Luteolin as a glycolysis inhibitor offers superior efficacy and lesser toxicity of doxorubicin in breast cancer cells.
Luteolin (Lu) exhibits a wide spectrum of anti-tumor activities, the present study was to observe whether Lu can sensitize breast cancer cells to doxorubicin (Dox) and to explain the basis underlying this phenomenon. In vitro, Lu at dose less than 100 microM had only slight effect on cells growth and cytotoxicity of Dox in 4T1 and MCF-7 cells under normoxia, but it could reverse tumor resistance to Dox and promote death of tumor cells under hypoxia. In vivo, Lu alone had also no effect on tumor growth delay, however, it could offer superior efficacy and lesser toxicity of Dox in 4T1 and MCF-7 bearing mice. Further study showed that Lu was able to suppress glycolytic flux but did not affect glucose uptake, the P-glycoprotein, anti-oxidative enzymes under hypoxia in vitro, and had not also effect on the intratumor Dox level in vivo. In addition, the activity of SOD and CAT was increased in serum and was decreased in tumor by Lu in vivo. These results suggest that luteolin as a glycolytic inhibitor might be a new adjuvant agent for chemotherapy.
Du
Gang-Jun
GJ
Department of Pharmacology, Pharmaceutical College of Henan University, Jinming District, Kaifeng, Henan 475001, China.
Song
Zhi-Hui
ZH
Lin
Hai-Hong
HH
Han
Xiao-Feng
XF
Zhang
Shuo
S
Yang
Yi-Ming
YM
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D002374:Catalase / Q000097:blood; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology* / Q000633:toxicity; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D047311:Luteolin / Q000494:pharmacology*; D008315:Malondialdehyde / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013482:Superoxide Dismutase / Q000097:blood; D000072105:Superoxide Dismutase-1
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000277:Adjuvants, Pharmaceutic; D000970:Antineoplastic Agents; C000606290:SOD1 protein, human; D008315:Malondialdehyde; D004317:Doxorubicin; D002374:Catalase; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D005947:Glucose; D047311:Luteolin