Antitumor and apoptosis-inducing effects of α-mangostin extracted from the pericarp of the mangosteen fruit (Garcinia mangostana L.)in YD-15 tongue mucoepidermoid carcinoma cells

Int J Mol Med. 2016 Apr;37(4):939-48. doi: 10.3892/ijmm.2016.2517. Epub 2016 Mar 4.


α-mangostin is a dietary xanthone which has been shown to have antioxidant, anti-allergic, antiviral, antibacterial, anti-inflammatory and anticancer effects in various types of human cancer cells. In the present study, we aimed to elucidate the molecular mechanisms responsible for the apoptosis-inducing effects of α-mangostin on YD-15 tongue mucoepidermoid carcinoma cells. The results from MTT assays revealed that cell proliferation significantly decreased in a dose-dependent manner in the cells treated with α-mangostin. DAPI staining illustrated that chromatin condensation in the cells treated with 15 µM α-mangostin was far greater than that in the untreated cells. Flow cytometric analysis indicated that α-mangostin suppressed YD-15 cell viability by inducing apoptosis and promoting cell cycle arrest in the sub-G1 phase. Western blot analysis of various signaling molecules revealed that α-mangostin targeted the extracellular signal‑regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) signaling pathways through the inhibition of ERK1/2 and p38 phosphorylation in a dose‑dependent manner. α-mangostin also increased the levels of Bax (pro-apoptotic), cleaved caspase-3, cleaved caspase-9 and cleaved-poly(ADP-ribose) polymerase (PARP), whereas the levels of the anti-apoptotic factors, Bcl-2 and c-myc, decreased in a dose-dependent manner. The anticancer effects of α-mangostin were also investigated in a tumor xenograft mouse model. The α-mangostin-treated nude mice bearing YD-15 tumor xenografts exhibited a significantly reduced tumor volume and tumor weight due to the potent promoting effects of α-mangostin on cancer cell apoptosis, as determined by TUNEL assay. Immunohistochemical analysis revealed that the level of cleaved caspase-3 increased, whereas the Ki-67, p-ERK1/2 and p-p38 levels decreased in the α-mangostin‑treated mice. Taken together, the findings of our study indicate that α-mangostin induces the apoptosis of YD-15 tongue carcinoma cells through the ERK1/2 and p38 MAPK signaling pathways.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Apoptosis / drug effects
  • Carcinoma, Mucoepidermoid / drug therapy*
  • Carcinoma, Mucoepidermoid / metabolism
  • Carcinoma, Mucoepidermoid / pathology
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Enzyme Activation / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Fruit / chemistry
  • Garcinia mangostana / chemistry
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Tongue / drug effects
  • Tongue / pathology
  • Tongue Neoplasms / drug therapy*
  • Tongue Neoplasms / metabolism
  • Tongue Neoplasms / pathology
  • Xanthones / isolation & purification
  • Xanthones / pharmacology
  • Xanthones / therapeutic use*
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Antineoplastic Agents, Phytogenic
  • Xanthones
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Caspases
  • mangostin