Screening of biochemical modulator by tumor cell permeability of doxorubicin.
We screened various food components for their ability to inhibit doxorubicin (DOX) permeability in tumor cells in vitro with the aim of finding novel modulators. Capsaicin did not change DOX permeability in the tumor cells, although the capsaicin derivatives gingerol and ferulic acid tended to promote DOX efflux. Combinations of these components with DOX were also not effective. In contrast, cucurbitacin E significantly promoted DOX influx into tumor cells and increased DOX concentration in tumor cells. Furthermore, combined cucurbitacin E significantly suppressed DOX efflux from tumor cells and was shown to maintain the DOX level in tumor cells. It was also confirmed that the combination of cucurbitacin E with DOX resulted in effective cytotoxicity for tumor cells in culture. Additionally, the combination of cucurbitacin E and DOX showed increased cytotoxicity when compared to each treatment alone. In vivo, DOX alone treatment did not change the time course of tumor size or tumor weight of M5076 ovarian sarcoma, compared to control levels. In contrast, the combination of cucurbitacin E with DOX resulted in decreased tumor size and tumor weight, compared to that in DOX alone group, indicating effective antitumor activity. In conclusion, the combination of cucurbitacin E with DOX may be an effective tool with treated application in the cancer chemotherapy.
Laboratory of Pharmaceutical Engineering, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. sadzuka@u-shizuoka-ken.ac.jp
Yasuyuki
Y
Sadzuka
Haruna
H
Hatakeyama
Takashi
T
Daimon
Takashi
T
Sonobe
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics* / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy*; D002396:Catechols; D045744:Cell Line, Tumor; D003373:Coumaric Acids / Q000494:pharmacology; D004317:Doxorubicin / Q000493:pharmacokinetics* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005233:Fatty Alcohols / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010539:Permeability / Q000187:drug effects; D012509:Sarcoma / Q000188:drug therapy; D014315:Triterpenes / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D002396:Catechols; D003373:Coumaric Acids; D005233:Fatty Alcohols; D014315:Triterpenes; D004317:Doxorubicin; C007845:gingerol; C004999:ferulic acid; D002211:Capsaicin; C102326:cucurbitacin E