Table 2.

Chemopotentiating activities of ATO against various neoplastic diseases.

ATO in Combination with Chemo Agents	Experimental Models	Identified Molecular Targets and Signaling Pathways	Outcome of Combinatorial Treatment	References
Dasatinib	In vitro	Activated the UPR apoptotic IRE1/JNK/PUMA axis, neutralized the UPR ATF4-dependent anti-apoptotic axis	Increased apoptosis in both TKI-sensitive and resistant Ph+ ALL cell lines	[97]
Erlotinib	In vitro	Triggered ATO-induced apoptosis in GBM cell lines and increased reactive oxygen species generation	Synergistically reduced metabolic activity, proliferation and colony forming potential in treated GBM cell lines	[94]
All-trans retinoic acid (ATRA)	In vitro and In vivo	↑ Apoptosis of NB4 cells and ↓ serum IL-6 and TNF-α levels in patients with APL	Significantly inhibits the proliferation of NB4 cells and promotes their apoptosis, and reduces inflammatory responses in patients with APL	[98]
Cisplatin	In vitro	Induced apoptotic cell death	Displayed significant anti-cancer activity in a panel of human cancer cell lines and overcame the tumor-based drug resistance	[99]
Temozolomide (TMZ) and Vismodegib (VIS)	In vitro and In vivo	Damaged the DNA repair enzyme encoded in the human as O6-methylguanine-DNA methyltransferase (MGMT) and inhibited The Hedgehog (Hh) signalling pathway	Synergistically inhibited the proliferation of glioblastoma and decreased tumor growth in mice	[100]
Silibin	In vitro	Decreased the mRNA levels of cathepsin B, urokinase-type plasminogen activator, Bcl-2 and upregulated caspase-3	Synergistically inhibits glioma cell proliferation and induced apoptosis	[101]
Paclitaxel	In vitro and In vivo	Inhibited the expression of Bcl-2, caspase-7, caspase-9, cyclin B-1, and cyclin D-1; induced apoptosis	Significantly affected cell-cycle and induced apoptosis	[102]
Vincristine	In vitro	Triggered caspase-dependent apoptosis via the mitochondrial pathway	Synergistically induced apoptosis	[103]
Butylthionine sulfoxide	In vitro	Depleted intracellular GSH	Enhanced the ATO-toxicity in C6 cells	[104]
Ascorbic acid	In vitro	Activated caspase-3 to trigger apoptosis, upregulated the expression of caspase-1 and promoted formation of inflammasomes	Enhanced the proapoptotic effects of arsenic, synergistically inhibited the viability of human CRC cells	[26]
Itraconazole	In vivo	Modulating Hedgehog (Hh) pathway	Effectively reduced tumor growth of medulloblastoma cells	[23]
Sulindac	In vitro	Increased the catalytic activity of caspase-3, -8, and -9 along with induction of Fas/FasL expression and cytosolic release of cytochrome c	Synergistically enhanced cytotoxicity to NCI-H157 lung cancer cells	[105]
Indomethacin	In vitro	Activation of ERK and p38 pathways, considerably high Caspase-3 activity	Exerted a very potent in vitro cytotoxic effect against A549 lung cancer cells	[106]
SiRNA-directed Kras oncogene silencing	In vitro and In vivo	Down-regulation of the mutant Kras gene by siRNA and tumor growth inhibition of arsenic	Inhibited proliferative, migratory and invasive pancreatic cancer cells, and substantially improved the apoptotic effect	[107]
Blue LED irradiation	In vitro	Increased ROS accumulation, DNA damaged mediated p53 activation	Significantly decreased the percentages of proliferative cells, and increased apoptotic rate on human osteosarcoma	[108]