PMID- 32115531
OWN - NLM
STAT- MEDLINE
DCOM- 20200420
LR  - 20211204
IS  - 1347-5223 (Electronic)
IS  - 0009-2363 (Linking)
VI  - 68
IP  - 3
DP  - 2020
TI  - 11-Methoxytabersonine Induces Necroptosis with Autophagy through AMPK/mTOR and 
      JNK Pathways in Human Lung Cancer Cells.
PG  - 244-250
LID - 10.1248/cpb.c19-00851 [doi]
AB  - Aspidosperma alkaloids, a subclass of monoterpenoid indole alkaloids rich in the 
      Apocynaceae plants, possess remarkable antitumor activities, but the underlying 
      mechanisms have rarely been reported. In the current project, 
      11-methoxytabersonine (11-MT), an aspidosperma-type alkaloid isolated from 
      Tabernaemontana bovina, significantly inhibited the viability of two human lung 
      cancer cell lines A549 and H157, and the molecular mechanisms were thus 
      investigated. The results showed that 11-MT killed lung cancer cells via 
      induction of necroptosis in an apoptosis-independent manner. In addition, 11-MT 
      strongly induced autophagy in the two cell lines, which played a protective role 
      against 11-MT-induced necroptosis. Finally, the autophagy caused by 11-MT was 
      found to be via activation of the AMP activated protein kinase (AMPK)/mammalian 
      target of rapamycin (mTOR) and the c-Jun N-terminal kinase (JNK) signaling 
      pathways in both cells. Taken together, 11-MT exhibited an antitumor mechanism 
      different from that of previously reported analogues and could have the potential 
      to serve as a lead compound for the development of new chemotherapy for lung 
      cancer.
FAU - Ge, Di
AU  - Ge D
AD  - School of Biological Science and Technology, University of Jinan.
FAU - Tao, Hong-Rui
AU  - Tao HR
AD  - School of Biological Science and Technology, University of Jinan.
FAU - Fang, Lei
AU  - Fang L
AD  - School of Biological Science and Technology, University of Jinan.
FAU - Kong, Xiang-Qian
AU  - Kong XQ
AD  - Department of Vascular Surgery, Shandong Provincial Hospital affiliated to 
      Shandong University.
FAU - Han, Li-Na
AU  - Han LN
AD  - School of Biological Science and Technology, University of Jinan.
FAU - Li, Ning
AU  - Li N
AD  - School of Biological Science and Technology, University of Jinan.
FAU - Xu, Yan-Xin
AU  - Xu YX
AD  - School of Biological Science and Technology, University of Jinan.
FAU - Li, Ling-Yu
AU  - Li LY
AD  - School of Biological Science and Technology, University of Jinan.
FAU - Yu, Mei
AU  - Yu M
AD  - Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, 
      School of Life Science, Shandong University.
FAU - Zhang, Hua
AU  - Zhang H
AD  - School of Biological Science and Technology, University of Jinan.
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - Chem Pharm Bull (Tokyo)
JT  - Chemical & pharmaceutical bulletin
JID - 0377775
RN  - 0 (11-methoxytabersonine)
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Indole Alkaloids)
RN  - 0 (Monoterpenes)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - A549 Cells
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Antineoplastic Agents, Phytogenic/chemistry/isolation & 
      purification/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Screening Assays, Antitumor
MH  - Humans
MH  - Indole Alkaloids/isolation & purification/*pharmacology
MH  - Lung Neoplasms/*drug therapy/metabolism/pathology
MH  - MAP Kinase Signaling System/*drug effects
MH  - Monoterpenes/isolation & purification/*pharmacology
MH  - Necroptosis/*drug effects
MH  - Protein Kinase Inhibitors/chemistry/isolation & purification/*pharmacology
MH  - Structure-Activity Relationship
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Tabernaemontana/*chemistry
OTO - NOTNLM
OT  - 11-methoxytabersonine
OT  - antitumor
OT  - autophagy
OT  - lung cancer
OT  - necroptosis
EDAT- 2020/03/03 06:00
MHDA- 2020/04/21 06:00
CRDT- 2020/03/03 06:00
PHST- 2020/03/03 06:00 [entrez]
PHST- 2020/03/03 06:00 [pubmed]
PHST- 2020/04/21 06:00 [medline]
AID - 10.1248/cpb.c19-00851 [doi]
PST - ppublish
SO  - Chem Pharm Bull (Tokyo). 2020;68(3):244-250. doi: 10.1248/cpb.c19-00851.