Total flavonoids of Daphne genkwa root significantly inhibit the growth and metastasis of Lewis lung carcinoma in C57BL6 mice.
Daphne genkwa root has been traditionally used as an effective remedy to treat various tumors. However, the active constituents for its antitumor potency have not been well documented. During the screening for antitumor constituents, it was found that the total flavonoids of D. genkwa root (TFDR) were responsible for the inhibition of tumor growth and metastasis. In this study, TFDR was investigated for its chemical composition and activities against tumor growth and metastasis. HPLC indicates that daphnodorin B, containing 42.79% of the total, represents the predominant constituent in TFDR. Treatment of LLC-bearing mice with TFDR evidently protected peripheral lymphocytes from tumor-induced reduction, and increased lymphocyte proliferation potential and cytolytic activity of NK, and inhibited tumor progression and metastasis either 7 days before, or simultaneous with, or 7 days after LLC transplantation. TFDR also suggested higher cytotoxicity to a number of tumor cell lines than that to normal human kidney cell K293. TFDR also induced an enhancement on peripheral release of TNF-alpha at doses between 25 and 75 mg/kg. These results indicated that TFDR inhibited tumor growth and metastasis by protecting host immunocyte viability and its proliferation potential, and selectively inhibiting tumor cell proliferation, and improving cytolytic activity of NK cells, and enhancing TNF release in LLC-bearing mice. Daphnodorin B and its analogues in TFDR are the active constituents in the roots of D. genkwa, contributing to the inhibition of tumor growth and metastasis.
Zheng
Weifa
W
Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, Xuzhou Normal University, Xuzhou, China. yyzw@xznu.edu.cn
Gao
Xiaowen
X
Chen
Caifa
C
Tan
Renxiang
R
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D032364:Daphne / Q000737:chemistry*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D013154:Spleen / Q000187:drug effects / Q000254:growth & development / Q000276:immunology; D013950:Thymus Gland / Q000187:drug effects / Q000254:growth & development / Q000276:immunology; D047368:Tumor Burden / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha