The Experts below are selected from a list of 312 Experts worldwide ranked by ideXlab platform
Shuai Liu - One of the best experts on this subject based on the ideXlab platform.
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Ubenimex an apn inhibitor could serve as an anti tumor drug in rt112 and 5637 cells by operating in an akt associated manner
Molecular Medicine Reports, 2018Co-Authors: Xiaoqing Wang, Yongfei Zhang, Yang Liu, Wei Liu, Feng Guo, Lijuan Zhang, Mingyu Cui, Shuai LiuAbstract:Bladder cancer, a common urinary tract tumor, has high mortality and recurrence rates associated with metastasis. Aminopeptidase N (APN) expression and metastasis have been indicated to be associated with one another. Ubenimex may function as an APN inhibitor to inhibit the degradation of the extracellular matrix during tumorigenesis. Furthermore, APN has been widely used as an adjuvant therapy for the treatment of tumors; however, little information is available regarding the impact of Ubenimex on patients. Autophagy is suggested to be important in the transformation and progression of cancer. Additionally, apoptosis, which leads to the rapid demolition of cellular organelles and structures, has also been suggested as an important factor. Thus, the present study investigated the role of Ubenimex in inhibiting migration and invasion by downregulating APN expression levels to induce autophagic cell death and apoptosis in bladder cancer cells. RT112 and 5637 cell lines were treated with varying doses of Ubenimex. Cell viability was measured by CCK8 colorimetry and flow cytometry. Using fluorescence microscopy, autophagic cell death was assessed using acridine orange/ethidium bromide staining. Furthermore, apoptotic cell death was assessed using flow cytometry and Trypan blue staining was used to evaluate the cell death rate. Protein expression was determined by western blot analysis. Matrigel invasion assays were exploited to assess the invasion capabilities of 5637 cells. Wound‑healing migration assays and Matrigel migration assays were exploited to assess the migratory abilities of 5637 cells. Treatment with Ubenimex was accompanied by decreased Akt expression, indicating that Ubenimex may have similar functions to Akt inhibitors. Results also indicated that Ubenimex inhibited cell migration and invasion in bladder cancer cells. Furthermore, Ubenimex also induced autophagic cell death and apoptosis, which suggested that mixed programmed cell death occurred in Ubenimex‑treated bladder cancer cells. The results from the present study suggest that Ubenimex may be a potential adjuvant therapy for the treatment of bladder cancer.
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Ubenimex, an APN inhibitor, could serve as an anti‑tumor drug in RT112 and 5637 cells by operating in an Akt‑associated manner.
Molecular medicine reports, 2018Co-Authors: Xiaoqing Wang, Yongfei Zhang, Yang Liu, Wei Liu, Feng Guo, Lijuan Zhang, Mingyu Cui, Shuai LiuAbstract:Bladder cancer, a common urinary tract tumor, has high mortality and recurrence rates associated with metastasis. Aminopeptidase N (APN) expression and metastasis have been indicated to be associated with one another. Ubenimex may function as an APN inhibitor to inhibit the degradation of the extracellular matrix during tumorigenesis. Furthermore, APN has been widely used as an adjuvant therapy for the treatment of tumors; however, little information is available regarding the impact of Ubenimex on patients. Autophagy is suggested to be important in the transformation and progression of cancer. Additionally, apoptosis, which leads to the rapid demolition of cellular organelles and structures, has also been suggested as an important factor. Thus, the present study investigated the role of Ubenimex in inhibiting migration and invasion by downregulating APN expression levels to induce autophagic cell death and apoptosis in bladder cancer cells. RT112 and 5637 cell lines were treated with varying doses of Ubenimex. Cell viability was measured by CCK8 colorimetry and flow cytometry. Using fluorescence microscopy, autophagic cell death was assessed using acridine orange/ethidium bromide staining. Furthermore, apoptotic cell death was assessed using flow cytometry and Trypan blue staining was used to evaluate the cell death rate. Protein expression was determined by western blot analysis. Matrigel invasion assays were exploited to assess the invasion capabilities of 5637 cells. Wound‑healing migration assays and Matrigel migration assays were exploited to assess the migratory abilities of 5637 cells. Treatment with Ubenimex was accompanied by decreased Akt expression, indicating that Ubenimex may have similar functions to Akt inhibitors. Results also indicated that Ubenimex inhibited cell migration and invasion in bladder cancer cells. Furthermore, Ubenimex also induced autophagic cell death and apoptosis, which suggested that mixed programmed cell death occurred in Ubenimex‑treated bladder cancer cells. The results from the present study suggest that Ubenimex may be a potential adjuvant therapy for the treatment of bladder cancer.
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Autophagy flux inhibition, G2/M cell cycle arrest and apoptosis induction by Ubenimex in glioma cell lines
Oncotarget, 2017Co-Authors: Liping Han, Shuai Liu, Yongfei Zhang, Qingwei Zhao, Xianhong Liang, Prakash K Gupta, Miaoqing Zhao, Aihua WangAbstract:This study aimed to investigate whether Ubenimex could work as an anti-tumor drug alone in glioma cells and figure out the underlying potential mechanisms. Ubenimex is widely used as an adjunct therapy in multiple solid cancers. However, it is rarely used to treat glioblastoma. The function of Ubenimex in enhancing JQ1 treatment sensitivity of glioma cells by blocking autophagic degradation of HEXIM1 was previously studied. However, the detailed mechanism of autophagy regulation by Ubenimex remains unclear. The U87 and U251 cell lines were treated with different doses of Ubenimex. Cell viability was measured by using the WST-8 assay. Cell death was assessed using trypan blue staining and flow cytometry. The migration and invasive ability of glioma cells were examined by transwell migration/invasion assay. LC3-GFP-RFP was used to measure autophagic flux. Protein expression was assessed by Western blot analysis. Autophagosomes were evaluated using the transmission electron microscopy. Moreover, cell cycle arrest (PI Staining) was measured by flow cytometry. Results revealed that Ubenimex inhibited cell proliferation as well as migration/invasion in glioma cells. Besides, Ubenimex increased glioma cell death via autophagic flux inhibition. Meanwhile, Ubenimex induced G2/M phase arrest and apoptosis, and this effect was accompanied by the decreased levels of p-Akt, indicating the role of Ubenimex in the regulation of glioma cell proliferation and metastasis. To sum up, this study concluded that Ubenimex could work as an anti-tumor drug alone in the glioma cells via inhibiting autophagic flux and inducing G2/M arrest as well as apoptosis.
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autophagy flux inhibition g2 m cell cycle arrest and apoptosis induction by Ubenimex in glioma cell lines
Oncotarget, 2017Co-Authors: Liping Han, Shuai Liu, Yongfei Zhang, Qingwei Zhao, Xianhong Liang, Prakash K Gupta, Miaoqing Zhao, Aihua WangAbstract:This study aimed to investigate whether Ubenimex could work as an anti-tumor drug alone in glioma cells and figure out the underlying potential mechanisms. Ubenimex is widely used as an adjunct therapy in multiple solid cancers. However, it is rarely used to treat glioblastoma. The function of Ubenimex in enhancing JQ1 treatment sensitivity of glioma cells by blocking autophagic degradation of HEXIM1 was previously studied. However, the detailed mechanism of autophagy regulation by Ubenimex remains unclear. The U87 and U251 cell lines were treated with different doses of Ubenimex. Cell viability was measured by using the WST-8 assay. Cell death was assessed using trypan blue staining and flow cytometry. The migration and invasive ability of glioma cells were examined by transwell migration/invasion assay. LC3-GFP-RFP was used to measure autophagic flux. Protein expression was assessed by Western blot analysis. Autophagosomes were evaluated using the transmission electron microscopy. Moreover, cell cycle arrest (PI Staining) was measured by flow cytometry. Results revealed that Ubenimex inhibited cell proliferation as well as migration/invasion in glioma cells. Besides, Ubenimex increased glioma cell death via autophagic flux inhibition. Meanwhile, Ubenimex induced G2/M phase arrest and apoptosis, and this effect was accompanied by the decreased levels of p-Akt, indicating the role of Ubenimex in the regulation of glioma cell proliferation and metastasis. To sum up, this study concluded that Ubenimex could work as an anti-tumor drug alone in the glioma cells via inhibiting autophagic flux and inducing G2/M arrest as well as apoptosis.
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Ubenimex enhances Brd4 inhibition by suppressing HEXIM1 autophagic degradation and suppressing the Akt pathway in glioma cells.
Oncotarget, 2017Co-Authors: Liping Han, Qingwei Zhao, Xianhong Liang, Miaoqing Zhao, Aihua Wang, Xiaoqing Wang, Zhen Zhang, Shuai LiuAbstract:Inhibition of Brd4 by JQ1 treatment showed potential in the treatment of glioma, however, some cases showed low sensitivity of JQ1. In addition, the pre-clinical analysis showed its limitation by demonstrating that transient treatment with JQ1 leads to aggressive tumor development. Thus, an improved understanding of the mechanisms underlying JQ1 is urgently required to design strategies to improve its efficiency, as well as overcome its limitation. HEXIM1 has been confirmed to have an important role in regulating JQ1 sensitivity. In our study, Ubenimex, a classical anti-cancer drug showed potential in regulating the JQ1 sensitivity of glioma cells using the WST-1 proliferation assay. Further studies demonstrated that Ubenimex inhibited autophagy and downregulated the autophagic degradation of HEXIM1. The role of HEXIM1 in regulating JQ1 sensitivity was verified by the HEXIM1 knockdown. Since Ubenimex was verified as an Akt inhibitor, we further studied the role of Akt inhibition in regulating JQ1 sensitivity and migration of glioma cells. Data showed that Ubenimex improved the efficiency of JQ1 treatment and suppressed migration both in the in vitro and in vivo xenografts models. The Akt agonist attenuated these effects, pointing to the role of Akt inhibition in JQ1 sensitivity and suppressed migration. Our findings suggest the potential of Ubenimex adjuvant treatment to enhance JQ1 efficiency and attenuate parts of its side effect (enhancing tumor aggressive) by regulating the autophagic degradation of HEXIM1 and Akt inhibition.
Kai Fan - One of the best experts on this subject based on the ideXlab platform.
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microrna 125a attenuates the chemoresistance against Ubenimex in non small cell lung carcinoma via targeting the aminopeptidase n signaling pathway
Journal of Cellular Biochemistry, 2020Co-Authors: Wei Zhai, Li Wan, Ai Huang, Shijie Xing, Kai FanAbstract:Background Since several long noncoding RNAs (lncRNAs) have been implicated in the development of chemoresistance in non-small cell lung carcinoma (NSCLC), the aim of this study was to investigate whether antisense noncoding RNA in the INK4 locus (ANRIL) was associated with the chemoresistance of NSCLC. Method Real-time polymerase chain reaction was performed to identify potential lncRNAs involved in the chemoresistance of NSCLC, while in-silicon analyses and luciferase assays were carried out to explore the regulatory relationship among ANRIL, miR-125a, and aminopeptidase N (APN). Results Ubenimex resistant cells were associated with a high expression of ANRIL, which directly binds to miR-125a. MiR-125a directly targeted APN expression. In addition, miR-125a and ANRIL small interfering RNA inhibited the expression of APN but promoted the expression of beclin-1 and LC3, whereas ANRIL, by competing with miR-125a, promoted cell proliferation and inhibited cell apoptosis. Conclusion The data of this study suggested that, by targeting ANRIL and the APN signaling pathway, miR-125a inhibited the proliferation of NSCLC cells and promoted their apoptosis, thus attenuating the chemoresistance of NSCLC against Ubenimex.
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MicroRNA‐125a attenuates the chemoresistance against Ubenimex in non–small cell lung carcinoma via targeting the aminopeptidase N signaling pathway
Journal of cellular biochemistry, 2019Co-Authors: Wei Zhai, Li Wan, Ai Huang, Shijie Xing, Kai FanAbstract:Background Since several long noncoding RNAs (lncRNAs) have been implicated in the development of chemoresistance in non-small cell lung carcinoma (NSCLC), the aim of this study was to investigate whether antisense noncoding RNA in the INK4 locus (ANRIL) was associated with the chemoresistance of NSCLC. Method Real-time polymerase chain reaction was performed to identify potential lncRNAs involved in the chemoresistance of NSCLC, while in-silicon analyses and luciferase assays were carried out to explore the regulatory relationship among ANRIL, miR-125a, and aminopeptidase N (APN). Results Ubenimex resistant cells were associated with a high expression of ANRIL, which directly binds to miR-125a. MiR-125a directly targeted APN expression. In addition, miR-125a and ANRIL small interfering RNA inhibited the expression of APN but promoted the expression of beclin-1 and LC3, whereas ANRIL, by competing with miR-125a, promoted cell proliferation and inhibited cell apoptosis. Conclusion The data of this study suggested that, by targeting ANRIL and the APN signaling pathway, miR-125a inhibited the proliferation of NSCLC cells and promoted their apoptosis, thus attenuating the chemoresistance of NSCLC against Ubenimex.
Yingjie Zhang - One of the best experts on this subject based on the ideXlab platform.
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Synthesis and biological characterization of Ubenimex-fluorouracil conjugates for anti-cancer therapy.
European journal of medicinal chemistry, 2017Co-Authors: Yuqi Jiang, Jinning Hou, Yongxue Huang, Yuping Jia, Jian Zhang, Xuejian Wang, Qingwei Wang, Yingjie ZhangAbstract:Abstract Previously a novel Ubenimex-fluorouracil (5-FU) conjugate, BC-01 was identified and validated as a potent CD13 inhibitor with marked in vitro and in vivo antitumor potency. Herein, further structural modifications of the linker part of BC-01 was carried out to get more potent and stable Ubenimex–fluorouracil conjugates. It was striking that most of these conjugates showed even more potent CD13 inhibitory activities than BC-01 and the approved CD13 inhibitor Ubenimex. One representative compound 12a displayed significant in vitro anti-proliferation, pro-apoptosis, anti-metastasis, anti-angiogenesis and CD13+ cell elimination effects. In vitro stability and in vivo pharmacokinetic study revealed that compound 12a could release Ubenimex and 5-FU slowly, which could act as a mutual prodrug of Ubenimex and 5-FU. Compared with 5-FU or 5-FU plus Ubenimex, 12a exhibited superior in vivo antitumor growth efficiency, even in our mice model of 5-FU-resistant liver cancer. Moreover, 12a exhibited more potent in vivo anti-metastasis and lifespan extension effects compared to the approved 5-FU prodrug capecitabine. Collectively, these results suggest that further optimization and evaluation of 12a as a promising anticancer candidate are warranted to develop effective therapeutic agents for human liver cancer.
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discovery of a novel chimeric Ubenimex gemcitabine with potent oral antitumor activity
Bioorganic & Medicinal Chemistry, 2016Co-Authors: Yuqi Jiang, Jinning Hou, Yongxue Huang, Jian Zhang, Xuejian Wang, Yingjie ZhangAbstract:Herein, a novel mutual prodrug BC-A1 was discovered by integrating Ubenimex and gemcitabine into one molecule. Biological characterization revealed that compound BC-A1 could maintain both the anti-CD13 activity of Ubenimex and the cytotoxic activity of gemcitabine in vitro. Further characterization also demonstrated that compound BC-A1 exhibited significant anti-invasion and anti-angiogenesis effects in vitro. The preliminary stability test of BC-A1 revealed that it could release gemcitabine in vitro. The in vivo anti-tumor results in liver cancer showed that at the same dosage, oral administration of BC-A1 was as potent as intraperitoneal administration of gemcitabine. This warranted the further research and development of the orally active prodrug BC-A1 because gemcitabine can not be orally administrated in clinic.
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Discovery of a novel chimeric Ubenimex–gemcitabine with potent oral antitumor activity
Bioorganic & medicinal chemistry, 2016Co-Authors: Yuqi Jiang, Jinning Hou, Yongxue Huang, Jian Zhang, Xuejian Wang, Yingjie ZhangAbstract:Herein, a novel mutual prodrug BC-A1 was discovered by integrating Ubenimex and gemcitabine into one molecule. Biological characterization revealed that compound BC-A1 could maintain both the anti-CD13 activity of Ubenimex and the cytotoxic activity of gemcitabine in vitro. Further characterization also demonstrated that compound BC-A1 exhibited significant anti-invasion and anti-angiogenesis effects in vitro. The preliminary stability test of BC-A1 revealed that it could release gemcitabine in vitro. The in vivo anti-tumor results in liver cancer showed that at the same dosage, oral administration of BC-A1 was as potent as intraperitoneal administration of gemcitabine. This warranted the further research and development of the orally active prodrug BC-A1 because gemcitabine can not be orally administrated in clinic.
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Discovery of BC-01, a novel mutual prodrug (hybrid drug) of Ubenimex and fluorouracil as anticancer agent
European journal of medicinal chemistry, 2016Co-Authors: Yuqi Jiang, Jinning Hou, Yongxue Huang, Yuping Jia, Mingming Zou, Jian Zhang, Xuejian Wang, Yingjie ZhangAbstract:We designed and synthesized a novel mutual prodrug, named BC-01 (3), by integrating Ubenimex and Fluorouracil (5-FU) into one molecule based on prior research results that showed that a combination of the aminopeptidase N (CD13) inhibitor, Ubenimex, and the cytotoxic antitumor agent, 5-FU, exhibited improved in vitro and in vivo antitumor efficiency. 3 showed potent inhibitory activity against CD13 enzymatic activity. Compared with Ubenimex, 3 exhibited more potent anti-angiogenesis effects, and compared with the approved 5-FU prodrug, capecitabine, 3 exhibited more potent tumor growth inhibitory and anti-metastasis effects. Additionally, compared with 5-FU or 5-FU plus Ubenimex, 3 also exhibited a superior antitumor efficiency even in our 5-FU-resistant mice model. Other antitumor agents could be conjugated with Ubenimex using this strategy to obtain novel mutual prodrugs with promising antitumor potency.
Wei Zhai - One of the best experts on this subject based on the ideXlab platform.
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microrna 125a attenuates the chemoresistance against Ubenimex in non small cell lung carcinoma via targeting the aminopeptidase n signaling pathway
Journal of Cellular Biochemistry, 2020Co-Authors: Wei Zhai, Li Wan, Ai Huang, Shijie Xing, Kai FanAbstract:Background Since several long noncoding RNAs (lncRNAs) have been implicated in the development of chemoresistance in non-small cell lung carcinoma (NSCLC), the aim of this study was to investigate whether antisense noncoding RNA in the INK4 locus (ANRIL) was associated with the chemoresistance of NSCLC. Method Real-time polymerase chain reaction was performed to identify potential lncRNAs involved in the chemoresistance of NSCLC, while in-silicon analyses and luciferase assays were carried out to explore the regulatory relationship among ANRIL, miR-125a, and aminopeptidase N (APN). Results Ubenimex resistant cells were associated with a high expression of ANRIL, which directly binds to miR-125a. MiR-125a directly targeted APN expression. In addition, miR-125a and ANRIL small interfering RNA inhibited the expression of APN but promoted the expression of beclin-1 and LC3, whereas ANRIL, by competing with miR-125a, promoted cell proliferation and inhibited cell apoptosis. Conclusion The data of this study suggested that, by targeting ANRIL and the APN signaling pathway, miR-125a inhibited the proliferation of NSCLC cells and promoted their apoptosis, thus attenuating the chemoresistance of NSCLC against Ubenimex.
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MicroRNA‐125a attenuates the chemoresistance against Ubenimex in non–small cell lung carcinoma via targeting the aminopeptidase N signaling pathway
Journal of cellular biochemistry, 2019Co-Authors: Wei Zhai, Li Wan, Ai Huang, Shijie Xing, Kai FanAbstract:Background Since several long noncoding RNAs (lncRNAs) have been implicated in the development of chemoresistance in non-small cell lung carcinoma (NSCLC), the aim of this study was to investigate whether antisense noncoding RNA in the INK4 locus (ANRIL) was associated with the chemoresistance of NSCLC. Method Real-time polymerase chain reaction was performed to identify potential lncRNAs involved in the chemoresistance of NSCLC, while in-silicon analyses and luciferase assays were carried out to explore the regulatory relationship among ANRIL, miR-125a, and aminopeptidase N (APN). Results Ubenimex resistant cells were associated with a high expression of ANRIL, which directly binds to miR-125a. MiR-125a directly targeted APN expression. In addition, miR-125a and ANRIL small interfering RNA inhibited the expression of APN but promoted the expression of beclin-1 and LC3, whereas ANRIL, by competing with miR-125a, promoted cell proliferation and inhibited cell apoptosis. Conclusion The data of this study suggested that, by targeting ANRIL and the APN signaling pathway, miR-125a inhibited the proliferation of NSCLC cells and promoted their apoptosis, thus attenuating the chemoresistance of NSCLC against Ubenimex.
Qi Pang - One of the best experts on this subject based on the ideXlab platform.
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Ubenimex induces apoptotic and autophagic cell death in rat GH3 and MMQ cells through the ROS/ERK pathway.
Drug design development and therapy, 2019Co-Authors: Yanjun Wang, Bo Pang, Rui Zhang, Qi PangAbstract:Purpose Ubenimex, an aminopeptidase N (APN) inhibitor, is widely known for its use as an adjunct therapy for cancer therapy. However, in recent studies, it has also conferred antitumour effects in many cancers, but its anticancer mechanism is largely unknown. This study aims to investigate the specific anticancer activities and mechanisms of Ubenimex in GH3 and MMQ cells. Materials and methods In this study, we investigated the anticancer effects of Ubenimex in GH3 and MMQ cells. Cell viability and cell death were assessed by the Cell Counting Kit-8 kit (CCK-8) and a LIVE/DEAD cell imaging kit. Apoptosis and intracellular reactive oxygen species (ROS) generation were assessed by flow cytometry and fluorescence microscopy. Autophagosome formation was detected by transmission electron microscopy, and autophagic flux was measured with mRFP-GFP-LC3 adenoviral transfection. The protein expression level was detected by Western blotting. Results The results revealed that treatment with Ubenimex induced apoptotic and autophagic cell death in GH3 and MMQ cells, which resulted in decreased viability, an increased proportion of apoptotic cells, and autophagosome formation. Further experiments showed that Ubenimex induced ROS generation and activated the ROS/ERK pathway. The ROS scavenger NAC could attenuate Ubenimex-induced apoptosis and autophagy. Conclusion Our studies revealed that Ubenimex exerted anticancer effects by inducing apoptotic and autophagic cell death in GH3 and MMQ cells, rendering it a possible effective adjunctive therapy for pituitary treatment.
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Ubenimex induces apoptotic and autophagic cell death in rat gh3 and mmq cells through the ros erk pathway
Drug Design Development and Therapy, 2019Co-Authors: Yanjun Wang, Bo Pang, Rui Zhang, Qi PangAbstract:Purpose Ubenimex, an aminopeptidase N (APN) inhibitor, is widely known for its use as an adjunct therapy for cancer therapy. However, in recent studies, it has also conferred antitumour effects in many cancers, but its anticancer mechanism is largely unknown. This study aims to investigate the specific anticancer activities and mechanisms of Ubenimex in GH3 and MMQ cells. Materials and methods In this study, we investigated the anticancer effects of Ubenimex in GH3 and MMQ cells. Cell viability and cell death were assessed by the Cell Counting Kit-8 kit (CCK-8) and a LIVE/DEAD cell imaging kit. Apoptosis and intracellular reactive oxygen species (ROS) generation were assessed by flow cytometry and fluorescence microscopy. Autophagosome formation was detected by transmission electron microscopy, and autophagic flux was measured with mRFP-GFP-LC3 adenoviral transfection. The protein expression level was detected by Western blotting. Results The results revealed that treatment with Ubenimex induced apoptotic and autophagic cell death in GH3 and MMQ cells, which resulted in decreased viability, an increased proportion of apoptotic cells, and autophagosome formation. Further experiments showed that Ubenimex induced ROS generation and activated the ROS/ERK pathway. The ROS scavenger NAC could attenuate Ubenimex-induced apoptosis and autophagy. Conclusion Our studies revealed that Ubenimex exerted anticancer effects by inducing apoptotic and autophagic cell death in GH3 and MMQ cells, rendering it a possible effective adjunctive therapy for pituitary treatment.