ROS-Mediated Therapeutic Strategy in Chemo-/Radiotherapy of Head and Neck Cancer

Table 3

Small molecular compounds modulating ROS in chemo-/radiotherapy of HNC.

Compound	Site	Experimental model	Effective dose	Cotherapy	ROS detection	Biological effect	Mechanisms	Reference
CHW09	Oral cavity	In vitro; (Ca9-22, CAL 27 cancer cell, and normal gingival fibroblast HGF-1 cell)	10 μg/ml	+Radiation; (12 Gy)	DCFH-DA flow cytometry	Synergistic effects	↑ROS, ↑CC3, ↑CC8, ↑c-PARP, ↑8-oxodG, ↑γH2AX	[195]
Oxamate	Nasopharynx	In vitro; (CNE-1, CNE-2 cell); In vivo; (CNE-1 xenograft nude mice)	In vitro; (20, 50, 100 mM); In vivo; (750 mg/kg daily for 3 weeks)	+Radiation; (9.9 Gy)	DCFH-DA flow cytometry	Synergistic effect: enhances apoptosis and G2/M arrest	↑ROS, ↓ATP, ↓CDK1/cyclin B1, ↓Bcl-2, ↑Bax, ↑CC3	[197]
D-Allose	Tongue	In vitro; (HSC-3 cell)	25 mM	+Radiation; (4 Gy)	DCFH-DA fluorescence microscopy	Synergistic effect: enhances apoptosis	↑ROS, ↑TXNIP, ↓TRX	[201]
D-Allose	Tongue	In vitro; (HSC-3 cell); In vivo; (HSC-3 xenograft nude mice)	In vitro; (10 mM); In vivo; (500 mM 5 times/week for 3 weeks)	+Docetaxel; In vitro; (0.1 ng/ml); In vivo; (12 mg/kg on day 0 and day 7)	DCFH-DA fluorescence microscopy	Synergistic effect: enhances apoptosis G2/M arrest	↑ROS, ↑TXNIP, ↓TRX	[202]
SAHA	Nasopharynx	In vitro; (HK1-EBV, HONE1-EBV, HA, C666-1, NP460, HK2 cell); In vivo; (C666-1, HONE1, HA xenograft nude mice)	In vitro; (5 μM); In vivo; (50 mg/kg 5 days per week for 4 weeks)	+Bortezomib; In vitro; (30 nM); In vivo; (60 μg/kg)	DCFH-DA flow cytometry	Synergistic effect: enhances apoptosis	↑ROS, ↑c-PARP, ↑CC3, ↑CC7, ↑CC9	[146]
NaB	Esophagus	In vitro; (KYSE-150, KYSE-150R cells)	0.5, 1 μM	+Radiation (5 Gy)	DCFH-DA flow cytometry	Synergistic effect: enhances apoptosis, G2/M arrest, and DNA damage	↑ROS, ↓Bmi-1, ↑p21, ↓DNA-PKcs, ↓NBS1, ↓Rad51, ↑γH2AX	[65]
TSA	Esophagus	In vitro; (KYSE-150, KYSE-150R cells)	5, 10 mM	+Radiation (5 Gy)	DCFH-DA flow cytometry	Synergistic effect enhances apoptosis, G2/M arrest, and DNA damage	↑ROS, ↓Bmi-1, ↑p21, ↓DNA-PKcs, ↓NBS1, ↓Rad51, ↑γH2AX	[65]

Note. ROS: reactive oxygen species; DCFH-DA: 2,7-dichlorofluorescein diacetate; CHW09: sulfonyl chromen-4-ones; SAHA: vorinostat; NaB: sodium butyrate; TSA: hydroxamic acid trichostatin A; c-PARP: poly-ADP ribose polymerase; CC3: cleaved caspase 3; CC7: cleaved caspase 7; CC8: cleaved caspase 8; CC9: cleaved caspase 9; 8-oxodG: 8-oxo-2-deoxyguanosine; γH2AX: H2A histone family member X; NQO1: NAD(P)H:quinone oxidoreductase 1; Bcl-2: B-cell lymphoma-2; Bax: Bcl-2-associated X protein; ATP: adenosine-triphosphate; CDK1: cyclin-dependent kinase 1; c-PARP: cleaved PARP; Bmi-1: B-lymphoma Mo-MLV insertion region 1; p21: protein 21; DNA-PKcs: DNA-dependent protein kinase, catalytic unit; NBS1: Nijmegen breakage syndrome 1; RAD51: radioresistance protein 51; TXNIP: Trx-interacting protein.