Licochalcone A inhibits the growth of colon carcinoma and attenuates cisplatin-induced toxicity without a loss of chemotherapeutic efficacy in mice.

Abstract

Although chemotherapy has an important function in the treatment of most solid tumours, its clinical applications are limited by severe side effects such as nephrotoxicity, hepatotoxicity, ototoxicity and neurotoxicity. Recently, a growing amount of attention has been focused on the investigation of the effects of chemopreventive agents on the inhibition of cancer cell growth and toxicity in combination with chemotherapeutics. The aim of this study was to determine whether licochalcone A (LCA) has the potential to serve as a beneficial supplement during cisplatin chemotherapy. We found that the administration of LCA alone significantly inhibited the size of the solid tumours in CT-26 cell-inoculated Balb/c mice, without any detectable induction of nephrotoxicity, hepatotoxicity and oxidative stress. LCA also suppressed cell proliferation by reducing DNA synthesis of CT-26 murine colon cancer cells in a dose-dependent manner. LCA did not affect the therapeutic efficacy of cisplatin. Furthermore, LCA inhibited the cisplatin-induced kidney damage characterized by increases in the serum creatinine and blood urea nitrogen, as well as the cisplatin-induced liver damage characterized by increases in the serum alanine aminotransferase and aspartate aminotransferase. The repeated oral administration of LCA prior to cisplatin treatment exerted a preventive effect on the cisplatin-mediated increases in the serum nitric oxide and the tissue lipid peroxidation levels, and recovered the depleted reduced glutathione levels in the tissues. These results suggest that supplementation with LCA may be beneficial in counteracting the side effects of cisplatin therapy in cancer patients.

• Authors: Chang Ki Lee, Seung Hwa Son, Kwang Kyun Park, Jung Han Yoon Park, Soon Sung Lim, Sook-Hyang Kim, Won Yoon Chung
• Journal: Basic & clinical pharmacology & toxicology (Basic Clin Pharmacol Toxicol) Vol. 103 Issue 1 Pg. 48-54 (Jul 2008) ISSN: 1742-7843 [Electronic] England
• PMID: 18484961 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticarcinogenic Agents
• Antineoplastic Agents
• Antioxidants
• Chalcones
• Nitric Oxide
• Creatinine
• Aspartate Aminotransferases
• Alanine Transaminase
• Glutathione
• licochalcone A
• Cisplatin

Topics

• Administration, Oral
• Alanine Transaminase (blood)
• Animals
• Anticarcinogenic Agents (therapeutic use)
• Antineoplastic Agents (adverse effects, therapeutic use)
• Antioxidants (therapeutic use)
• Aspartate Aminotransferases (blood)
• Blood Urea Nitrogen
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Chalcones (therapeutic use)
• Cisplatin (adverse effects, therapeutic use)
• Colonic Neoplasms
• Creatinine (blood)
• Drug Therapy, Combination
• Glutathione (metabolism)
• In Vitro Techniques
• Kidney (drug effects, metabolism, pathology)
• Lipid Peroxidation (drug effects)
• Liver (drug effects, metabolism, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Neoplasm Transplantation
• Nitric Oxide (blood)
• Oxidative Stress (drug effects)
• Transplantation, Heterologous