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Published on: September 11, 2012
Effects of ursolic acid and oleanolic acid on human colon carcinoma cell line HCT15
Jie Li1, Wei-Jian Guo, Qing-Yao Yang
1Department of Oncology, Cancer Center, Xin Hua Hospital, Shanghai Second Medical University, Shanghai 200092, China. ljee@citiz.net
Aim:
Ursolic acid (UA) and oleanolic acid (OA) are triperpene acids having a similar chemical structure and are distributed wildly in plants all over the world. In recent years, it was found that they had marked anti-tumor effects. There is little literature currently available regarding their effects on colon carcinoma cells. The present study was designed to investigate their inhibitory effects on human colon carcinoma cell line HCT15.
Methods:
HCT15 cells were cultured with different drugs. The treated cells were stained with hematoxylin-eosin and their morphologic changes observed under a light microscope. The cytotoxicity of these drugs was evaluated by tetrazolium dye assay. Cell cycle analysis was performed by flow cytometry (FCM). Data were expressed as means +/-SEM and Analysis of variance and Student' t-test for individual comparisons.
Results:
Twenty-four to 72 h after UA or OA 60 micromol/L treatment, the numbers of dead cells and cell fragments were increased and most cells were dead at the 72nd hour. The cytotoxicity of UA was stronger than that of OA. Seventy-eight hours after 30 micromol/L of UA or OA treatment, a number of cells were degenerated, but cell fragments were rarely seen. The IC(50) values for UA and OA were 30 and 60 micromol/L, respectively. Proliferation assay showed that proliferation of UA and OA-treated cells was slightly increased at 24h and significantly decreased at 48 h and 60 h, whereas untreated control cells maintained an exponential growth curve. Cell cycle analysis by FCM showed HCT15 cells treated with UA 30 and OA 60 for 36 h and 72 h gradually accumulated in G(0)/G(1) phase (both drugs P<0.05 for 72 h), with a concomitant decrease of cell populations in S phase (both drugs P<0.01 for 72 h) and no detectable apoptotic fraction.
Conclusion:
UA and OA have significant anti-tumor activity. The effect of UA is stronger than that of OA. The possible mechanism of action is that both drugs have an inhibitory effect on tumor cell proliferation through cell-cycle arrest.
Insights
Ursolic acid (UA) and oleanolic acid (OA) show significant anti-tumor effects against colon cancer cells. UA demonstrates stronger cytotoxicity than OA, with both compounds inhibiting cell proliferation via cell-cycle arrest.
Area of Science:
- Pharmacology
- Oncology
- Natural Products Chemistry
Background:
- Ursolic acid (UA) and oleanolic acid (OA) are natural triterpenoids with known anti-tumor properties.
- Limited research exists on their specific effects on colon carcinoma cells.
- This study investigates the anti-cancer potential of UA and OA on the HCT15 human colon carcinoma cell line.
Purpose of the Study:
- To evaluate the inhibitory effects of UA and OA on HCT15 colon carcinoma cells.
- To compare the cytotoxicity and anti-proliferative activity of UA and OA.
- To elucidate the mechanism of action, focusing on cell cycle regulation.
Main Methods:
- HCT15 cells were treated with varying concentrations of UA and OA.
- Morphological changes were observed using light microscopy after hematoxylin-eosin staining.
- Cytotoxicity was assessed via tetrazolium dye assay, and cell cycle distribution was analyzed by flow cytometry (FCM).
Main Results:
- UA and OA treatments led to increased cell death and degeneration in a time- and dose-dependent manner.
- UA exhibited stronger cytotoxicity than OA, with IC50 values of 30 µmol/L for UA and 60 µmol/L for OA.
- Both compounds significantly decreased cell proliferation and induced G0/G1 phase cell cycle arrest in HCT15 cells.
Conclusions:
- UA and OA possess significant anti-tumor activity against human colon carcinoma cells.
- UA is more potent than OA in inhibiting HCT15 cell growth.
- The anti-cancer mechanism involves the inhibition of tumor cell proliferation through cell cycle arrest at the G0/G1 phase.
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