Griffipavixanthone
Griffipavixanthone inhibits the growth of human Non-small-cell lung cancer H520 cells in dose- and time-dependent manners, it induces cell apoptosis through mitochondrial apoptotic pathway accompanying with ROS production. It can inhibit tumor metastasis and proliferation via downregulation of the RAF pathway in esophageal cancer.
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Molecules. 2014 Jan 27;19(2):1422-31.
Griffipavixanthone from Garcinia oblongifolia champ induces cell apoptosis in human non-small-cell lung cancer H520 cells in vitro.[Pubmed:
24473206]
Griffipavixanthone (GPX) is a dimeric xanthone which was isolated in a systematic investigation of Garcinia oblongifolia Champ. In this study, we investigate the effect of Griffipavixanthone on cell proliferation and apoptosis on human Non-small-cell lung cancer (NSCLC) cells in vitro and determine the mechanisms of its action.
METHODS AND RESULTS:
Griffipavixanthone inhibited the growth of H520 cells in dose- and time-dependent manners, with IC50 values of 3.03 ± 0.21 μM at 48 h. In addition, Annexin V/PI double staining assay revealed that cells in early stage of apoptosis were significantly increased upon Griffipavixanthone treatment dose-dependently. Rh123 staining assay indicated that Griffipavixanthone reduced the mitochondrial membrane potential. DCFH-DA staining revealed that intracellular ROS increased with Griffipavixanthone treatment. Moreover, Griffipavixanthone cleaved and activated caspase-3.
CONCLUSIONS:
In summary, this study showed that Griffipavixanthone inhibited H520 cell proliferation in dose- and time-dependent manner. Further mechanistic study indicated that Griffipavixanthone induced cell apoptosis through mitochondrial apoptotic pathway accompanying with ROS production. Our results demonstrate the potential application of Griffipavixanthone as an anti-non-small cell lung cancer agent.
Oncotarget. 2016 Jan 12; 7(2): 1826–1837.
Griffipavixanthone, a dimeric xanthone extracted from edible plants, inhibits tumor metastasis and proliferation via downregulation of the RAF pathway in esophageal cancer.[Pubmed:
26646323 ]
Metastasis causes a large number of deaths among esophageal cancer patients. The activation of RAF family proteins elevates tumor metastasis and proliferation.
METHODS AND RESULTS:
In screen targeting the RAF protein, we identified that Griffipavixanthone (GPX), a dimeric xanthone isolated from Garcinia esculenta, is a B-RAF and C-RAF inhibitor against esophageal cancer cells. Using wound healing, transwell migration and matrigel invasion assays, we confirmed that GPX significantly inhibited cell migration and invasion. Furthermore, exposure to GPX rendered cell proliferation and induced G2/M cell cycle arrest. Our mechanistic study showed that GPX suppressed cancer metastasis and proliferation through downregulation of RAF-MEK-ERK cascades proteins as well as RAF mRNA levels. In a pulmonary metastasis model, the intraperitoneal injection of GPX significantly suppressed esophageal tumor metastasis and ERK protein level in vivo.
CONCLUSIONS:
In conclusion, our present study suggested that GPX could inhibit tumor migration, invasion and proliferation in vitro and in vivo, which indicated the potential of GPX for preventing and treating esophageal cancer.
