PFKL Inhibition by DT-13: A Novel Approach to Combat Hepatocellular Carcinoma

Area of Science:

• Biochemistry
• Oncology
• Pharmacology

Background:

• Aerobic glycolysis is crucial for hepatocellular carcinoma (HCC) progression, influencing proliferation, apoptosis, immune evasion, and drug resistance.
• Targeting aerobic glycolysis presents a potential chemotherapeutic strategy for HCC.
• The effects and mechanisms of Liriope muscari Saponin C (DT-13) on HCC are currently unknown.

Purpose of the Study:

• To investigate the effects of DT-13, a compound from Liriope muscari, on HCC cells.
• To elucidate the underlying molecular mechanisms of DT-13's action in HCC.
• To evaluate DT-13's potential in combination therapy with sorafenib for HCC treatment.

Main Methods:

• In vitro and in vivo assays to assess HCC cell proliferation and apoptosis.
• Measurement of glucose consumption and lactate production to evaluate aerobic glycolysis.
• Analysis of Phosphofructokinase-1 liver (PFKL) inhibition via c-myc signaling.
• Combination therapy studies with sorafenib.

Main Results:

• DT-13 significantly inhibited HCC cell proliferation both in vitro and in vivo.
• DT-13 induced apoptosis in HCC cells.
• DT-13 treatment led to reduced glucose uptake and lactate production, indicating modulation of aerobic glycolysis.
• DT-13 was found to inhibit PFKL through c-myc signaling, affecting HCC proliferation and apoptosis.
• DT-13 enhanced the anticancer efficacy of sorafenib in HCC models.

Conclusions:

• DT-13 demonstrates potent anticancer effects against HCC by inhibiting aerobic glycolysis via PFKL and c-myc signaling.
• DT-13 induces apoptosis and reduces proliferation in HCC cells.
• DT-13 holds promise as a therapeutic agent for HCC, potentially improving outcomes when combined with existing treatments like sorafenib.