CLOCK (Circadian Locomotor Output Cycles Kaput) is a core circadian-rhythm transcription factor with major roles in cell-cycle control, metabolism, DNA repair, and immune function — all of which influence cancer.
Increasing evidence shows that circadian disruption and altered CLOCK activity can drive tumorigenesis, progression, and therapy resistance.
In many cancers, CLOCK is overexpressed or constitutively active, leading to:
-↑ cell proliferation
-↑ resistance to apoptosis
-↑ survival pathways
-↑ stemness
Cancer stemness often correlates with: ↑ CLOCK expression
Tumor Types Where CLOCK Is Often Upregulated:
Breast, Colorectal, HCC, GBM, NSCLC, Ovarian, Prostate, Pancreatic cancer
Overexpression often correlates with:
-higher grade
-poor differentiation
-worse survival
Natural Products that may modulate CLOCK:
-Melatonin
-Resveratrol
-Curcumin
-EGCG
-Quercetin
-Berberine
-Vitamin D3
-Sulforaphane
-EPA/DHA
-Silymarin/Silibinin
-Honokiol
Indirect Modulation of CLOCK:
-Butyrate (SCFA) – HDAC inhibitor; boosts PER/Cry cycling
-Genistein (soy isoflavone) – alters CLOCK and BMAL1 methylation
-Apigenin – affects BMAL1 and PER2; suppresses cancer growth
-Luteolin – modulates CLOCK through NF-κB/IL-6 pathways