measured using cytotoxic assay, comet assay, flow cytometry, and western blotting analysis, respectively. The two drugs’ synergistic interaction was validated using the synergy score. We found that the anti-proliferative effects of combination therapy using the two drugs were greater than that of each agent used alone (CTS or TMZ). Western blot analysis indicated that treatment of GBM cells with CTS combined with TMZ more significantly decreased the expression of MGMT and STAT3, than that with TMZ alone. Combined treatment with CTS and TMZ might be an effective option to overcome the chemoresistance of GBM cells in a long-term treatment strategy.https://doi.org/10.1038/s41598-023-48777-z
spellingShingle Songxian Zhu
Jingjing Guo
Li Yu
Jun Liu
Jixiang Chen
Jinxin Xin
Yuqiang Zhang
Jie Luo
Chao Duan
Synergistic effect of cryptotanshinone and temozolomide treatment against human glioblastoma cells
Scientific Reports
title Synergistic effect of cryptotanshinone and temozolomide treatment against human glioblastoma cells
title_full Synergistic effect of cryptotanshinone and temozolomide treatment against human glioblastoma cells
title_fullStr Synergistic effect of cryptotanshinone and temozolomide treatment against human glioblastoma cells
title_full_unstemmed Synergistic effect of cryptotanshinone and temozolomide treatment against human glioblastoma cells
title_short Synergistic effect of cryptotanshinone and temozolomide treatment against human glioblastoma cells
title_sort synergistic effect of cryptotanshinone and temozolomide treatment against human glioblastoma cells
url https://doi.org/10.1038/s41598-023-48777-z
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