. 2012 Jun 1;16(11):1295–1322. doi: 10.1089/ars.2011.4414

Table 2.

Role of Reactive Oxygen Species in Tumor Cell Death

ROS	Source	Cancer type	Molecular target	Reference
Induction of cell death
In vitro studies
H₂O₂	Exogenous	Lymphoma	Capase-3 ↑^a	(114)
	Exogenous	Bladder	MEK1/2 ↑^a, ERK1/2 ↑^a	(59)
			Caspase-3 ↑^a, Caspase-7 ↑^a
	Apigenin	Hepatoma	Catalase ↓	(310)
	PDT	Leukemia	Caspase 3 ↑^a	(248)
	Melatonin	Leukemia	Caspase-3 ↑^a, Caspase-8 ↑^a	(28)
			Caspase-9 ↑^a
	PL	Osteosarcoma, breast, bladder, lung	Bcl-2 ↓, Survivin ↓, XIAP ↓	(252)
NO	PL	Osteosarcoma, Breast, Bladder, Lung	Bcl-2 ↓, Survivin ↓, XIAP ↓	(252)
ROS	Bortezomib	Gastric	NF-κB ↓^b, JNK ↑^a	(228)
	Orthovanadate	Thyroid	mTOR ↑^a, PI3K/AKT ↑^a, Caspase-3 ↑^a	(102)
	Bufalin	Colon	JNK ↑^a, ATG5 ↑, Beclin-1 ↑	(336)
	Capsaicin	Colon	Caspase-3 ↑^a, Caspase-8 ↑^a,	(198)
			Caspase-9 ↑^a, Bax ↑, Bcl-2 ↓
	Eugenol	Colon	p53 ↑, Caspase-3 ↑	(142)
	Cantharidin	Bladder	Caspase-3 ↑^a, Caspase-8 ↑^a,	(172)
			Caspase-9 ↑^a, Bax ↑, Bcl-2 ↓
	GA	Bladder	p-p53 ↑	(188)
	Cajanol	Breast	Caspase-3 ↑^a, Caspase-9 ↑^a	(202)
			Bax ↑, Bcl-2 ↓
	Ginseng	Breast	COX-2 ↓, PGE-2 ↓	(155)
	BITC	Osteosarcoma	Caspase-3 ↑^a, Caspase-9 ↑^a	(331)
	PEITC	Osteosarcoma	Caspase-3 ↑^a, Caspase-9 ↑^a	(331)
	Selenite	Osteosarcoma	Caspase-3 ↑^a, Bcl-2 ↓	(52)
			p53 ↑, PTEN ↑
	ABITC	Endometrial	Caspase-8 ↑^a, JNK ↑^a, SAPK ↑^a	(123)
	Garcinol	Hepatocellular	Bax ↑, Bcl-2 ↓, Caspase-3 ↑^a	(55)
			Caspase-8 ↑^a, Caspase-9 ↑^a
	Casticin	Cervical	Caspase-3 ↑^a, Caspase-9 ↑^a, Bax ↑	(49)
			Bcl-xL ↓, XIAP ↓
	Deltonin	Multiple	Bcl-2 ↓; Bax ↑, Caspase-3 ↑^a	(282)
			Caspase-9 ↑^a, AKT ↑^a, MAPK ↑^a
	Pipoxolan	Leukemia	Bcl-2 ↓, Bcl-xL ↓, MiMP ↓, Bax ↑	(54)
	ESB	Leukemia	Caspase-3 ↑^a, Caspase-9 ↑^a	(6)
	UDCA	Gastric	DR5 ↑, PKC-δ ↑^a, Caspase-3 ↑^a	(185)
			Caspase-6 ↑^a, Caspase-8 ↑^a
	Carnosic Acid	Neuroblastoma	Bcl-2 ↓, Caspase-3 ↑^a, Caspase-9 ↑^a	(303)
	Withaferin A	Melanoma	Bcl-2 ↓, Bax↑, Bim↑, Caspase-3 ↑^a	(215)
	Caspase-9 ↑^a
	EGCG	Chondrosarcoma	Bax ↑, Bak ↑, Bcl-2 ↓, Bcl-xL ↓	(343)
	Thymoquinone	Lymphoma	Caspase-3 ↑^a, Caspase-9 ↑^a, DR5 ↑	(130)
	Progesterone	Ovarian/Endometrial	p53 ↑, Bax ↑, Bcl-2 ↓	(231)
	Danthron	Gastric	Caspase-3 ↑^a, Caspase-8 ↑^a	(58)
			Caspase-9 ↑^a, Bax ↑, Bcl-2 ↓
	Tricetin	Liver	DR5 ↑	(126)
In vivo studies
H₂O₂	PL	Breast, Bladder, Lung	Bcl-2 ↓, Survivin ↓, XIAP ↓	(252)
NO	PL	Breast	Bcl-2 ↓, Survivin ↓, XIAP ↓	(252)
ROS	CHL	Leukemia	Caspase-8 ↑^a, Caspase-9 ↑^a, MiMP ↓	(254)
	AGL	Lymphoma	Caspase-3 ↑^a, Caspase-8 ↑^a	(341)
			Caspase-9 ↑^a
	DMAPT	Prostate	NF-κB ↓, JNK ↑, TRAF2 ↓,	(276)
			Caspase-8 ↑^a, XIAP ↓
Inhibition of cell death
ROS	Endogenous	Prostate	ND	(41)
	IGF-I	Pancreatic	JAK2 ↑^a	(178)

ND, not determined; ↑^a, activation; ↓^b, inactivation; ↓, down-regulation; ↑, up-regulation.

ABITC, abietyl isothiocyanate; AGL, andrographolide; AKT, AKT8 virus oncogene cellular homolog; ATG5, autophagy protein 5; Bak, Bcl-2 homologous antagonist/killer; Bax, Bcl-2-associated X protein; Bcl-2, B-cell lymphoma-2; Bcl-xL, B-cell lymphoma-extra large; Bim, Bcl-2-interacting mediator; BITC, benzyl isothiocyanate; CHL, chlorogenic acid; COX-2, cyclooxygenase-2; DMAPT, dimethylaminoparthenolide; DR5, death receptor 5; EGCG, epigallocatechin gallate; ERK1/2, extracellular signal-regulated kinase 1/2; ESB, erythrina suberosa stem bark; GA, 18 β-glycyrrhetinic acid; H₂O₂, hydrogen peroxide; IGF-I, insulin-like growth factor-1; JAK2, janus kinase 2; JNK, c-jun N-terminal kinase; MAPK, mitogen-activated protein kinase; MEK1/2, MAPK/ERK kinase 1/2; MiMP, mitochondrial membrane potential; mTOR, mammalian target of rapamycin; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; NO, nitric oxide; PDT, photodynamic therapy; PEITC, β-phenylethylisothiocyanate; PGE-2, prostaglandin E2; PI3K, phosphoinositide 3-kinase; PKC-δ, protein kinase C-delta; PL, piperlongumine; PTEN, phosphatase and tensin homolog deleted on chromosome 10; SAPK, stress-activated protein kinase; TRAF2, TNF receptor-associated factor 2; UDCA, ursodeoxycholic acid; XIAP, X-linked inhibitor of apoptosis protein.