Curcumin reduced the side effects of mitomycin C by inhibiting GRP58-mediated DNA cross-linking in MCF-7 breast cancer xenografts.
Mitomycin C (MMC), a chemotherapeutic agent in breast cancer treatments, inhibits tumor growth through DNA cross-linking and breaking, but it has severe side effects. Here we examined whether and how curcumin reduced the side effects of MMC. We found that combination treatment with MMC and curcumin reduced tumor weight by 70% and 36% compared with saline and curcumin-treated groups, respectively. The combination treatment reduced weight loss and improved kidney function and bone marrow suppression compared with MMC treatment alone. Moreover, the combination treatment inhibited glucose regulatory protein (GRP58)-mediated DNA cross-linking. The combination treatment inhibited GRP58 through the ERK/p38 MAPK pathway. In conclusion, the current study provided evidence that MMC and curcumin combination treatment reduced MMC side effects by inhibiting GRP58-mediated DNA cross-linking through the ERK/p38 MAPK pathway.
Zhou
Qian-Mei
QM
Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Zhang
Hui
H
Lu
Yi-Yu
YY
Wang
Xiu-Feng
XF
Su
Shi-Bing
SB
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents / Q000009:adverse effects*; D003474:Curcumin / Q000627:therapeutic use*; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D016685:Mitomycin / Q000009:adverse effects*; D009368:Neoplasm Transplantation; D019704:Protein Disulfide-Isomerases / Q000037:antagonists & inhibitors*; D014183:Transplantation, Heterologous; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
D000903:Antibiotics, Antineoplastic; D003432:Cross-Linking Reagents; D016685:Mitomycin; D004247:DNA; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C513195:Pdia3 protein, mouse; D019704:Protein Disulfide-Isomerases; D003474:Curcumin
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