ABSTRACT
Candelariella vitellina is common green-yellow lichen found on barks, wood, and rocks in Japanese forests. To investigate the mechanism of its anticancer potential, C. vitellina (80% MeOH/H2O) extract was prepared. High-performance liquid chromatography-high-resolution electrospray ionization mass spectrometry analysis revealed seven new compounds and 11 natural compounds of terpenes and polyketides. In vitro cytotoxicity analysis of Caco-2â¯cells exhibited an IC50 of 125⯱â¯4.1⯵g/mL. No significant cytotoxicity was observed in vitro in normal human peripheral lymphocytes. Both the IC25 and IC50 were determined to explore the potent anticancer potential in this study. C. vitellina exhibited a mitochondrial P53-independent apoptotic effect with negative P53 expression and an elevated BAX/BCL2 ratio as well as upregulated CASP3 mRNA expression. Similarly, in vivo analysis showed the same pattern of anticancer potential but was dependent on the P53 expression. Furthermore, C. vitellina induced antioxidative conditions in vitro and in vivo. The decreased invasion of tumor cells in vivo and increased apoptotic features in vitro and in vivo suggest the moderate to strong apoptotic anticancer potential of C. vitellina. However, further studies are needed to determine the extent and mechanism of action on different cell lines to support the anticancer properties of this lichen.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Lichens/chemistry , Plant Extracts/pharmacology , Animals , Antineoplastic Agents, Phytogenic/isolation & purification , Antioxidants/pharmacology , Apoptosis/genetics , Caco-2 Cells , Carcinoma, Ehrlich Tumor/pathology , Cell Survival/drug effects , Chromatography, Liquid , Female , Humans , In Vitro Techniques , Mice , Oxidative Stress , Polyketides/isolation & purification , Polyketides/pharmacology , RNA, Messenger/genetics , Spectrometry, Mass, Electrospray Ionization , Terpenes/isolation & purification , Terpenes/pharmacology , Xenograft Model Antitumor AssaysABSTRACT
Ganoderma applanatum is a widely distributed saprobic or parasitic mushroom, it was found at the bases of decaying logs in Hakozaki Higashi-ku Fukuoka-shi. Japan. The mushroom was extracted with 80% methanol, and LC-HRMS analysis was conducted to illustrate the bioactive ingredients. The cytotoxicity of the total metabolite extract was evaluated against human colon cancer cell line (Caco-2) which showed IC50 value of 160⯱â¯4.08⯵g/ml. G. applanatum methanolic extract caused different morphological alterations and increased glutathione level in the treated cells. Interestingly, G. applanatum increased Bax/Bcl-2 ratio significantly (Pâ¯Ëâ¯0.05) at concentrations of 80 and 160⯵g/ml on Caco-2 undergoing apoptotic p53-independent pathway with lake expression of p53 protein and up-regulated Cas-3 mRNA. The in vivo study on solid Ehrlich tumor (SEC) revealed a decrease in the volume of the developed tumor mass after five days of G. applanatum (200⯵g/ml) treatment. The apoptotic p53-dependant pathway was confirmed by mRNA Bax/Bcl-2 increased ratio in addition to p53 and Cas-3 up-regulation. In conclusion, G. applanatum could exert apoptotic antitumor properties in Caco-2 by p53-independent pathway and p53-dependant in SEC. The findings proved that G. applanatum can be a promising candidate as alternative or co-anticancer medications.