CARI III inhibits tumor growth in a melanoma-bearing mouse model through induction of G0/G1 cell cycle arrest

Molecules. 2014 Sep 12;19(9):14383-95. doi: 10.3390/molecules190914383.


Mushroom-derived natural products have been used to prevent or treat cancer for millennia. In this study, we evaluated the anticancer effects of CARI (Cell Activation Research Institute) III, which consists of a blend of mushroom mycelia from Phellinus linteus grown on germinated brown rice, Inonotus obliquus grown on germinated brown rice, Antrodia camphorata grown on germinated brown rice and Ganoderma lucidum. Here, we showed that CARI III exerted anti-cancer activity, which is comparable to Dox against melanoma in vivo. B16F10 cells were intraperitoneally injected into C57BL6 mice to develop solid intra-abdominal tumors. Three hundred milligrams of the CARI III/kg/day p.o. regimen reduced tumor weight, comparable to the doxorubicin (Dox)-treated group. An increase in life span (ILS% = 50.88%) was observed in the CARI III-administered group, compared to the tumor control group. CARI III demonstrates anti-proliferative activity against B16F10 melanoma cells through inducing G0/G1 cell cycle arrest. CARI III inhibits the expression of cyclin D1, CDK4 and CDK2 and induces p21. Therefore, CARI III could be a potential chemopreventive supplement to melanoma patients.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects*
  • Cyclin D1 / biosynthesis
  • Cyclin-Dependent Kinase 2 / biosynthesis
  • G1 Phase Cell Cycle Checkpoints / drug effects*
  • Humans
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / pathology
  • Mice
  • Phellinus
  • Plant Extracts
  • Polysaccharides / administration & dosage*
  • Polysaccharides / chemistry
  • Resting Phase, Cell Cycle / drug effects


  • Phellinus linteus extract
  • Plant Extracts
  • Polysaccharides
  • Cyclin D1
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2