Table 1 Ferroptosis inducers targeting sarcoma cells and other cells

① Ferroptosis inducers in sarcoma

 5-aminolevulinic acid (ALA)

HMOX1 overexpression,

iron and lipid peroxides overload

Fe²⁺ ↑, GPX4 ↓, ROS ↑, MDA ↑

SW872 (liposarcoma), MG63 (osteosarcoma)

[144]

 ACXT-3102

SLC7A11 inhibitor

GSH ↓

SK-LMS-1, MG-63,

HTB-93, etc

(synovial sarcoma)

[145]

 Bavachin

Transferrin receptor ↑,

divalent metal transporter-1 ↑,

ferritin light chain ↓,

ferritin heavy chain ↓,

p53 ↑, p-STAT3 ↓,

SLC7A11 ↓, GPX4 ↓

Fe²⁺ ↑, GSH ↓, GPX4 ↓, ROS ↑,

Malondialdehyde ↑,

mitochondrial morphology alteration

MG63, HOS (osteosarcoma)

[146]

 Buthionine-sulfoximine (BSO)

GCL inhibitor

GSH ↓

S4MH, F21

(rhabdomyosarcoma)

[147, 148]

 β-Phenethyl isothiocyanate

(PEITC)

TfR1 ↑,

FPN, FTH1, DMT1 and IRP2 ↓, GSH/GSSG and GPX4 ↓

Fe²⁺ ↑, GSH ↓, GPX4 ↓, ROS ↑

MNNG/HOS, U-2 OS,

MG-63, 143B, K7M2 (osteosarcoma)

[149, 150]

 EF24

HMOX1 overexpression

Fe²⁺ ↑, GPX4 ↓, ROS ↑, MDA ↑

U2os, Saos-2 (osteosarcoma)

[11]

 Erastin

SLC7A11 and VDAC2/3 inhibitor

GSH ↓, ROS ↑

HT1080; C2C12, RD, RH18, RH30, etc

(various sarcomas)

[6, 92, 151, 152]

 Ferric ammonium citrate (FAC)

Iron supplement

Fe²⁺ ↑

K7M2

(murine osteosarcoma)

[153]

 Ferrous ammonium sulfate (FAS)

Iron supplement

Fe²⁺ ↑

K7M2

(murine osteosarcoma)

[153]

 KDM4A

H3K9me3 demethylation in the promoter region of SLC7A11

GSH ↓

143 B, HOS

(osteosarcoma)

[154]

 MicroRNA-1287-5p

Bound to the 3'-untranslated region of GPX4

GPX4 ↓

Human osteosarcoma cells

[155]

 Pure Artemisinin/Artemisia annua L. hydroalcoholic extract

Ferritin autophagy

Fe²⁺ ↑

D-17, OSCA-8, OSCA-40

(canine osteosarcoma)

[156, 157]

 RSL3

GPX4 inhibitor

GPX4 ↓

BJ-TERT; HT1080; C2C12, RD, RH18, RH30, etc

(various sarcomas)

[92, 97, 152]

 Sorafenib

SLC7A11 inhibitor

GSH ↓

RH30, RD, RMS, etc. (rhabdomyosarcoma)

[147, 158]

 Sulfasalazine

(SAS)

SLC7A11 inhibitor

GSH ↓

K7M2

(murine osteosarcoma)

[153]

 Theaflavin-3,3'-digallate (TF3)

Down-regulating FTH and GPX4, GSH consumption

Fe²⁺ ↑, GSH ↓, GPX4 ↓

ROS ↑, MDA ↑

MG63. HOS, hFOB1.19 (osteosarcoma)

[159]

 Tirapazamine

(under hypoxia)

SLC7A11 and GPX4 inhibitor;

up-regulating p53

Fe²⁺ ↑, GSH ↓, GPX4 ↓

143B, U2OS, MNNG/Hos (osteosarcoma)

[160]

 Ursolic acid

Ferritin autophagy

Fe²⁺ ↑

143 B, HOS (osteosarcoma)

[161]

 Zoledronic acid

Up-regulating POR,

down-regulating CoQ10,

HMOX1 overexpression

ROS ↑,

lipid peroxides ↑

Human osteosarcoma cells

[162, 163]

② Ferroptosis inducers in other cells

 BAY 11–7085

NFKBIA/IkBa inhibitor,

HMOX1 overexpression

Fe²⁺ ↑, GPX4 ↓, ROS ↑, MDA ↑

MDA-MB-231, MCF-7, MDA-MB-468, SKBR3

[164]

 BAY 87–2243

Mitochondrial complex I inhibitor

Mitochondrial membrane potential ↓, ROS ↑

G361, SK-MEL-28

[165]

 Cyst(e)inase

Cyst(e)ine consumption

GSH ↓

AsPC-1, PANC-1, BxPC-3, S2-013;

PCa cells, FVB/N mice

[48, 166]

 FeCl2

Iron supplement

Fe²⁺ ↑

OHSCs

[167]

 FIN56

GPX4 consumption and depleting CoQ10 via the mevalonate pathway

GPX4 ↓, CoQ10 ↓,

ROS ↑

BJeLR, HT-1080, MEFs, PACN1

[61, 168]

 FINO2

Indirect inhibitor of GPX4 and direct oxidant of iron

Fe²⁺ ↑, GPX4 ↓

HT-1080

[169]

 Glutamate

SLC7A11 inhibitor

GSH ↓

HT1080, PC12

[170]

 Hemin

HMOX1 overexpression and iron supplement

Fe²⁺ ↑, GPX4 ↓, ROS ↑, MDA ↑

IMR-32, SK-N-SH;

male Swiss albino mice

[23, 171]

 Hemoglobin

Iron supplement and

ROS production

Fe²⁺ ↑, ROS ↑, MDA ↑

OHSCs

[167]

 (NH4)2Fe(SO4)2

Iron supplement

Fe²⁺ ↑

IMR-32

[171]

 Piperazine erastin

SLC7A11 inhibitor

GSH ↓

HT-1080, BJeLR

[6, 97]

 Statins (fluvastatin, lovastatin, simvastatin)

HMG-CoA reductase inhibitor and GPX4 biosynthesis suppression

GPX4 ↓, CoQ10 ↓,

ROS ↑

HT-1080, HCC4006

[61, 111]