ABSTRACT
AIM: To investigate the anti-tumor effects of α-mangostin, a major xanthone identified in the pericarp of mangosteen (Garcinia mangostana Linn), against human gastric adenocarcinoma cells in vitro, and the mechanisms of the effects. METHODS: Human gastric adenocarcinoma cell lines BGC-823 and SGC-7901 were treated with α-mangostin. The cell viability was measured with MTT assay, and cell apoptosis was examined using flow cytometry and TUNEL assay. The expression of the relevant proteins was detected using Western blot. RESULTS: Treatment with α-mangostin (3-10 µg/mL) inhibited the viability of both BGC-823 and SGC-7901 cells in dose- and time-manners. Furthermore, α-mangostin (7 µg/mL) time-dependently increased the apoptosis index of the cancer cells, reduced the mitochondrial membrane potential of the cancer cells, and significantly increased the release of cytochrome c and AIF into cytoplasm. Moreover, the α-mangostin treatment markedly suppressed the constitutive Stat3 protein activation, and Stat3-regulated Bcl-xL and Mcl-1 protein levels in the cancer cells. CONCLUSION: The anti-tumor effects of α-mangostin against human gastric adenocarcinoma cells in vitro can be partly attributed to blockade of Stat3 signaling pathway.
Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Agents, Phytogenic/pharmacology , STAT3 Transcription Factor/antagonists & inhibitors , Stomach Neoplasms/drug therapy , Xanthones/pharmacology , Adenocarcinoma/metabolism , Antineoplastic Agents, Phytogenic/isolation & purification , Apoptosis/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Garcinia mangostana/chemistry , Humans , STAT3 Transcription Factor/metabolism , Signal Transduction/drug effects , Stomach Neoplasms/metabolism , Xanthones/isolation & purificationABSTRACT
OBJECTIVE: To study the role of aquaporin 5(AQP5) in regulating the cell proliferation and apoptosis of human colorectal cancer cells and explore the possible mechanism. METHODS: A small interfering RNA (siRNA) targeting AQP5 was used to suppress endogenous AQP5 expression in the human colorectal cancer cell lines COLO 205 and SW480, and the transfection efficiency of AQP5 siRNA was determined using immunofluorescence assay and PCR. The changes in the proliferation of the transfected cells was evaluated with MTT assay, and the cell apoptosis was analyzed using Annexin V-FITC/PI and TUNEL assays; the changes of Bax and Bcl2 expressions in the cells were determined using RTPCR and Western blotting. RESULTS: Transfection with AQP-5-siRNA resulted in a significant reduction (up to 90%) of AQP-5 expression in COLO 205 and SW480 cells. MTT assay showed that AQP-5-siRNA transfection significantly inhibited the cell proliferation compared NS siRNA transfection (P<0.05). Flow cytometric analysis revealed significantly increased apoptotic rate of cells following AQP-5-siRNA transfection compared with NS?siRNA transfection(P<0.05). Real-time quantitative RT-PCR and Western blotting demonstrated that AQP-5-siRNA transfection significantly increased Bax and Bcl-2 expressions at both mRNA and protein levels in the cells. CONCLUSION: AQP5-siRNA can promote apoptosis of colorectal cancer cells in vitro possibly in relation to its effects on Bax and Bcl expressions.