Table 1.

Anti-cancer effects of stigmasterol.

Cell Lines	Key Results	Ref
A2780 human ovarian cancer cell line SKOV3 human ovarian cancer cell line	A2780 cells (IC50 = 69.24 ± 7.31 for 24 h) SKOV3 cells (IC50 = 83.39 ± 3.75 for 24 h) Inhibited cell migration in A2780/SKOV3 cells Inhibited cell proliferation in A2780/SKOV3 cells Down-regulated the expression of p-PI3K/p-Akt protein levels Up-regulated the expression of PI3K/Akt/PTEN protein levels in SKOV3 cells Reduced the levels of PI3K and Akt in A2780/SKOV3cells Increased the expression of PTEN in A2780/SKOV3cells	[88]
Human gastric cancer cell line SGC-7901, MGC-803, and normal GES-1 cell line	Inhibited cell proliferation in SGC-7901/MGC-803 cells Induced apoptosis and autophagy in vitro Blocked Akt/mTOR signaling pathway Suppressed tumor growth of gastric cancer in vivo	[95]
Human ovarian cancer cells	Inhibited development of ES2 and OV90 cells Induced cell apoptosis Suppressed cell migration Inhibited angiogenesis genes Increased ROS production Increased calcium levels in the cytosol and mitochondria Increased mitochondrial depolarization Stimulated cell death Activated the ER-mitochondrial axis Inactivated PI3K and MAPK signal cascades	[87]
Human endometrial cancer cell lines, Ishikawa and SPEC2	Inhibited Nrf2/NQO1/HO1 expression in endometrial cancer cells Suppressed Nrf2-ARE activity when combined with cisplatin Enhanced early apoptosis when combined with cisplatin Inhibited Tet1 expression/Tet1-induced hydroxymethylation Enhanced the inhibitory effect of cisplatin on migration and invasion	[36]
Human breast cancer cells (MDA-MB-231) and normal (HEK-293) cell lines	IC50 = 24.5 μg/mL Induced strong cytotoxic effects on MDA-MB-231 cells Increased ROS production Activated caspase-3 and -9 Induced apoptosis in MDA-MB-231 cells Increased levels of p53, Bax, caspase-3 and -9 Declined Bcl-2 gene expression Induced MDA-MB-231 cell death via apoptotic pathway	[34]
Molecular docking simulation In silico ADMET approach Molecular targets of breast cancer: ER-α, PR, HER2, and EGFR	Inhibited molecular targets of breast cancer: PR/ER-α/EGFR/HER2 Exhibited stronger binding affinities towards PR/ER-α/EGFR/HER2 Showed hydrophobic interaction with amino acid residue of PR/ER-α/EGFR/HER2 Identified as a substrate for P-glycoprotein and CYP3A4 Demonstrated high permeability for human intestinal absorption and Caco-2 cells Showed high blood–brain barrier permeability Showed no carcinogenicity	[42]
Human breast cancer cell lines MCF7 and MDA-MB-231	Showed low cytotoxicity Significantly reduced levels of p-ERK/NF-Kb/VEGF/VEGFR-2 (p ≤ 0.05) Reduced Ki67 levels when combined with sorafenib (p ≤ 0.05) Markedly decreased VEGFR-2 mRNA gene expression Increased caspase-3 activity Decreased Bcl2 levels	[38]
Human gastric cancer cell line SNU-1, GES-1 normal cell line	IC50 = 15 µM Inhibited gastric cancer growth Inducted mitochondrial-mediated apoptosis Inhibited cancer cell migration Induced cell apoptosis Triggered G2/M cell cycle arrest in a dose-dependent manner Inhibited the JAK/STAT signalling pathway Exhibited minimal anticancer effects on the normal GES-1 cells Suppressed the phosphorylation of pSTAT1/pSTAT 2/pJAK1/pJAk2	[89]
Lung cancer cell lines	Inhibited the proliferation Promoted the apoptosis Modulated retinoic acid-related orphan receptor C (RORC) Increased levels of caspase-3 and caspase-9	[31]
Human hepatoma HepG2 cells	Showed potent cytotoxicity against HepG2 cells in a dose-dependent manner Up-regulated the levels of Bax, p53 Down-regulated the levels of Bcl-2 Induced apoptosis: caspase-8, 9 Increased apoptotic cell numbers Induced morphological changes Induced DNA damage	[32]
DMBA croton oil induced skin carcinoma	Reduced tumor size and cumulative number of papillomas Significantly increased the average latency period Decreased the levels of ASAT/ALAT/ALP Significantly increased glutathione (GSH)/superoxide dismutase (SOD)/catalase (CAT) Significantly inhibited high levels of lipid peroxide and DNA damage	[20]
Human gall bladder cancer cells	Up-regulated p27 expression gene Down-regulated Jab1 expression gene Activated caspase-3 Induced apoptosis Increased apoptotic cells and DNA	[92]
Ehrlich Ascites Carcinoma mice	Decreased tumor volume Decreased packed cell volume and viable cell count Increased mean survival time Increased life span of EAC tumor bearing mice Decreased the levels of lipid peroxidation Increased the levels of GSH/SOD/CAT Increased LDH activity in ascitic fluid Decreased membrane microviscosity Activated protein phosphatase 2A by ceramide Protected the heamoto-poietic system Increased the hemoglobin content/RBC count Reduced WBC count Increased platelet count	[93]
Human umbilical vein endothelial cells (HUVECs) Human cholangiocarcinoma (CCA) cells	IC50 = 21.1 ± 2.1 μM Suppressed cell viability, migration, and morphogenesis on HUVECs, but not CCA cells Significantly reduced the transcript level of TNF-α Decreased levels of VEGFR-2/Src/Akt/PCL/FAK Disrupted tumor angiogenesis (in vivo) Reduced the growth of CCA cells (in vivo) Decreased CD31-positive vessel content Decreased macrophage recruitment	[41]
HeLa cervical cancer cells	IC50 = 26.42 µM Exhibited cytotoxic effects Reduced cell viability	[35]
Human prostate cancer cells DU-145	Inhibited prostate cancer growth Increased p53 protein expression Inhibited carcinoma development Decreased p21 and p27 protein expression	[94]
Molecular docking In silico Approach (ADMET screening) Human papillomavirus type (HPV-18 E1) protein (PDB ID: 1R9W) MD simulations	Showed high binding affinity: docking score of −8.7 kJ/mol Inhibited HPV-18 (1R9W protein) Showed high stability inside the binding pocket of 1R9W	[40]
Cervical cancer cells (HeLa) and Vero cells (L-929) In silico molecular docking	HeLa cells: IC50 = 11.58 µg/mL Vero cells: IC50 = 173.8 µg/mL Showed great in silico molecular docking activity Exhibited in vitro anticancer activity Exhibited potent cytotoxic activity at a concentration of 100 μg/mL Strongly occupied the active location of 3F81 Exhibited substantial interaction energy values against the protein target vaccinia H1-related (VHR) phosphatise Reduced the proliferation of cervical cancer cells (RCSB PDB ID: 3F81)	[7]