Cardamonin inhibits breast cancer growth by repressing HIF-1α-dependent metabolic reprogramming

Area of Science:

• Biochemistry
• Molecular Biology
• Cancer Research

Background:

• Cardamonin, a chalcone from Alpiniae katsumadai, exhibits anti-inflammatory and anti-tumor properties.
• The precise molecular mechanisms of cardamonin's anti-breast cancer effects are not fully understood.

Purpose of the Study:

• To elucidate the molecular mechanisms underlying cardamonin's inhibition of breast cancer progression.
• To investigate cardamonin's impact on cancer cell metabolism and related pathways.

Main Methods:

• Cell viability and apoptosis assays (CCK-8, Hoechst 33258).
• Luciferase reporter assay for hypoxia-inducible factor-1α (HIF-1α) activity.
• Measurement of glucose uptake, lactate production, and cellular metabolism (Seahorse XF96).
• Analysis of mitochondrial membrane potential, reactive oxygen species (ROS) levels, and protein expression (Western blotting, immunohistochemistry).

Main Results:

• Cardamonin suppressed MDA-MB-231 triple-negative breast cancer cell growth in vitro and in vivo.
• Inhibition of HIF-1α expression and activity via the mTOR/p70S6K pathway.
• Cardamonin promoted mitochondrial oxidative phosphorylation and ROS accumulation, while inhibiting the Nrf2-dependent ROS scavenging system.
• Reduced glycolysis, glucose uptake, and lactate production were observed, leading to ROS-induced apoptosis.

Conclusions:

• Cardamonin modulates cancer cell metabolism and inhibits breast cancer progression.
• Cardamonin demonstrates potential as a therapeutic agent for breast cancer treatment.