Table 2.

The ROS-overloading strategies in cancer control

Categories	Drug names	Mechanism	ROS	Effects	Tumors	References
ATF-6 inhibitors	Melatonin	RET induction	Increase	Anti-tumor	Head and neck squamous cell carcinoma	[405]
Complex I inhibitors	SMIP003	Complex I Q site inhibition	Increase	Anti-tumor	Triple-negative breast cancer	[406]
	Metformin	Complex I FMN site inhibition	Decrease	Anti-tumor	Colon cancer	[407]
	Phenformin	Complex I inhibition	Increase	Anti-tumor	Brain tumors	[408]
					Melanoma, breast, colon, lung, and prostate cancer	[409]
	Carboxyamidotriazole	Complex I inhibition	Increase	Anti-tumor	Colon cancer	[410]
DNA cross-linking agent	Cisplatin	MtDNA damage	Increase	Anti-tumor	Prostate cancer	[411]
		Mitochondrial content elevation	Increase	Anti-tumor	Ovarian cancer	[412]
​PML-RARα inhibitors	Arsenic trioxide	GSH depletion	Increase	Anti-tumor	Leukemia	[413]
		Complex IV inhibition	Increase	Anti-tumor	Leukemia	[414]
		TrxR and Prx inhibition	Increase	Anti-tumor	Breast cancer	[415]
Topoisomerase inhibitors	DOX	NADPH-to-DOX electron transfer	Increase	Anti-tumor	Breast cancer	[416]
		NOX indirect activation			Human osteosarcoma	[417]
					Leukemia	[418]
Nanoparticles	PTX@TPGS-PBTE NPs	ROS-targeted PTX delivery	Utilize ROS	Anti-tumor	Head and neck cancer	[419]
	Nanoparticles (CPT-Pt (IV) combined with P1 and mPEG2K-DSPE)	ROS-mediated cisplatin/camptothecin release	Utilize ROS	Anti-tumor	Colon cancer	[420]
	MOFs	GSH depletion	Increase	Anti-tumor	Liver cancer and breast cancer	[421]
Radiation therapy		Free electron-H2O interaction	Increase	Anti-tumor		[422]
PDT		Photosensitizer irradiation-induced ROS generation​	Increase	Anti-tumor		[423]
RDT		Photosensitizer irradiation-induced ROS generation via high-energy X-ray	Increase	Anti-tumor		[424]
SDT		Sonoexcitation and ultrasonic cavitation	Increase	Anti-tumor		[425, 426]
CDT		Fenton reactions	Increase	Anti-tumor		[427]
Xc- System inhibitors	Erastin	Xc- System blockade	Increase	Anti-tumor	Osteosarcom, fibrosarcoma, and lung cancer	[428]
		Induction of VDAC opening	Increase	Anti-tumor	Lung cancer	[429]
					Fibrosarcoma, Ewing’s sarcoma, neuroblastoma, adult acute monocytic leukemia	[430]
	IKE	Xc- system blockade	Increase	Anti-tumor	Diffuse large B-cell lymphoma	[431]
	Sorafenib	Xc- system blockade	Increase	Anti-tumor	Hepatocellular carcinoma and renal cell carcinoma	[432]
Cyst(e)inases		Blood cystine depletion	Increase	Anti-tumor	Prostate carcinoma and breast cancer	[433]
GCL inhibitors	BSO	GCL inhibition	Increase Increase	Anti-tumor	Renal cancer and ovarian cancer	[434]
CYP450 inhibitors	PEITC	GSH depletion	Increase	Anti-tumor	Breast cancer	[435]
					Leukemia	[436]
					Lung, colon, and ovarian cancer	[437]
	BITC				Non-small cell lung cancer cells	[438]
NRF2 inhibitors	Brusatol	NRF2 protein expression suppression	Increase	Anti-tumor	Pancreatic cancer	[439]
	Halofuginone	Global protein translation inhibition	Increase	Anti-tumor	Lung adenocarcinoma, Oesophageal cancer	[440]
	ML385	Neh1 domain of the NRF2 protein binding	Increase	Anti-tumor	Head and neck squamous cell carcinoma cancer cell	[441]
					Breast cancer	[442]
Trx/TrxR inhibitors	PX-12	Trx inhibition	Increase	Anti-tumor	Acute myeloid leukemia	[443]
	Ethaselen	Trx inhibition	Increase	Anti-tumor	NSCLC and gastric cancer cell	[444, 445]
	Piperine	TrxR Sec residue binding	Increase	Anti-tumor	Cervical cancer, Non-small cell lung cancer, hepatocellular liver carcinoma	[446]
	MGd	TrxR-targeting capability	Increase	Anti-tumor	Metastatic renal cell carcinoma	[447]
					Multiple myeloma	[448]
					Lymphoma	[449]
	Auranofin	TrxR-targeting capability	Increase	Anti-tumor	Human thyroid cancer cell	[450]
					Epithelial ovarian cancer cell	[451]
					Glioblastoma and NSCLC	[452]
					NSCLC	[453]
					Pancreatic cancer	[454]
					Chronic lymphocytic leukemia	[455]
Prx inhibitors	Celastrol	Prx-2 Cys172 residue binding	Increase	Anti-tumor	Gastric cancer	[456]
NQO1/GSTP1 inhibitors	5-Methyl-N-(5-nitro-thiazol-2-yl)-3-phenylisoxazole-4-carboxamide (MNPC)	NQO1 and GSTP1 active sites binding	Increase	Anti-tumor	Glioblastoma	[457]
Phenothiazinium redox cyclers	3,7-diaminophenothiazinium-based redox cyclers	Electron transfer and NQO1 substrate	Increase	Anti-tumor	Melanoma	[458]
HIF-1α inhibitors	2-methoxyestradiol	Mitochondrial membrane potential disruption	Increase	Anti-tumor	Neuroblastoma	[459]

ATF-6 activating transcription factor 6, ERT reverse electron transfer, FMN flavin mononucleotide, NADPH nicotinamide adenine dinucleotide phosphate, DOX doxorubicin, NOX nicotinamide adenine dinucleotide phosphate oxidase, PTX paclitaxel, MOFs metal–organic frameworks, PDT photodynamic therapy, RDT radiodynamic therapy, SDT sonodynamic therapy, CDT chemodynamic therapy, VDAC voltage-dependent anion channel, IKE imidazole ketone erastin, BSO buthionine sulfoximine, GCL glutamate cysteine ligase, PEITC phenethyl isothiocyanate, BITC benzyl isothiocyanate, NSCLC non-small cell lung cancer, TrxR thioredoxin reductase, MGd Motexafin Gadolinium, Prx peroxiredoxin, Cys cystatin, NQO1 NAD(P)H dehydrogenase quinone 1, GSTP1 glutathione S-transferase P1