B4 suppresses lymphoma progression by inhibiting fibroblast growth factor binding protein 1 through intrinsic...

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Lymphoma is a significant global health concern, ranking as the fifth most common cancer worldwide.
• Targeting specific cellular proteins with small molecules is a promising strategy for lymphoma treatment.
• FGFBP1 (Fibroblast Growth Factor Binding Protein 1) is implicated in cancer progression and is upregulated in various cancers, making it a potential therapeutic target.

Purpose of the Study:

• To investigate the potential of a flavonoid B4, isolated from Cajanus cajan, as an FGFBP1 inhibitor for lymphoma treatment.
• To elucidate the mechanism by which B4 affects lymphoma cell growth and progression.
• To evaluate the efficacy of B4 in preclinical lymphoma models.

Main Methods:

• In vitro studies using lymphoma cell lines to assess B4's effects on cell proliferation, apoptosis, and cell cycle.
• RNA sequencing analysis to identify genes regulated by B4 and its impact on FGFBP1 expression.
• In vivo studies using lymphoma mouse models to evaluate B4's effect on survival rates.
• Drug affinity responsive target stability (DARTS) assays to confirm B4's binding to FGFBP1.
• Experiments with patient-derived primary lymphoma cells to assess B4's efficacy.

Main Results:

• Flavonoid B4 selectively inhibited lymphoma cell growth by inducing caspase-dependent intrinsic apoptosis and G1/S phase cell cycle arrest.
• RNA sequencing confirmed that B4 inhibits FGFBP1, regulating genes involved in B-cell proliferation and DNA replication.
• B4 significantly increased the survival rate in lymphoma mouse models.
• B4 demonstrated potent inhibition of patient-derived primary lymphoma cells via FGFBP1 downregulation.
• DARTS experiments confirmed strong binding of B4 to FGFBP1, with FGFBP1 overexpression enhancing B4's sensitivity.

Conclusions:

• Flavonoid B4 acts as a novel and selective FGFBP1 inhibitor for lymphoma treatment.
• B4's mechanism involves downregulating FGFBP1, inducing intrinsic apoptosis, causing mitochondrial and DNA damage, and arresting the cell cycle.
• These findings support B4 as a potential therapeutic agent for lymphoma, highlighting its efficacy in preclinical models and patient-derived cells.