Ganoderma applanatum secondary metabolites induced apoptosis through different pathways: In vivo and in vitro anticancer studies

• Published in: Biomedicine & pharmacotherapy Vol. 101; pp. 264 - 277
• Main Authors: Elkhateeb, Waill A., Zaghlol, Gihan M., El-Garawani, Islam M., Ahmed, Eman F., Rateb, Mostafa E., Abdel Moneim, Ahmed E.
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.05.2018
• Subjects: Animals; Anticancer; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Caco-2; Caco-2 Cells; Carcinoma, Ehrlich Tumor - drug therapy; Chromatography, Liquid; Colonic Neoplasms - drug therapy; Colonic Neoplasms - pathology; Dose-Response Relationship, Drug; Female; Ganoderma - metabolism; Ganoderma applanatum; Glutathione - metabolism; Humans; Inhibitory Concentration 50; Japan; Mass Spectrometry; Mice; Mushroom; Neoplasm Proteins; Secondary Metabolism; Solid Ehrlich tumor; Tumor Suppressor Protein p53 - genetics; Japan; Ganoderma applanatum; Anticancer; Caco-2; Mushroom; Solid Ehrlich tumor; Apoptosis
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.02.058

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 ± 4.08 μg/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 (P ˂ 0.05) at concentrations of 80 and 160 μg/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 μg/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.