Table 2.

Differential cellular responses to drugs, hormones, and toxicants at atmospheric O₂ versus physioxia.

Molecule	Mechanism	Conditions	Outcomes	Reference
Drugs
resveratrol	ROS scavenger, multiple targets	PC-3 and C2C12 cells 18% or 5% O2	Differential H2O2 production, proliferation, and mitochondrial network dynamics	[107]
sulforaphane	ROS scavenger, multiple targets	bEnd.3 cells 18% or 5% O2 H/R	Attenuated reoxygenation-induced ROS production at 18% O2 but not at 5% O2	[105]
quercetin	ROS scavenger, multiple targets	human neonatal foreskin fibroblasts 18% or 4% O2	GSH depletion and loss of type I cells at 18% O2 but not at 4% O2	[110]
doxorubicin	DNA intercalating agent	HCT116, IMR90, U2OS, and MCF-7 cells 18% O2 or 5% O2	↑ apoptosis at 18% O2	[49]
acetaminophen	COX inhibitor	mouse hepatocytes 18%, 10%, or 5% O2	↑ hepatotoxicity at 18% O2 ↑ mROS and RNS production at 18% O2	[36]
		HepG2 cells 18%, 8%, or 3% O2	↓ hepatotoxicity at 18% O2 differential regulation of phase I and II enzymes	[111]
cyclophosphamide	DNA cross-linking agent	HepG2 cells 18%, 8%, or 3% O2	↓ hepatotoxicity at 18% O2	[111]
teriflunomide	pyrimidine synthesis inhibitor	SW480 and SW620 cells 18% or 10% O2	↓ proapoptotic effect at 18% O2 ↓ antiproliferative effect at 18% O2	[109]
oxaliplatin	DNA synthesis inhibitor	SW480 and SW620 cells 18% or 10% O2	↓ antiproliferative effect at 18% O2	[109]
paclitaxel	microtubule stabilizer	mouse mammary tumors 18% or 3–5% O2	↑ cytotoxicity at 18% O2	[47]
alpelisib	PI3K inhibitor	mouse mammary tumors 18% or 3–5% O2	↑ cytotoxicity at 18% O2	[47]
erlotinib	EGFR inhibitor	mouse mammary tumors 18% or 3–5% O2	↑ cytotoxicity at 18% O2	[47]
vemurafenib	BRAFV600 inhibitor	patient-derived melanoma cells 18% or 6% O2	↓ Ki-67-positive cells at 18% O2 ↓ reduction of VEGF, PCG-1α, and SLC7A11 levels at 18% O2	[37]
trametinib	MEK1/2 inhibitor	patient-derived melanoma cells 18% or 6% O2	↓ Ki-67-positive cells at 18% O2 ↓ reduction of VEGF, PCG-1α, and SLC7A11 levels at 18% O2	[37]
camptothecin	topoisomerase inhibitor	U87MG cells 18% O2 or 9% O2	↑ cytotoxicity at 18% O2	[112]
dimethyl fumarate	Nrf2 inducer	RAW 264.7 cells 18% O2 or 5% O2	↑ expression of Nrf2 targets and antioxidant response	[20]
glycolic acid	keratolytic, antioxidant	Hs68 and HaCaT cells 18% or 2% O2	Differential regulation of skin barrier and dermal network-related genes	[113]
gluconolactone	keratolytic, antioxidant	Hs68 and HaCaT cells 18% or 2% O2	Differential regulation of skin barrier and dermal network-related genes	[113]
salicylic acid	keratolytic, AMPKactivator	Hs68 and HaCaT cells 18% or 2% O2	Differential regulation of skin barrier and dermal network-related genes	[113]
Hormones
17β-estradiol	ER antagonist	C2C12 cells 18% O2 or 5% O2	Differential H2O2 production, metabolism, and mitochondrial network dynamics	[114]
Toxicants
LPS	TLR4 agonist	RAW 264.7 cells 18% O2 or 5% O2	↑ production of inflammatory mediators	[20]
rotenone	complex I inhibitor	SH-SY5Y cells 18% O2 or 5% O2	↓ cytotoxicity at 18% O2 No inhibition of ATP synthesis with 0.2 µM rotenone at 18% O2 (with effects observed at 5%)	[115]
acrolein	DNA and protein adduct inducer	differentiated H9c2 cells 18% O2 and 5% O2	↑ cytotoxicity at 18% O2	[116]
aflatoxin B	DNA adduct inducer	HepG2 cells 18%, 8%, or 3% O2	↓ hepatotoxicity at 18% O2	[111]
Other
V. baccifera leaf extract	Prooxidant, cytotoxic	HepG2 cells 18% O2 or 8% O2	↑ cytotoxicity at 18% O2	[117]
CuO NPs	Prooxidant, genotoxic, cytotoxic	A549 cells 18% O2 or 13% O2	↓ NP-induced oxidative stress at 18% O2 ↓ cytotoxicity at 18% O2	[108]

Abbreviations: AMPK, AMP-dependent kinase; BRAF^V600, B-raf (mutated); COX, cyclooxygenase; EGFR, epidermal growth factor receptor; ER, estrogen receptor; GSH, reduced glutathione; H/R, hypoxia/reoxygenation; LPS, lipopolysaccharide; MEK1/2, MAPK/ERK kinase 1/2; NPs, nanoparticles; PI3K, phosphatidylinositol 3-kinase; ROS, reactive oxygen species; mROS, mitochondrial ROS; RNS, reactive nitrogen species, TLR4, toll-like receptor 4.