[Salvianolic acid A inhibits nucleoside transport and potentiates the antitumor activity of chemotherapeutic drugs].
OBJECTIVE
To investigate the inhibitory activity of salvianolic acid A (SAA) on nucleoside transport in cancer cells and its antitumor effect.


METHODS
[3H] thymidine and [3H] uridine transport assays were used to determine the inhibitory activity on nucleoside transport in Ehrlich carcinoma cells. The cytotoxicity to cultured cancer cells was examined with clonogenic assay. The antitumor effect in vivo was evaluated with transplantable tumor model in mice.


RESULTS
SAA was shown to inhibit thymidine and uridine transport in Ehrlich carcinoma cells with IC50 values of 18.1 and 17.1 micromol x L(-1), respectively. By clonogenic assay, the IC50 of SAA for KB cells was 44.7 micromol x L(-1). SAA markedly potentiated the cytotoxicity of 5-FU and mitomycin C in KB cells as well as the cytotoxicity of MTX in human hepatoma BEL-7402 cells. For in vivo experiment, sarcoma 180 cells were transplanted sc in mice and tested drugs were administered ip. When administered separately, SAA at 200 mg x kg(-1) and 5-FU at 10 mg x kg(-1) inhibited tumor growth by 41% and 27%, respectively. Combination of the two drugs inhibited tumor growth by 63% (CDI = 0.86).


CONCLUSIONS
SAA is active in blocking nucleoside transport in cancer cells and potentiates the cytotoxicity of chemotherapeutic drugs. As an agent showing moderate antitumor effect in vivo, SAA might be useful in combination cancer therapy.
Zhang
Sheng-Hua
SH
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Su
Jian
J
Zhen
Yong-Su
YS
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D001692:Biological Transport; D002109:Caffeic Acids / Q000302:isolation & purification / Q000494:pharmacology*; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D007624:KB Cells; D007773:Lactates / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D008727:Methotrexate / Q000494:pharmacology; D051379:Mice; D016685:Mitomycin / Q000494:pharmacology; D009368:Neoplasm Transplantation; D010946:Plants, Medicinal / Q000737:chemistry; D027561:Salvia miltiorrhiza / Q000737:chemistry; D012510:Sarcoma 180 / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D002109:Caffeic Acids; D004365:Drugs, Chinese Herbal; D007773:Lactates; D016685:Mitomycin; C066201:salvianolic acid A; D005472:Fluorouracil; D008727:Methotrexate