Table 1.

Anticancer effects of ferulic acid based on in vitro studies.

Type of Cancer	Cell Lines	Effects	Mechanisms	Concentration	References
Melanoma	Murine B16	-	↓ melanin production, ↓ tyrosinase activity, ↓ casein kinase 2 (CK2), ↑ p- tyrosinase	25 and 50 µM	[75]
	A375, CHL-1, SK-MEL-2, B16F10	Anti-angiogenic	↓ proliferation, migration and tube formation, ↓ fibroblast growth factor 1 (FGF1), ↓ FGFR1, ↓ PI3K, ↓ protein kinase B (Akt) signaling, ↓ PI3K-Akt pathway, ↑ (HUVEC) Growth, ↓ VEGF-A, FGF1, FGF2, PDGF-α, PDGF-β and phosphatidylinositol-glycan biosynthesis class f protein (PIGF)	0, 2.5, 5, 10, 20, 30, 40 μM	[43]
Sarcoma	S180	Ameliorating oxidative stress injury	↓ diosbulbin B-induced liver injury, ↓ ALT and AST activities, Ferulic acid reverses diosbulbin B-decreased CuZn-SOD and CAT enzymatic activities and mRNA expression	-	[76]
Osteosarcoma	143B and MG63	Induces apoptosis	↓ proliferation, ↑ G0/G1 phase arrest, ↓ CDK 2, CDK 4, CDK 6, ↑ Bax, ↓ Bcl-2, ↑ caspase-3 activity, ↓ PI3K/Akt activation	0,10,30,100 and 150 µM	[77]
Thyroid	TT cells	Induces apoptosis	↓ invasion, migration and colony formation, ↓ URG4/URGCP (upregulated gene-4/upregulator of cell proliferation), ↓ CCND1, CDK4, CDK6, BCL2, MMP2, and MMP9, ↑ p53, PARP, PUMA, NOXA, BAX, BID, CASP3, CASP9 and TIMP1	50, 75, 100, 150, 200, 300, 400, 500, 750 μM and 1 mM	[78]
Breast	MDA-MB 231	Induces apoptosis	↓ proliferation, ↑ apoptotic cells, ↓ percentages of cells in G0/G1 phases by TQ, ↓ in %ages of cells in the S phase by FA	Thymoquinone (TQ) and Ferulic Acid (FA) 25 μM TQ + 250 μM FA, 50 μM TQ + 350 μM FA, 50 μM TQ + 450 μM FA, 100 μM TQ + 350 μM FA, 100 μM TQ + 450 μM FA)	[79]
	MCF7 and 4T1	Induces apoptosis	↓ viability, structural changes in cancer cells as compared to normal cells, ↑ apoptosis, ↑ lipid peroxidation, ↑ mitochondrial damage, ↑ cell death	FA-Nanosponges 5, 10, 20, 40, 80, 125, 250, 500, 750, and 1000 µM	[80]
	MDA-MB-231	-	↓ S phase, ↑ antiproliferative effects, ↑ sensitivity to UV treatment	0–10 µM	[81]
	MDA-MB-231	Induces apoptosis and inhibits metastasis	↓ viability, ↑ apoptosis, ↓ metastatic potential, reversal of epithelial-mesenchymal transition (EMT), ↑ caspase-3, ↓ migration across the wound edges, ↓ migration, ↓ vimentin, ↑ E-cadherin	3, 10, 30 and 100 µM	[49]
	MCF-7, MDAMB-231 and HS578T	Induces apoptosis	↓ proliferation, ↑ cytotoxicity, ↑ p53, ↑ Bax, ↑ caspase-9	0–75 μM	[82]
Lung	A549	Induces apoptosis	↓ proliferation, ↓ oxidative stress, ↓ GSH, ↑ Keap1, ↓ Nrf2 nuclear level, ↑ apoptotic population, ↓ p-p38 MAPK level, ↓ activation of Akt/MAPK, ↓ p-STAT3, ↓ Cox-2, ↓ MMP-9 and VEGF, ↓ PECAM1, ↑ arrest at at G2/M phase, ↑ p53 and p21 protein, ↓ Cdc25C, ↑ active caspase 9,3, ↑ Bax, ↓ Bcl-2, ↑ radiation sensitivity	ferulic acid −10–400 μM, Gamma radiation 5, 7.5, 10 and 15 Gy (60 Co)	[83]
	A549	Inhibits metastasis	↓ Proliferation, ↑ G0/G1 phase (cell cycle arrest), ↓ migration and invasion, ↓ Bcl-2, ↑ Bax, ↑ Bax/Bcl-2 ratio, ↓ MMP-2 and MMP-9, ↓p- ERK and p-p38, it increased JNK expression, ↓ p-AKT, p-mTOR, p-MEK, and p-ERK	Ferulic acid derivative FXS-3 0.2–50 µM	[84]
Hepatocellular	HepG2	Induces apoptosis	↓ proliferation, ↓ oxidative stress, ↓ GSH, ↑ Keap1, ↓ Nrf2 nuclear level, ↑ apoptotic population, ↓ p-p38 MAPK level, ↓ activation of Akt/MAPK, ↓ p-STAT3, ↓ Cox-2, ↓ MMP-9 and VEGF, ↓ PECAM1, ↑ arrest at at G2/M phase, ↑ p53 and p21 protein, ↓ Cdc25C, ↑ active caspase 9,3, ↑ Bax, ↓ Bcl-2, ↑ radiation sensitivity	ferulic acid -10–400 μM, Gamma radiation 5, 7.5, 10 and 15 Gy (60 Co)	[83]
	Huh-7 and HepG2	Induces apoptosis	↓ viability, ↑ structural changes, ↑ROS, ↓ MMP, ↑ DNA damage, ↓ percent of cells in G0/G and G2/M, ↑ S phase, ↑ γH2AX, ↑ Bax, Bad, cleaved caspase 3	ZnONPs with ferulic acid (ZnONPs-FAC) 0.05, 0.1, 1, 5, 10 and 20 µg/ml	[85]
Pancreatic	MIA PaCa-2	Induces apoptosis	↓ cell viability and colony formation, ↑ p53, Bax, PTEN caspase 3 and 9	150 μM, 200 μM, 300 μM, 400 μM, 500 μM, 750 μM and 1 mM	[86]
Cervical	HeLa and Caski	Induces apoptosis	↓ viability, ↑ DNA condensation, ↑ apoptosis, ↑ pro-caspase-3, pro-caspase-8, pro-caspase-9 and PARP, ↓ Bcl-2 and Mcl-1, ↑ Bax and ROS, ↓p-Akt and p-PI3K	4–20 µM	[28]
	Hela and Caski	Induction of cell cycle arrest and autophagy	↓ invasion, ↓ MMP-9, ↑ arrest in G0/G1 phase, ↑ p53 and p21, ↓ Cyclin D1 and Cyclin E, ↓ LC3-II, Beclin1 and Atg12-Atg5	0, 0.5, 1.0,1.5 and 2.0 mM	[32]
	HeLa	-	↓ Cell viability	ferulic acid nanohybrids 1, 5, 10, 20, 30, 40, and 50 μM	[87]
	HeLa and ME-180	Enhances radiation effects by increasing lipid peroxidative markers	↓ viability ↓ GSH, ↑ TBARS, CD and LHO, ↓ SOD, CAT and GPx, ↑ DNA damage, ↑ intracellular ROS levels (results by ferulic acid + irradiation in comparison with radiation or ferulic acid treatment alone)	ferulic acid (1, 5, 10, 20, 30 and 40 µg/mL) + radiation (2, 4, 6, 8, 10, 12 and 15 Gy)	[88]
Prostate	PC-3	Induces apoptosis	↓ proliferation, ↑ ATR, ATM, CDKN1A, CDKN1B, E2F4, RB1, and TP53 (Gene expression), ↓ CCND1, CCND2, CCND3, CDK2, CDK4, and CDK6 (gene expression) ↓ CDK4 and BCL2 (protein expression), ↓ invasion and colony formation	20, 30, 50, 75, 100, 150, 200, 250, 300, 350, 500, 750, 900 µM, 1, 2 mM	[25]
	LNCaP	Induces apoptosis	↓ proliferation, ↑ CASP1, CASP2, CASP8, CYCS, FAS, FASLG, and TRADD (gene expression), ↓ BCL2 and XIAP (gene expression), ↓CDK4 and BCL2 (protein expression), ↓ invasion and colony formation	20, 30, 50, 75, 100, 150, 200, 250, 300, 350, 500, 750, 900, 1000 and 2000 µM	[25]
Colorectal	HCT- 116 and HT-29	Induces apoptosis	↑ antiproliferative effects, ↑ arrest at the G1 phase, ↓ S phase, ↑ Early apoptotic cells, ↑ Caspase 3, 8, and 9 activity	0,0.25,0.5,1.0 and 1.5 mM	[89]
	HCT116	Induces apoptosis	↓ proliferation, ↑ p15 (mRNA level)	Ferulic acid-bound resveratrol- 0, 0.625, 1.25, 2.5, 5, 10 and 20 µM	[90]