The kava chalcone flavokawain B exerts inhibitory activity and synergizes with BCL-2 inhibition in malignant B-cell lymphoma.
Phytomedicine
; 120: 155074, 2023 Nov.
Article
in En
| MEDLINE
| ID: mdl-37716033
ABSTRACT
BACKGROUND:
B-cell lymphoma, which originates from B cells at diverse differentiation stages, is the most common non-Hodgkin lymphoma with tremendous treatment challenges and unsatisfactory clinical outcomes. Flavokawain B (FKB), a naturally occurring chalcone extracted from kava, possesses promising anticancer properties. However, evidence on the effects of FKB on hematological malignancies, particularly lymphomas, remains scarce.PURPOSE:
This study aimed to investigate the antilymphoma effect of FKB and its underlying mechanisms. STUDY DESIGN/METHODS:
Proliferation assays, flow cytometry, and western blotting were employed to determine whether and how FKB affected B-cell lymphoma cell lines in vitro. Xenograft mouse models were established to evaluate the antilymphoma efficacy of FKB in vivo.RESULTS:
FKB reduced the viability of a panel of B-cell lymphoma cell lines in a dose- and time-dependent manner. Mitochondrial apoptosis was markedly induced by FKB, as evidenced by an increased percentage of annexin V-positive cells, a loss of mitochondrial membrane potential, and cleavage of caspase-3 and PARP. Moreover, FKB inhibited BCL-XL expression and synergized with the BCL-2 inhibitor ABT-199. Mechanistically, FKB treatment decreased the phosphorylation of Akt, mammalian target of rapamycin (mTOR), glycogen synthase kinase-3ß (GSK3ß), and ribosomal protein S6 (RPS6). Pharmacological blockage of phosphoinositide 3-kinase (PI3K), Akt, or GSK3ß potentiated the activity of FKB, indicating the involvement of the PI3K/Akt cascade in FKB-mediated inhibitory effects. In mouse xenograft models, the intraperitoneal administration of FKB significantly decreased lymphoma growth, accompanied by diminished mitosis and Ki-67 staining of tumor tissues.CONCLUSION:
Our data demonstrate the robust therapeutic potential of FKB in the treatment of B-cell lymphoma.Key words
Full text:
1
Database:
MEDLINE
Complementary Medicines:
Homeopatia
Main subject:
Lymphoma, B-Cell
/
Kava
/
Chalcones
Language:
En
Journal:
Phytomedicine
Year:
2023
Type:
Article
Affiliation country:
China