. 2020 Aug 6;21(16):5622. doi: 10.3390/ijms21165622

Table 1.

Anticancer effects of furanocoumarins in the different reported studies.

Furanocoumarins	Dietary Sources [2,3,4]	In Vitro		In Vivo		Anticancer Mechanisms	References
Furanocoumarins	Dietary Sources [2,3,4]	Cell Lines	Cytotoxic Concentration	Experimental Model	Dose	Anticancer Mechanisms	References
Angelicin	Parsnip	HeLa and SiHa	IC₃₀ = 27.8 µM; IC₅₀ = 38.2 µM	—	—	Atg3,7 and 12-5 ↑, G1/G0 arrest	[5]
		A549 (NSCLC)	IC₅₀~ 50 µmol	—	—	NF-κB inactivation G2/M phase arrest, cyclinB1 ↓, cyclin E1 ↓, and Cdc2 ↓; Bcl2 ↓; caspase 3,9 ↑, Bax↑ JNK ↑, ERK ↑; MMP2, MMP9 ↓, E-cadherin ↑	[6]
		SH-SY5Y	IC₅₀ = 49.56 μM	—	—	caspase 3,9 ↑, Bcl-2 ↓, Bcl-xL↓, and Mcl-1↓	[7]
		Caki	IC₅₀ = angelicin (50–100 μM) and TRAIL (50 ng/mL)	—	—	caspase 3↑, c-FLIP ↓	[8]
		HepG2 and Huh-7	IC50 = 90 ± 6.565 (HepG2); 60 ± 4.256 μM (Huh-7)	—	—	PI3K/Akt inhibition, Bcl-2↓	[9]
		—	—	Mouse liver xenograft model (BALB/c-nu/nu mice)	50 mg/kg (16 days)	cancer cell growth ↓; p-VEGFR ↓	[9]
Bergamottin	Carrot, cumin, dill, fig, grapefruit, lemon, lime, orange, parsley, parsnip	A549, H1299	IC₅₀ = 50–100 μM	—	—	EMT inhibition, JNK ↑; PI3K ↓, Akt↓, and mTOR kinases ↓	[10]
		U87 and U251	IC₅₀ = 2–10 μM	—	—	NF-κB inactivation, MMP9 ↓, STAT3 inhibition, Rac1 inactivation	[11]
		HT-1080	IC₅₀ = 5–50 μM	—	—	NF-κB inactivation; MMP2, MMP9↓	[12]
		HT-29 and RKO	IC₅₀ = 12.5 µM	—	—	caspase-3,8,9↑; PARP ↑; G2/M phase arrest, cyclinA ↓, cyclin B1↓, and Cdc2 ↓	[13]
		A549 (NSCLC)	IC₅₀ = 50 μM	—	—	G2/M phase arrest, cyclinA ↓, cyclin B1↓, and Cdc2 ↓	[14]
		—	—	Mouse lung xenograft model (BALB/c nude mice)	100 mg/kg (18 days)	↓ cancer cell growth	[14]
Bergapten or 5-Methoxypsoralen (5-MOP)	Anise, carrot, caraway, celeriac, celery, coriander, cumin, dill, fig, grapefruit, lemon, lime, orange, parsley, parsnip, turnip	DLD-1 and LoVo	IC₅₀ = 30 and 50 μM	—	—	G2/M phase arrest, cyclin E ↓, Cdk2 inhibition; AKT inhibition; p53 ↑, p21↑, PTEN↑	[15]
		MCF-7	IC₅₀ = 50 μM	—	—	G1-phase phase arrest, P53 ↑; AKT inhibition	[16]
		Hep-G2	IC₅₀ = 25–50 mM	—	—	G2/M phase arrest, Cdk1 inhibition	[17]
		Hep-G2	IC₅₀ = 25–100 μM	—	—	G2-M phase arrest, P53 ↑ and P21 ↑	[18]
		A549 (NSCLC)	79.1 ± 2.8% (50 μM)	—	—	G1-phase arrest, P53 ↑	[19]
		NCI-H460	74.5 ± 3.1% (50 μM)	—	—	G1-phase arrest, P53 ↑	[19]
		MCF7 and ZR-75	50 μM	—	—	PTEN ↑, Beclin1 ↑, PI3KIII ↑, UVRAG ↑, AMBRA, LC3-I to LC3-II	[20]
		HepG2	50 mM	—	—	PI3K/AKT inhibition, LXR (α and β)↑	[21]
		—	—	NDEA induced liver cancer (Wistar rats)	25 and 50 mg/kg (14 days)	↓ cancer cell growth	[21]
Bergaptol	Carrot, grapefruit, lemon, lime, parsley, parsnip	MCF-7	IC₅₀ = 52.2 µM	—	—	G1-phase arrest; caspase 3,9 ↑, Bax↑, Bcl2 ↓,MMP2 ↓, MMP9 ↓, cyt c release ↑	[22]
Byakangelicol	Lemon	HCT-15	IC₅₀ = 18.1 ± 0.3 μg·mL⁻¹	—	—	↓ cell viability	[23]
		A549 (NSCLC)	IC₅₀ =14.3 ± 0.2 μg·mL⁻¹	—	—
		SK-OV-3	IC₅₀ = 20.2 ± 0.3 μg·mL⁻¹	—	—
		SK-MEL-2	IC₅₀ = 21.2 ± 0.3 μg·mL⁻¹	—	—
		XF498	IC₅₀ = 28.4 ± 0.3 μg·mL⁻¹	—	—
Cnidicin	Lemon	HCT-15	IC₅₀ = 7.0 ± 0.2 μg·mL⁻¹	—	—	↓ cell viability	[23]
		A549 (NSCLC)	IC₅₀ = 6.8 ± 0.1 μg·mL⁻¹	—	—
		SK-OV-3	IC₅₀ = 8.8 ± 0.2 μg·mL⁻¹	—	—
		SK-MEL-2	IC₅₀ = 8.8 ± 0.2 μg·mL⁻¹	—	—
		XF498	IC₅₀ = 7.2 ± 0.3 μg·mL⁻¹	—	—
Feroniellin A	Feroniella lucida roots	A549	0.25 mM	—	—	NF-κB inactivation Atg5 ↑, Beclin1 ↑, mTOR inactivation LC3-I to LC3-II	[24]
Furanocoumarin A	Fructus liquidambaris	A549	IC₅₀ = 65.28 ± 5.36 μM	—	—	P53 ↑,Bax↑, Bcl2 ↓, caspase 3 ↑	[25]
Imperatorin	Lime, parsley	SGC-7901	IC₅₀ = 62.6 μM	—	—	promoting G1-phase arrest; PI3K/Akt/m-TOR signaling ↓	[26]
		HT-29	IC₅₀ = 78 µM	—	—	G1-phase arrest; P53 ↑ and P21 ↑; caspase 3,7 ↑; Bcl2 ↓	[27]
		HL-60	10 μM	—	—	caspase 3,9 ↑; cyt c release ↑; Bcl2 ↓, PARP cleavage	[28]
		H23	10 μg/mL	—	—	P53 ↑,Bax↑, Mcl-1↓	[29]
		HeLa	200 μM for imperatorin and 5 μM for cisplatin	—	—	Hsp27 and Hsp72 ↓,LC3 cleavage	[30]
		HCT116	150 μM			mTOR↓, p70S6K ↓, 4E-BP1↓, MAPK↓, HIF-1α inhibition	[31]
		HCT-15	IC₅₀ = 19.4 ± 0.3 μg·mL⁻¹	—	—	↓ cell viability	[23]
		A549	IC₅₀ = 16.4 ± 0.3 μg·mL⁻¹	—	—
		SK-OV-3	IC₅₀ =13.7 ± 0.3 μg·mL⁻¹	—	—
		SK-MEL-2	IC₅₀ = 14.5 ± 0.2 μg·mL⁻¹	—	—
		XF498	IC₅₀ = 12.3 ± 0.5 μg·mL⁻¹	—	—
Isoimperatorin	Lime, parsley	SGC-7901	IC₅₀ = 18.75 μg·mL⁻¹	SGC-7901 cell-induced xenograft model (mice)	10 mg/kg (20 days)	G1-phase arrest; caspase 3,9 ↑; Bax↑, Bcl2 ↓, Survivin↓	[32]
		DU145	100 µM	—	—	G1-phase arrest	[33]
		HCT-15	IC₅₀ = 5.6 ± 0.3 μg·mL⁻¹	—	—	↓ cell viability	[23]
		A549 (NSCLC)	IC₅₀ = 12.2 ± 0.4 μg·mL⁻¹	—	—
		SK-OV-3	IC₅₀ = 6.8 ± 0.3 μg·mL⁻¹	—	—
		SK-MEL-2	IC₅₀ = 9.9 ± 0.2 μg·mL⁻¹	—	—
		XF498	IC₅₀ = 10.7 ± 0.3 μg·mL⁻¹	—	—
Marmesin	Broad bean, blackberry, raspberry	U937	IC₅₀ = 40 µM	Mice	30mg/kg (30 days)	Bax↑, Bcl2 ↓, Bax/Bcl-2 ratio ↑; G2/M-phase arrest	[34]
Methoxsalen/Xanthotoxin (8-MOP)	Anise, carrot, caraway celeriac, celery, cumin, dill, grapefruit, lemon, lime, parsley, parsnip, turnip	HepG2	100 µM	—	—	Bax/Bcl-2 ratio ↑, MMP2 ↓, MMP9 ↓, ERK1/2 pathway inhibition, cyt c release ↑, AIF transposition ↑	[35]
Methoxsalen/Xanthotoxin (8-MOP)		SK-N-AS and SW620	IC₅₀ = 56.3 µM for SK-N-AS and 88.5 µM for SW620	—	—	Caspase-3,8,9↑PI3K/AKT pathway ↓, Bcl2 ↓, Bax/Bcl-2 ratio ↑	[36]
Oxypeucedanin	Lime, parsley	L5178Y (mouse T-cell lymphoma cells)	IC₅₀ = 40.33 ± 0.63 µM	—	—	caspase 3,9 ↑; cyt c release ↑; Bcl2 ↓	[37]
		HCT-15	IC₅₀ = 3.4 ± 0.3 μg·mL⁻¹	—	—	↓ cell viability	[23]
		A549 (NSCLC)	IC₅₀ = 9.5 ± 0.3 μg·mL⁻¹	—	—
		SK-OV-3	IC₅₀ = 19.3 ± 0.3 μg·mL⁻¹	—	—
		SK-MEL-2	IC₅₀ = 16.5 ± 0.2 μg·mL⁻¹	—	—
		XF498	IC₅₀ = 16.1 ± 0.5 μg·mL⁻¹	—	—
(+)-oxypeucedanin hydrate	Angelica dahurica roots	A549, HCT-15, SK-MEL-2, SK-OV-3, XF498	IC₅₀ > 30 μg·mL⁻¹	—	—
Psoralen	Carrot, celeriac, celery, cilantro, cumin, dill, fig, grapefruit, lemon, lime, parsley, parsnip	KBv200	75.3% (80 μg·mL⁻¹)	—	—	NF-κB inactivation G1/S phase arrest, c-FLIP, and IAP inhibition	[38]
		K562	92.4% (80 μg·mL⁻¹)	—	—		[38]
		MCF-7	17.32 ± 4.28% (8 μg·mL⁻¹)	—	—	G1/G0 phase arrest	[39]
		SMMC7721	40 μM	—	—	G1 phase arrest, cyclin E↓, Bax↑, Bcl2 ↓, ER stress, CHOP induction, GADD34↑, ATF4↑, GRP78↑, GRP94	[40]
		MCF-7/ADR	IC₁₀ = 8 μg/mL			P-gp efflux function inhibition	[41]
			IC₅₀ = 25.59 ± 1.74 µg/mL			P-gp ATPase activity inhibition	[42]
			43.0 µM			EMT inhibition
			107.5 µM			G0/G1 phase arrest
Sphondin	Parsnip	A549	50 μM	—	—	NF-κB inactivation	[43]
5-geranyloxy-7-methoxy-coumarin	Lime	SW480	25 µM (67%)	—	—	caspase-3,8↑; Bcl2 ↓; p38 MAPK phosphorylation inhibition; G1/G0 phase arrest	[44]

Human cancer cell lines: A549 (NSCLC), NCI-H460 (NSCLC), H23, and H1299 = lung cancer; Caki = renal carcinoma; DLD-1, LoVo, HCT-15, HT-29, HCT116, RKO, SW480 and SW620 = colorectal cancer; DU145 = prostate cancer; HL-60 = promyelocytic leukemia; HeLa and SiHa = cervical cancer; HepG2, Huh-7 and SMMC7721 = liver carcinoma; HT-1080 = fibrosarcoma; KBM-5, K562 = human chronic myeloid leukaemia; KBv200 = oral squamous carcinoma; MCF7 SKBR-3 and ZR-75 = breast cancer; SH-SY5Y and SK-N-AS = neuroblastoma; SK-MEL-2 = melanoma; SK-OV-3 = ovarian cancer; SGC-7901 = gastric cancer cell; U937 = leukemia; U87 and U251 = glioma cells; XF498 = CNS solid tumor; MCF-7/ADR = doxorubicin resistant derivatives of MCF-7 cells overexpressing P-gp; ↑ = increase; ↓ = decrease.