Reactive Oxygen Species and Targeted Therapy for Pancreatic Cancer

Table 2

Drugs targeted to increase ROS.

Drugs or treatment	Mechanisms	Reference
Gemcitabine	Increasing ROS activated MST1 translocated to mitochondria and formed a complex with the local protein Cyp-D induced death of pancreatic cancer cells	[76]
Eriocalyxin B	Increase the intracellular ROS levels and regulating the MAPK, NF-κB pathways	[77]
Compound 3b	Increase ROS by AKT activation promoted activation of stress kinases (p38/JNK) resulting in pancreatic cancer cell death	[68]
Artemisinin	Induce apoptosis via the generation of ROS and triggering binding of CD95L to CD95 receptor	[78]
Genipin	UCP2 inhibition triggers ROS-dependent nuclear translocation of the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH), formation of autophagosomes, and the expression of the autophagy marker LC3-II	[74]
P-V; MDC-1112	Reduce STAT3 levels in the mitochondria by preventing its translocation from the cytosol and enhanced the mitochondrial levels of ROS which triggered apoptosis	[73]
Noninvasive radiofrequency treatment	Impair the function of mitochondria in cancer cells and increased ROS production	[79]
Green 1	Increase ROS production in mitochondria	[80]
SKLB316	Decrease the mitochondrial membrane potential and induce the generation of ROS in cells	[81]
Gemcitabine	Enhance selectively the expression of CXCL8 through ROS generation and NF-κB activation	[82]
Withaferin A combined with oxaliplatin	Enhance mitochondrial dysfunction, inactivation of the PI3K/AKT pathway, and accumulation of intracellular ROS	[69]
Spiclomazine	Reduce the mitochondria membrane potential, elevated ROS, and activated caspase-3/caspase-9	[71]
Cerium oxide nanoparticles	Sensitization of pancreatic cancer cells to radiation by ROS production	[83]
Oleanolic acid	Arrests the cell cycle and induces apoptosis, possibly via ROS-mediated mitochondrial and lysosomal pathway	[84]
CDDO-Me	Enhance the production of ROS and inhibited the telomerase activity; loss of mitochondrial membrane potential and release of cytochrome c from mitochondria; ROS-dependent downregulated p-Akt, p-mTOR, and NF-κB (p65)	[85, 86]
Belinostat	Increase ROS-induced transforming growth factor-beta-activating kinase 1 (TAK1)/AMPK association to activate AMPK	[87]
TBMMP	Increase cytochrome c release, reduced mitochondrial membrane potential, activated caspase-3, caspase-9, elevated ROS, and increased expression of Bax	[88]
Isoalantolactone	Induce ROS-dependent apoptosis through intrinsic pathway	[89]
Gallic acid	Activated caspase-3, caspase-9, and reactive oxygen species	[90]
Dihydroartemisinin	DHA enhances Apo2L/TRAIL-mediated apoptosis in human pancreatic cancer cells through ROS-mediated upregulation of death receptor 5 (DR5)	[33]
BML-275	Induce ROS generation, DNA damage, and apoptosis via inhibition of the AMPK pathway and by inducing G2/M arrest via a pathway independent of AMPK	[91]
Nickel nanowires	Induce ROS-mediated apoptosis	[92]
Fenretinide	Induce apoptosis and autophagy and that sensitivity appears to be mediated by enhanced ROS	[93]
Sulforaphane	Induce autophagy depending on ROS	[94]
Brucein D	Activate redox-sensitive p38-MAPK pathway and inhibition of NF-κB antiapoptotic activity mediated by enhanced ROS	[1]
Artesunate	Induce ROS-mediated apoptosis	[95]
Nitric oxide-donating aspirin	ROS → MAPKs → p21 (cip-1) → cyclin D1 → cell death	[96]
Benzyl isothiocyanate	Activate ERK, JNK, and P38 at leading to the induction of apoptosis mediated by enhanced ROS	[97]
Arsenic trioxide and parthenolide	Induce reactive oxygen species generation and apoptosis via the mitochondrial pathway	[98]
Triphala	Phosphorylation of p53 and ERK induces apoptosis mediated by enhanced ROS	[99]
Capsaicin	Induce apoptosis through ROS generation and mitochondrial death pathway	[100]
Resveratrol	Damage mitochondrial function that leads to increased ROS, apoptosis	[101]