Sino-C is a Sinomenine derivative with anticancer properties. It disrupts cholesterol homeostasis by upregulating crucial genes such as SREBF2 and HMGCS1, leading to intracellular cholesterol accumulation and lipid droplet formation. The metabolic disturbance induced by Sino-C further triggers lipid peroxidation and endoplasmic reticulum (ER) stress, initiating a unique mixed form of cell death that includes both apoptotic (cleaved PARP) and necrotic-like features. Sino-C is applicable in studies of colorectal cancer, lung cancer, and breast cancer.

Sino-C (0-20 μM, 48 hours) exhibits broad-spectrum anticancer activity in colorectal cancer (HCT116, RKO, and MC38), lung cancer (A549 and NCI-H1299), and breast cancer (MDA-MB-231 and 4T1) cells. In HCT116 and RKO cells, Sino-C (0-20 μM, 24 hours) demonstrates significant anti-colorectal cancer effects. The compound induces death in HCT116 and RKO cells, characterized by PARP cleavage without caspase-3 activation, causing severe morphological changes (including nuclear periphery widening, significant endoplasmic reticulum expansion with ribosome shedding, and mitochondrial swelling) and accompanied by notable lactate dehydrogenase leakage and cell membrane damage, suggesting a non-apoptotic mechanism. Sino-C (24 h) triggers a distinctive form of cell death in HCT116 cells, showing a blend of apoptotic and necrotic features not aligning with classical apoptosis, paraptosis, pyroptosis, or ferroptosis. Furthermore, in HCT116 cells, Sino-C (0-20 μM) upregulates cholesterol homeostasis-related genes, increases intracellular cholesterol levels, and induces lipid droplet accumulation. Sino-C (0-20 μM, 24 hours) causes cholesterol imbalance, leading to lipid peroxidation, which subsequently triggers endoplasmic reticulum stress, ultimately promoting the death of colorectal cancer cells.

Sino-C, administered intraperitoneally at doses of 30 and 50 mg/kg every other day from day 14 to day 28, demonstrates significant anti-colorectal cancer activity in a BALB/c nude mouse model induced by HCT116 cells.