Notoginseng enhances anti-cancer effect of 5-fluorouracil on human colorectal cancer cells.
OBJECTIVE
Panax notoginseng is a commonly used Chinese herb. Although a few studies have found that notoginseng shows anti-tumor effects, the effect of this herb on colorectal cancer cells has not been investigated. 5-Fluorouracil (5-FU) is a chemotherapeutic agent for the treatment of colorectal cancer that interferes with the growth of cancer cells. However, this compound has serious side effects at high doses. In this study, using HCT-116 human colorectal cancer cell line, we investigated the possible synergistic anti-cancer effects between notoginseng flower extract (NGF) and 5-FU on colon cancer cells.


METHODS
The anti-proliferation activity of these modes of treatment was evaluated by MTS cell proliferation assay. Apoptotic effects were analyzed by using Hoechst 33258 staining and Annexin-V/PI staining assays. The anti-proliferation effects of four major single compounds from NGF, ginsenosides Rb1, Rb3, Rc and Rg3 were also analyzed.


RESULTS
Both 5-FU and NGF inhibited proliferation of HCT-116 cells. With increasing doses of 5-FU, the anti-proliferation effect was slowly increased. The combined usage of 5-FU 5 microM and NGF 0.25 mg/ml, significantly increased the anti-proliferation effect (59.4 +/- 3.3%) compared with using the two medicines separately (5-FU 5 microM, 31.1 +/- 0.4%; NGF 0.25 mg/ml, 25.3 +/- 3.6%). Apoptotic analysis showed that at this concentration, 5-FU did not exert an apoptotic effect, while apoptotic cells induced by NGF were observed, suggesting that the anti-proliferation target(s) of NGF may be different from that of 5-FU, which is known to inhibit thymidilate synthase.


CONCLUSIONS
This study demonstrates that NGF can enhance the anti-proliferation effect of 5-FU on HCT-116 human colorectal cancer cells and may decrease the dosage of 5-FU needed for colorectal cancer treatment.
Wang
Chong-Zhi
CZ
Tang Center for Herbal Medicine Research, The University of Chicago, Chicago, IL 60637, USA.
Luo
Xiaoji
X
Zhang
Bin
B
Song
Wen-Xin
WX
Ni
Ming
M
Mehendale
Sangeeta
S
Xie
Jing-Tian
JT
Aung
Han H
HH
He
Tong-Chuan
TC
Yuan
Chun-Su
CS
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D035264:Flowers / Q000737:chemistry; D005472:Fluorouracil / Q000494:pharmacology*; D036145:Ginsenosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D015394:Molecular Structure; D053723:Panax notoginseng / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D051381:Rats
D000964:Antimetabolites, Antineoplastic; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D010936:Plant Extracts; D005472:Fluorouracil