title: Ganodermanontriol, a lanostanoid triterpene from Ganoderma lucidum, suppresses growth of colon cancer cells through ß-catenin signaling.
abstract: Colorectal cancer is one of the most common cancers in men and women in the world. Previous molecular studies have revealed that deregulation of the ß-catenin signaling pathway plays a crucial role in the progression of colorectal cancer. Therefore, modulation of the ß-catenin pathway offers a strategy to control colorectal cancer progression. The medicinal mushroom Ganoderma lucidum (GL) is a rich source of triterpenes with anticancer properties. Here, we show that ganodermanontriol (GNDT), a purified triterpene from GL, inhibited proliferation of HCT-116 and HT-29 colon cancer cells without a significant effect on cell viability. Moreover, GNDT inhibited transcriptional activity of ß-catenin and protein expression of its target gene cyclin D1 in a dose-dependent manner. A marked inhibition effect was also seen on Cdk-4 and PCNA expression, whereas expression of Cdk-2, p21 and cyclin E was not affected by the GNDT treatment. In addition, GNDT caused a dose-dependent increase in protein expression of E-cadherin and ß-catenin in HT-29 cells. Finally, GNDT suppressed tumor growth in a xenograft model of human colon adenocarcinoma cells HT-29 implanted in nude mice without any side-effects and inhibited expression of cyclin D1 in tumors. In conclusion, our data suggest that ganodermanontriol might be a potential chemotherapeutic agent for the treatment of cancer.
authors.affiliation: Cancer Research Laboratory, Methodist Research Institute, Indianapolis, IN 46202, USA.
authors.forename: Andrej
authors.initials: A
authors.lastname: Jedinak
authors.forename: Anita
authors.initials: A
authors.lastname: Thyagarajan-Sahu
authors.forename: Jiahua
authors.initials: J
authors.lastname: Jiang
authors.forename: Daniel
authors.initials: D
authors.lastname: Sliva
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008819:Mice, Nude; D020940:Reishi / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000378:metabolism / Q000502:physiology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014315:Triterpenes; D051176:beta Catenin; C558586:ganodermanontriol; C497083:lanostanoid; C050247:ganodermatriol; D007810:Lanosterol