Extracts from Citrus unshiu promote immune-mediated inhibition of tumor growth in a murine renal cell carcinoma model.
OBJECTIVE
Citrus unshiu (Satsuma mandarin, SM) is a citrus fruit the peel of which has been used as a traditional Chinese medicine to treat common cold, relieve exhaustion, and cancer. In this study, we examined how effectively the content and peel extracts of SM can suppress cancer growth. The mechanism underlying cancer-suppressing properties of SM was investigated in tumor-bearing mice with renal carcinoma cell, Renca.


METHODS
Effectiveness of SM in tumor suppression was evaluated by measuring size of tumor mass in tumor-bearing mice treated with various doses of SM content and peel extracts. Proliferation of tumor cells and splenocytes was determined by MTT assay and [³H]TdR uptake, respectively. Relevant immunological mechanisms were chased by assaying cytokines including TGF-β, IL-6, IFN-γ, and TNF-α by ELISA.


RESULTS
The content and peel extracts of SM inhibited the growth of tumor cells in tumor-bearing mice. Especially, average tumor volume of two groups treated with 3 and 30 mg peel extracts per mouse weight (kg) were significantly decreased to 52.32% (p<0.05) and 68.72% (p<0.01), respectively. To identify tumor regression mechanism, anti-tumor cytokines measured in Con A-activated splenocytes from tumor-bearing mice. IFN-γ was increased in both of the peel extract-treated groups, while TNF-α, which had been decreased by tumor growth, was rescued to the normal level in SM content and peel extracts-treated groups. However, SM content and peel extracts did not inhibit proliferation and tumor-proliferative cytokines including TGF-β and IL-6 production of tumor cells.


CONCLUSIONS
These results indicate that SM content and peel extracts have anti-tumor properties in the tumor-bearing murine model. The mechanism underlying the anti-tumor effects of SM extracts is strongly suggested to be via boosting cytokines such as IFN-γ and TNF-α, enhancing immune-mediated anti-tumor properties.
Lee
Sanggon
S
Department of Microbiology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
Ra
Jehyeon
J
Song
Ju-Young
JY
Gwak
ChangHo
C
Kwon
Ha-Jeong
HJ
Yim
Sung-Vin
SV
Hong
Seon-Pyo
SP
Kim
Jinju
J
Lee
Kun-Hee
KH
Cho
Jeong-Je
JJ
Park
Yong Seek
YS
Park
Cheung-Seog
CS
Ahn
Hyun-Jong
HJ
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects* / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D002957:Citrus / Q000737:chemistry*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005419:Flavonoids / Q000032:analysis; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects
D016207:Cytokines; D005419:Flavonoids; D010936:Plant Extracts