Search

The biguanide metformin is a drug widely used for the treatment of type 2 diabetes. Metformin enhances the cytotoxicity of chemotherapy by promoting the adenosine monophosphate-activated protein kinase (AMPK) autophagy signaling pathway. Photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA), a precursor of protoporphyrin IX (PpIX), leads to apoptosis when PpIX accumulates in the mitochondria, and also leads to autophagy through activation of AMPK. In the present study, the effect of metformin in combination with 5-ALA-PDT was evaluated in vitro in KLN205 lung cancer cells. At a fluence of 5 J/cm2, 5-ALA-PDT in combination with 5 mM metformin exhibited significantly increased cytotoxicity compared with that observed with 0 and 0.1 mM metformin (P=0.0197 and P=0.0423, respectively). The cells treated with 5-ALA-PDT and metformin exhibited condensation of nuclear chromatin and the presence of autophagosomes. These results indicate that apoptosis and autophagy occur in KLN205 cells following combined treatment with 5-ALA-PDT and metformin. The results from the present study are the first to indicate, to the best of our knowledge, that metformin potentiates the efficacy of 5-ALA-PDT.

Melanoma is the most aggressive type of skin cancer and it is procured from activated or genetically altered epidermal melanocytes. In the present study, the tumor-suppressive effects of systemic and local injections of lupeol, a triterpene extracted from Indian lettuce (Lactuca indica), in a melanoma-bearing mouse model were evaluated. Mice were injected once with lupeol or olive oil (solvent control) subcutaneously into the skin of the back or into the tumor tissue. Seven days after the injection, the tumor growth rates were calculated and the tumor tissues were collected. Immunohistochemical staining for Ki-67 and proliferating cell nuclear antigen (PCNA) were performed. The tumor growth rates in the lupeol-injected group were significantly decreased compared to those observed in the non-treated (NT) and solvent control groups. Lupeol also significantly decreased the areas positively stained for Ki-67 and PCNA in the tumor tissues compared to those in the NT and solvent control groups. The results of the present study demonstrated that systemic and local injections of lupeol suppress tumor growth and induce cell cycle arrest in a melanoma-bearing mouse model. These data suggest that lupeol may be effective as a novel therapeutic option for melanoma patients.