title: 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.affiliation: Department of Oral Biology, Oral Cancer Research Institute, Oral Science Research Institute, Brain Korea 21 Project, Yonsei University College of Dentistry, Yonsei University, Seoul, South Korea.
authors.forename: Chang Ki
authors.initials: CK
authors.lastname: Lee
authors.forename: Seung Hwa
authors.initials: SH
authors.lastname: Son
authors.forename: Kwang Kyun
authors.initials: KK
authors.lastname: Park
authors.forename: Jung Han Yoon
authors.initials: JH
authors.lastname: Park
authors.forename: Soon Sung
authors.initials: SS
authors.lastname: Lim
authors.forename: Sook-Hyang
authors.initials: SH
authors.lastname: Kim
authors.forename: Won Yoon
authors.initials: WY
authors.lastname: Chung
mesh_terms: D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D001806:Blood Urea Nitrogen; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000627:therapeutic use*; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D003110:Colonic Neoplasms; D003404:Creatinine / Q000097:blood; D004359:Drug Therapy, Combination; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D014183:Transplantation, Heterologous
chemical_list: D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D000975:Antioxidants; D047188:Chalcones; D009569:Nitric Oxide; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; C070840:licochalcone A; D002945:Cisplatin