title: MAP30 inhibits autophagy through enhancing acetyltransferase p300 and induces apoptosis in acute myeloid leukemia cells.
abstract: Momordica anti-human immunodeficiency virus protein of 30 kDa (MAP30) has been shown to exhibit potent antitumor activities against several solid tumors. In the present investigation we demonstrated that MAP30 significantly inhibited the proliferation of acute myeloid leukemia (AML) HL-60 and THP-1 cell lines and patient AML cells through autophagy inhibition and apoptosis induction. Intriguingly, MAP30-induced cell death and apoptosis were partially rescued in combination with an autophagy activator rapamycin, and aggravated in combination with an autophagy inhibitor bafilomycin A1 in HL-60 cells, suggesting that autophagy is a pro-survival signal and its inhibition contributes to the induction of apoptosis in MAP30‑induced cell death. Further mechanism analysis demonstrated that MAP30 enhanced p300, and C646, a selective inhibitor of p300, markedly promoted autophagy and partially rescued the MAP30-induced cell death in HL-60 cells and patient AML cells. Collectively, our findings suggest that apoptosis and autophagy act cooperatively to elicit MAP30-induced cell death and MAP30 may be a potential antitumor drug candidate against AML.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325015, P.R. China.
authors.forename: Shanhu
authors.initials: S
authors.lastname: Qian
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325015, P.R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325015, P.R. China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325015, P.R. China.
authors.forename: Junqing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325015, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
authors.affiliation: Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325015, P.R. China.
authors.forename: Yixiang
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325015, P.R. China.
authors.forename: Kang
authors.initials: K
authors.lastname: Yu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325015, P.R. China.
authors.forename: Shenghui
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D001565:Benzoates / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D018942:Macrolides / Q000494:pharmacology; D029777:Momordica charantia / Q000378:metabolism; D009578:Nitrobenzenes; D010936:Plant Extracts / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D047069:Pyrazolones; D054790:Ribosome Inactivating Proteins, Type 2 / Q000494:pharmacology*; D020123:Sirolimus / Q000494:pharmacology; D050880:p300-CBP Transcription Factors / Q000037:antagonists & inhibitors; D000099224:p300-CBP-Associated Factor
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001565:Benzoates; D018942:Macrolides; D009578:Nitrobenzenes; D010936:Plant Extracts; D011720:Pyrazoles; D047069:Pyrazolones; D054790:Ribosome Inactivating Proteins, Type 2; D020123:Sirolimus; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C584509:4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid; C066347:MAP30 protein, Momordica charantia; C040929:bafilomycin A1