PMID- 36053135
OWN - NLM
STAT- MEDLINE
DCOM- 20220907
LR  - 20220907
IS  - 1607-8454 (Electronic)
IS  - 1024-5332 (Linking)
VI  - 27
IP  - 1
DP  - 2022 Dec
TI  - Formosanin C induces autophagy-mediated apoptosis in multiple myeloma cells 
      through the PI3K/AKT/mTOR signaling pathway.
PG  - 977-986
LID - 10.1080/16078454.2022.2117126 [doi]
AB  - OBJECTIVES: Multiple myeloma (MM) is an incurable plasma cell malignancy 
      associated with poor survival. Novel therapeutic drugs are urgently needed to 
      improve MM therapy and patient outcomes. This study aimed to investigate the 
      effect of formosanin C (FC), a Chinese medicine monomer, on MM in vitro and 
      disclose the underlying molecular mechanism. METHODS: The effect of FC on the 
      viability, proliferation, apoptosis, and autophagy of MM cell lines (NCI-H929 and 
      ARP1) was studied through CCK-8, colony formation, flow cytometry, GFP-LC3, and 
      western blotting assays, respectively. A pharmacological approach and network 
      pharmacology technology were implemented to explore the potential mechanisms of 
      the action of FC on MM cells. RESULTS: FC efficiently suppressed the viability 
      and colony-forming capacity, but promoted the number of autophagic vacuoles with 
      GFP-LC3 localization and the percentage of apoptotic cells in MM cells. 
      Additionally, FC significantly increased the levels of the autophagy-related 
      proteins LC3-Ⅱ and Beclin 1, as well as the apoptosis-related proteins Bax and 
      cleaved caspase-3, but blocked the expression of the proapoptotic protein Bcl-2 
      in the cells; these effects were reversed by an inhibitor of autophagy, 
      3-methyladenine. What's more, we found that the phosphoinositide 3-kinase 
      (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling 
      pathway was involved in the FC-mediated inhibition of MM. Pharmacological 
      inhibition of this pathway dramatically relieved FC-triggered excessive 
      expression of autophagy-related proteins and rescued MM cells from FC-induced 
      apoptosis. CONCLUSION: Our findings indicate that FC exhibits an anti-MM effect 
      by activating cell autophagy through the PI3K/AKT/mTOR signaling pathway.
FAU - Chen, Ping
AU  - Chen P
AD  - Department of Hematology, Nanjing Drum Tower Hospital Clinical College of Nanjing 
      University of Chinese Medicine, Nanjing, People's Republic of China.
AD  - Department of Hematology, Nanjing Hospital of Chinese Medicine, Nanjing, People's 
      Republic of China.
FAU - Wu, Sungui
AU  - Wu S
AD  - Department of Hematology, Nanjing Drum Tower Hospital Clinical College of Nanjing 
      University of Chinese Medicine, Nanjing, People's Republic of China.
FAU - Dong, Xiaoqing
AU  - Dong X
AD  - Department of Hematology, Nanjing Drum Tower Hospital Clinical College of Nanjing 
      University of Chinese Medicine, Nanjing, People's Republic of China.
FAU - Zhou, Min
AU  - Zhou M
AD  - Department of Hematology, Nanjing Drum Tower Hospital Clinical College of Nanjing 
      University of Chinese Medicine, Nanjing, People's Republic of China.
FAU - Xu, Peipei
AU  - Xu P
AD  - Department of Hematology, Nanjing Drum Tower Hospital Clinical College of Nanjing 
      University of Chinese Medicine, Nanjing, People's Republic of China.
FAU - Chen, Bing
AU  - Chen B
AUID- ORCID: 0000-0001-8303-2531
AD  - Department of Hematology, Nanjing Drum Tower Hospital Clinical College of Nanjing 
      University of Chinese Medicine, Nanjing, People's Republic of China.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Hematology
JT  - Hematology (Amsterdam, Netherlands)
JID - 9708388
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Autophagy-Related Proteins)
RN  - 0 (Saponins)
RN  - 50773-42-7 (formosanin C)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - K49P2K8WLX (Diosgenin)
SB  - IM
MH  - Apoptosis
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - Autophagy
MH  - Autophagy-Related Proteins/pharmacology
MH  - Cell Line, Tumor
MH  - Diosgenin/analogs & derivatives
MH  - Humans
MH  - *Multiple Myeloma/drug therapy
MH  - Phosphatidylinositol 3-Kinase/metabolism/pharmacology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - *Proto-Oncogene Proteins c-akt/metabolism
MH  - Saponins
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - Formosanin C
OT  - PI3K/AKT/mTOR
OT  - apoptosis
OT  - autophagy
OT  - multiple myeloma
EDAT- 2022/09/03 06:00
MHDA- 2022/09/08 06:00
CRDT- 2022/09/02 09:32
PHST- 2022/09/02 09:32 [entrez]
PHST- 2022/09/03 06:00 [pubmed]
PHST- 2022/09/08 06:00 [medline]
AID - 10.1080/16078454.2022.2117126 [doi]
PST - ppublish
SO  - Hematology. 2022 Dec;27(1):977-986. doi: 10.1080/16078454.2022.2117126.