title: Marsdenia tenacissimae extraction (MTE) inhibits the proliferation and induces the apoptosis of human acute T cell leukemia cells through inactivating PI3K/AKT/mTOR signaling pathway via PTEN enhancement.
abstract: Marsdenia tenacissimae extraction (MTE) as a traditional Chinese herb has long been used to treat some diseases such as tumors in China. However, the potential effectiveness of MTE in leukemia has not yet been fully understood, and the related molecular mechanism is still unknown. In the present study, we aimed to evaluate the effects of MTE on the proliferation and apoptosis of Jurkat cells (T-ALL lines) and lymphocytes from T-ALL (T-cell acute lymphoblastic leukemia) patients. Firstly, CCK8 assays and flow cytometry assays revealed that MTE dose-dependently reduced the proliferation of Jurkat cells by arresting cell cycle at S phase. Secondly, Annexin V-FITC/PI-stained flow cytometry and TUNEL staining assays showed that MTE promoted the apoptosis of Jurkat cells. Mechanistically, MTE enhanced PTEN (phosphatases and tensin homolog) level and inactivated PI3K/AKT/mTOR signaling pathway in Jurkat cells, which mediated the inhibition of cell proliferation by MTE and MTE-induced apoptosis. Finally, MTE significantly inhibited the proliferation and promoted the apoptosis of lymphocytes from T-ALL patients, compared with lymphocytes from healthy peoples. Taken together, these results reveal an unrecognized function of MTE in inhibiting the proliferation and inducing the apoptosis of T-ALL cells, and identify a pathway of PTEN/PI3K/AKT/mTOR for the effects of MTE on leukemia therapy.
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.|Department of Blood Transfusion, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, 310014, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Blood Transfusion, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, 310014, China.
authors.forename: Bingyu
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Blood Transfusion, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, 310014, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, 310014, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Blood Transfusion, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, 310014, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Hao
authors.affiliation: Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, 310014, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Blood Transfusion, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, 310014, China.
authors.forename: Kaiqiang
authors.initials: K
authors.lastname: Li
authors.affiliation: Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, 310014, China.
authors.forename: Tongtong
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Blood Transfusion, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, 310014, China.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.|Institute of Neuroscience and Hypoxia Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.|Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, 310014, China.
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Tong
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019169:Jurkat Cells; D031101:Marsdenia / Q000737:chemistry; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; C546842:MTOR protein, human; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Marsdenia tenacissimae extraction; PTEN; T-cell acute lymphoblastic leukemia; apoptosis; proliferation