title: 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.
abstract: 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.
authors.affiliation: Department of Companion and Laboratory Animal Science, Kongju National University, Yesan-eup, Yesan-gun, Chungnam 340-702, Republic of Korea.
authors.forename: Hae Nim
authors.initials: HN
authors.lastname: Lee
authors.affiliation: Department of Companion and Laboratory Animal Science, Kongju National University, Yesan-eup, Yesan-gun, Chungnam 340-702, Republic of Korea.
authors.forename: Hye Yeon
authors.initials: HY
authors.lastname: Jang
authors.affiliation: Department of Companion and Laboratory Animal Science, Kongju National University, Yesan-eup, Yesan-gun, Chungnam 340-702, Republic of Korea.
authors.forename: Hyeong Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Companion and Laboratory Animal Science, Kongju National University, Yesan-eup, Yesan-gun, Chungnam 340-702, Republic of Korea.
authors.forename: Seong Ah
authors.initials: SA
authors.lastname: Shin
authors.affiliation: Department of Companion and Laboratory Animal Science, Kongju National University, Yesan-eup, Yesan-gun, Chungnam 340-702, Republic of Korea.
authors.forename: Gang Sik
authors.initials: GS
authors.lastname: Choo
authors.affiliation: Department of Companion and Laboratory Animal Science, Kongju National University, Yesan-eup, Yesan-gun, Chungnam 340-702, Republic of Korea.
authors.forename: Young Seok
authors.initials: YS
authors.lastname: Park
authors.affiliation: Department of Companion and Laboratory Animal Science, Kongju National University, Yesan-eup, Yesan-gun, Chungnam 340-702, Republic of Korea.
authors.forename: Sang Ki
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Department of Companion and Laboratory Animal Science, Kongju National University, Yesan-eup, Yesan-gun, Chungnam 340-702, Republic of Korea.
authors.forename: Ji Youn
authors.initials: JY
authors.lastname: Jung
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D018277:Carcinoma, Mucoepidermoid / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005638:Fruit / Q000737:chemistry; D029762:Garcinia mangostana / Q000737:chemistry; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014059:Tongue / Q000187:drug effects / Q000473:pathology; D014062:Tongue Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D044004:Xanthones / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D044004:Xanthones; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases; C021053:mangostin