Synergistic antitumor efficacy of antibacterial helvolic acid from Cordyceps taii and cyclophosphamide in a tumor mouse model.
The antibacterial agent helvolic acid, which was isolated from the active antitumor fraction of Cordyceps taii, showed potent cytotoxicity against different human cancer cells. In the present study, the in vivo antitumor effect of helvolic acid was investigated in murine sarcoma S180 tumor-bearing mice. Doses of 10 and 20 mg/kg/day helvolic acid did not exert significant antitumor activity. Interestingly, co-administration of 10 mg/kg/day helvolic acid and 20 mg/kg/day cyclophosphamide (CTX) - a well-known chemotherapy drug - showed promising antitumor activity with a growth inhibitory rate of 70.90%, which was much higher than that of CTX alone (19.5%). Furthermore, the combination markedly prolonged the survival of tumor-bearing mice. In addition, helvolic acid enhanced the immune organ index. The protein expression levels of β-catenin, cyclin D1, and proliferating cell nuclear antigen were significantly suppressed in mice treated with 20 mg/kg/day helvolic acid and in those receiving combination therapy. Taken together, these results indicated that helvolic acid in combination with CTX showed potent in vivo synergistic antitumor efficacy, and its mechanism of action may involve the Wnt/ β-catenin signaling pathway.
1 Centre for Translational Medicinal of Guizhou Province, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, PR China.
Jian-Hui
JH
Xiao
1 Centre for Translational Medicinal of Guizhou Province, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, PR China.
Yao
Y
Zhang
1 Centre for Translational Medicinal of Guizhou Province, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, PR China.
Gui-You
GY
Liang
1 Centre for Translational Medicinal of Guizhou Province, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, PR China.
Ru-Ming
RM
Liu
1 Centre for Translational Medicinal of Guizhou Province, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, PR China.
Xiao-Gang
XG
Li
1 Centre for Translational Medicinal of Guizhou Province, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, PR China.
Ling-Tao
LT
Zhang
1 Centre for Translational Medicinal of Guizhou Province, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, PR China.
Dai-Xiong
DX
Chen
2 State Key Laboratory of Microbial Metabolism, and School of Life Science & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, PR China.
Jian-Jiang
JJ
Zhong
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D045744:Cell Line, Tumor; D032661:Cordyceps / Q000737:chemistry; D019938:Cyclin D1 / Q000378:metabolism; D003520:Cyclophosphamide / Q000494:pharmacology*; D004195:Disease Models, Animal; D004357:Drug Synergism; D005672:Fusidic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051379:Mice; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012509:Sarcoma / Q000188:drug therapy*; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism
D000970:Antineoplastic Agents; C530105:Ccnd1 protein, mouse; D018809:Proliferating Cell Nuclear Antigen; D051153:Wnt Proteins; D051176:beta Catenin; D019938:Cyclin D1; D005672:Fusidic Acid; D003520:Cyclophosphamide; C011267:helvolic acid
Cordyceps taii; Medicinal mushroom; antitumor activity; cyclophosphamide; helvolic acid; mechanism of action; synergistic effect