In vitro Anti-Metastatic Combination of the Naturally Occurring Chlorogenic Acid with Different Chemotherapies on Hepatocellular Carcinoma

Background: Cancer metastasis is deemed to be the principal cause of cancer death worldwide. Cancer therapy is actively evolving, but cancer-related mortality is still fearful. Although the currently-used cancer protocols could show anti-cancer efficiency; these protocols still lack specific anti-metastatic components. Aim: To test the efficiency of adding a naturally-occurring chlorogenic acid (CGA) to the three commonly used chemotherapeutics, 5-fluorouracil (5-FU) and doxorubicin (DOXO), and cisplatin (CIS) in preventing metastatic potential on HepG2 cell line. Methods: : After treating HepG2 with CGA alone or with 5-FU, DOXO, and CIS, the cellular lysate content of alpha-fetoprotein (AFP), metalloproteinases (MMP-3, MMP-9, and MMP-12), nitric oxide (NO), migration scratch assay and the gelatinolytic activity against a non-treated group were estimated. Results: : The treatment with CGA significantly reduced the levels of AFP and NO; along with the tested matrix metal­loproteinases, decreased gelatinolytic and migration activity in comparison to the non-treated HepG2 group (representative of hepatocellular carcinoma). CGA and CIS were more powerful than DOXO in the inhibition of cell migration (metastasis). However, the addition of CGA to CIS, DOXO, and 5-FU inhibited the cellular migration (metastasis) more than 5-FU alone. Conclusion: CGA showed a promising anti-metastatic activity when added to the studied chemotherapeutic drugs.