Under hypoxic conditions, rhein has also been shown to enhance cytotoxicity in colorectal cancer cells (CRC) by modulating the expression of hypoxia-inducible factor-1 alpha (HIF-1α) expression, which acts on immunosuppressive molecules such as the downstream elements programmed cell death ligand-1 (PD-L1), vascular endothelial growth factor (VEGF), cyclooxygenase 2 (COX-2) and galectin-1 [98]. Here, HIF1A is linked to colorectal carcinoma.