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In vitro anti-proliferative activities of ellagic acid
Jack N Losso1, Rishipal R Bansode, Alfred Trappey
1Department of Food Science, Louisiana State University, Agricultural Center, Baton Rouge, LA 70803, USA. jlosso@lsu.edu
Abstract:
The potential cytotoxic and anti-proliferative activities of ellagic acid (a naturally occurring bioactive compound in berries, grapes, and nuts) was evaluated using human umbilical vein endothelial cells (HUVEC), normal human lung fibroblast cells HEL 299, Caco-2 colon, MCF-7 breast, Hs 578T breast, and DU 145 human prostatic cancer cells. Ellagic acid at concentration in the range 10-100 micromol/L did not affect the viability of normal fibroblast cells during a 24-hour incubation. An increase in adenosine triphosphate (ATP) bioluminescence of approximately 18-21% was observed in normal cells incubated with ellagic acid. In contrast, ellagic acid at 1-100 micromol/L dose-dependently inhibited HUVEC tube formation and proliferation on a reconstituted extracellular matrix and showed strong anti-proliferative activity against the colon, breast, and prostatic cancer cell lines investigated. The most sensitive cells were the Caco-2, and the most resistant were the breast cancer cells. Ellagic acid induced cancer cell death by apoptosis as shown by the microscopic examination of cell gross morphology. Ellagic acid induced reduced cancer cell viability as shown by decreased ATP levels of the cancer cells. After 24 hours incubation of 100 micromol/L of ellagic acid with Caco-2, MCF-7, Hs 578T, and DU 145 cancer cells, ellagic acid suppressed fetal bovine serum (FBS) stimulation of cell migration. The apoptosis induction was accompanied by a decreased in the levels of pro-matrix metalloproteinase-2 (pro-MMP-2 or gelatinase A), pro-matrix metalloproteinase-9 (pro-MMP-9 or gelatinase B), and vascular endothelial growth factor (VEGF(165)) in conditioned media. The results suggest that ellagic acid expressed a selective cytotoxicity and anti-proliferative activity, and induced apoptosis in Caco-2, MCF-7, Hs 578T, and DU 145 cancer cells without any toxic effect on the viability of normal human lung fibroblast cells. It was also observed that the mechanism of apoptosis induction in ellagic acid-treated cancer cells was associated with decreased ATP production, which is crucial for the viability of cancer cells.
Insights
Ellagic acid selectively targets cancer cells, inducing apoptosis and inhibiting proliferation without harming normal cells. This natural compound reduces cancer cell viability by decreasing adenosine triphosphate (ATP) production.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Ellagic acid is a natural polyphenol found in fruits and nuts.
- Cancer cells exhibit distinct metabolic vulnerabilities compared to normal cells.
- Targeting cancer cell proliferation and survival pathways is a key therapeutic strategy.
Purpose of the Study:
- To evaluate the cytotoxic and anti-proliferative effects of ellagic acid on various human cancer cell lines.
- To investigate the impact of ellagic acid on normal human lung fibroblast cells.
- To elucidate the mechanisms underlying ellagic acid's anti-cancer activity, including apoptosis induction and metabolic effects.
Main Methods:
- Cell viability assays (adenosine triphosphate bioluminescence) were performed on normal and cancer cell lines.
- In vitro assays assessed HUVEC tube formation and proliferation.
- Cancer cell apoptosis, morphology, ATP levels, migration, and specific protein expressions (MMPs, VEGF) were analyzed.
Main Results:
- Ellagic acid demonstrated selective cytotoxicity against colon, breast, and prostate cancer cells (Caco-2, MCF-7, Hs 578T, DU 145) at 1-100 micromol/L.
- Normal fibroblast cells showed no significant decrease in viability; ATP levels even increased.
- Ellagic acid inhibited cancer cell proliferation, induced apoptosis, reduced ATP levels, suppressed migration, and decreased pro-MMP-2, pro-MMP-9, and VEGF(165) levels.
Conclusions:
- Ellagic acid exhibits selective anti-cancer properties, inducing apoptosis and inhibiting proliferation in various cancer types.
- The anti-cancer mechanism involves decreased ATP production, crucial for cancer cell viability.
- Ellagic acid presents a promising natural compound for cancer therapy with minimal toxicity to normal cells.
