The Tumorigenic Roles of the Cellular REDOX Regulatory Systems

Table 1

Chemotherapeutic drugs commonly used in the clinic capable of inducing ROS.

Drug name	Tumor type	Mechanism of action for ROS induction	References
Actinomycin D	Sarcomas; Wilms’ tumor; testicular; melanoma; neuroblastoma; germ cell; retinoblastoma; choriocarcinoma	Inhibition of Bcl-2	[179]
Bleomycin	Melanoma; Hodgkin’s and non-Hodgkin’s lymphomas; testicular; head and neck; cervical; malignant pleural effusions	Formation of Fe(II)-bleomycin-DNA complex that is oxidized by O2	[185, 187]
Busulfan	Chronic myeloid leukemia	GSH depletion and NOX activation	[182, 183]
Carmustine	Brain; Hodgkin’s and non-Hodgkin’s lymphoma; melanoma; myeloma	GSH depletion via inhibition of GR	[169]
Cisplatin	Ovarian; colon; testicular; germ cell; bladder; lung; head and neck	Increased expression of p47 subunit of NOX	[17, 188]
DMAT	Prostate	Inhibition of CK2 activity	[173]
Doxorubicin	Hodgkin’s and non-Hodgkin’s lymphoma; leukemia; breast; gastric; neuroblastoma; ovarian; lung; soft tissue and bone sarcomas; thyroid; bladder	p53-dependent transcription of cytochrome oxidase 2; FOXO3-dependent transcription of Noxa and BIM; quinone metabolism	[190]
Etoposide	Lymphomas; leukemias; neuroblastoma; breast; lung; testicular; gastric	FOXO3 dependent transcription of Noxa and BIM	[188, 190]
5-Fluorouracil	Gastric; colon; gynecological; breast; head and neck; lung; skin	p53-dependent transcription of ROMO 1	[188, 189]
Gemcitabine	Pancreatic; lung; in combination with other drugs: breast, bladder, and ovarian	Activation of AKT and ERK 1/2 which leads to upregulation of CXCR4	[198]
Mitomycin C	Colon; breast; head and neck; bladder; cervical; gastric; pancreatic; liver	Inhibition of Bcl-2	[180, 202]
Paclitaxel	Ovarian; breast; non-small cell lung carcinoma; Kaposi’s sarcoma	Activation of Rac1 subunit of NOX; disruption of the mitochondrial membrane	[177, 178]
Tamoxifen	Breast	Inhibition of CK2 activity	[175]