Journal
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
Volume 23, Issue 6, Pages 687-698Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1871520622666220826095035
Keywords
Thymelaea hirsuta; natural compounds; colorectal cancer cells; 5-Fluorouracil; apoptosis; cell cycle arrest
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This study evaluated the anti-tumoral activities of Thymelaea hirsuta L. extracts and their adjuvant potential in conventional colorectal cancer therapy. The ethyl acetate fraction induced cell cycle arrest and apoptosis, inhibited cell invasion, and potentiated colorectal cancer cells to 5-FU treatment.
Background: Conventional chemotherapeutic treatment of colorectal cancer has low efficiency because of its high toxicity. Several studies identified natural compounds as potential antitumor agents by inducing cancer cell cycle arrest or apoptosis and exhibiting a potential synergy in drug combination therapy. Natural compounds derived from plants represent an important source of pharmacologic agents toward several diseases. For example, the Tunisian Thymelaeaceae plants are used in folk medicine for the treatment of different pathologies such as diabetes and hypertension. Objective: The Thymelaea hirsuta L. extracts were evaluated for their anti-tumoral activities and their adjuvant potential that could be used in conventional colorectal cancer therapy. Methods: Fractionation of total methanolic extract from the plant leaves provided 4 fractions using vacuum liquid chromatography. The cytotoxic activities of these fractions were tested toward colorectal cancer cells. Results: Ethyl acetate fraction (E2 fraction) induced cell cycle arrest and apoptosis by activating caspase-3. E2 fraction inhibited cell invasion by reducing integrin alpha 5 expression and FAK phosphorylation. Moreover, E2 fraction potentialized colorectal cancer cells to 5-FU treatment. Conclusion: The selected plant Thymelaea hirsuta is the source of natural compounds that inhibited cell growth and invasion and induced cell cycle arrest in colorectal cancer cells. The most interesting result was their potential synergy in 5-FU combination treatment. Further analysis will identify the active compounds and confirm their role in chemotherapeutic treatment by sensitizing colorectal cancer cell to anti-cancer drugs.
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