Abstract:
:Pyruvate kinase isoenzyme M2 (PKM2) has previously been identified as a tumor biomarker and potential therapeutic target for the treatment of cancer. In the present study, FFJ-3, a structurally modified version of mollugin, an extract of the Traditional Chinese herbal medicine Rubia tinctorum (madder) was used in order to determine the anticancer activity of the compound and investigate the potential mechanisms underlying this effect in human cancer cells. The results of the present study revealed that FFJ-3 inhibited the survival of HepG2 human hepatoma cells, MCF-7 human breast cancer cells and A549 human lung adenocarcinoma cells using the MTT assay. In addition, FFJ-3 arrested cell cycle progression at G2/M and G1 in HepG2 and A549 cells, respectively. Further analyses demonstrated that FFJ-3 attenuated the expression of PKM2 protein via the inhibition of the phosphoinositide 3-kinase (PI3K)/Akt serine/threonine kinase (Akt) signaling pathway. Furthermore, treatment of all three cell types with FFJ-3 significantly increased apoptosis and decreased the mitochondrial membrane potential compared with the untreated control group. In addition, FFJ-3 treatment increased the ratio of B-cell lymphoma-2 (Bcl-2)/Bcl-2 associated X and activated the caspase-3 cascade. In conclusion, the inhibition of the PI3K/Akt signaling pathway and activation of the caspase-3 cascade by FFJ-3 were primarily responsible for the inhibition of cell proliferation and induction of apoptosis in MCF-7, HepG2 and A549 cells. The results of the present study suggest a potential therapeutic role for FFJ-3 in the treatment of human cancer.
journal_name
Oncol Lettjournal_title
Oncology lettersauthors
Li D,Wei X,Ma M,Jia H,Zhang Y,Kang W,Wang T,Shi Xdoi
10.3892/ol.2017.5761subject
Has Abstractpub_date
2017-04-01 00:00:00pages
2607-2614issue
4eissn
1792-1074issn
1792-1082pii
OL-0-0-5761journal_volume
13pub_type
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