title: Molecular mechanisms underlying the time-dependent autophagy and apoptosis induced by nutrient depletion in multiple myeloma: a pilot study.
abstract: This study explored the molecular mechanisms underlying the time-dependent autophagy and apoptosis induced by nutrient depletion in human multiple myeloma cell line RPMI8226 cells. RT-PCR and qRT-PCR were used to evaluate the transcriptional levels of Deptor, JNK1, JNK2, JNK3, Raf-1, p53, p21 and NFκB1 at 0, 6, 12, 18, 24 and 48 h after nutrient depletion in RPMI8226 cells. We found that transcriptional levels of Deptor were increased time-dependently at 0, 6, 12 and 18 h, and then decreased. Its alternation was consistent with autophagy. Transcriptional levels of Raf-1, JNK1, JNK2, p53 and p21 were increased time-dependently at 0, 6, 12, 18, 24 and 48 h accompanying with the increase of apoptosis. Transcriptional levels of NFκB1 at 6, 12, 18, 24 and 48 h were decreased as compared with 0 h. It was suggested that all the studied signaling molecules were involved in cellular response to nutrient depletion in RPMI8226 cells. Deptor contributed to autophagy in this process. Raf-1/JNK /p53/p21 pathway may be involved in apoptosis, and NFκB1 may play a possible role in inhibiting apoptosis. It remained to be studied whether Deptor was involved in both autophagy and apoptosis.
authors.affiliation: Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wen
authors.affiliation: Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. ghcui@medmail.com.cn.
authors.forename: Guohui
authors.initials: G
authors.lastname: Cui
mesh_terms: D017209:Apoptosis; D001343:Autophagy; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D009101:Multiple Myeloma / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D009748:Nutrition Disorders / Q000209:etiology* / Q000378:metabolism*; D010865:Pilot Projects; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D047908:Intracellular Signaling Peptides and Proteins; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C556139:DEPTOR protein, human; D019908:Proto-Oncogene Proteins c-raf; D058570:TOR Serine-Threonine Kinases; D048670:MAP Kinase Kinase 4