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Gambogic acid (GA) is considered a potent anti-tumor agent for its multiple effects on cancer cells in vitro and in vivo. Low concentrations of GA (0.3-1.2 µmol/L) can suppress invasion of human breast carcinoma cells without affecting cell viability. To get a whole profile of the inhibition on breast cancers, higher concentrations of GA and spontaneous metastatic animal models were employed. Treatment with GA (3 and 6 µmol/L) induced apoptosis in MDA-MB-231 cells and the accumulation of reactive oxygen species (ROS). Furthermore, GA induced PARP cleavage, activation of caspase-3, caspase-8, and caspase-9, as well as an increased ratio of Bax/Bcl-2. Moreover, the translocation of apoptotic inducing factor (AIF) and the release of cytochrome c (Cyt c) from mitochondria were observed, indicating that GA induced apoptosis through accumulation of ROS and mitochondrial apoptotic pathway. GA also inhibited cell survival via blocking Akt/mTOR signaling. In vivo, GA significantly inhibited the xenograft tumor growth and lung metastases in athymic BALB/c nude mice bearing MDA-MB-231 cells. Collectively, these data provide further support for the multiple effects of GA on human breast cancer cells, as well as for its potential application to inhibit tumor growth and prevent metastasis in human cancers. Key words: gambogic acid, human breast cancer, apoptosis, multiple effects, metastasis. L'acide gambogique (AG) est considere comme etant un agent anti-tumoral puissant a cause de ses effets multiples sur les cellules cancereuses in vitro et in vivo. De faibles concentrations d'AG (0,3-1,2 µmol/L) pourraient supprimer l'invasion de cellules de carcinome mammaire chez l'humain sans affecter la viabilite cellulaire. Afin d'avoir une meilleure vue d'ensemble de cette inhibition sur les cancers mammaires, de plus fortes concentrations d'AG et des modeles animaux de metastase spontanee ont ete utilises. Un traitement a l'AG (3 et 6 µmol/L) induisait l'apoptose des cellules MDA-MB231 et l'accumulation d'especes reactives d'oxygene (ERO). De plus, l'AG induisait le clivage de la PARP, l'activation de la caspase-3, de la caspase-8 et de la caspase-9, ainsi qu'une augmentation du rapport Bax/Bcl-2. En outre, la translocation du facteur AIF (<< Apoptotic Inducing Factor >>) et la liberation de cytochrome c (Cyt c) de la mitochondrie ont ete observees, indiquant que l'AG induit l'apoptose par l'intermediaire de l'accumulation d'ERO et de la voie mitochondriale. L'AG inhibait aussi la survie cellulaire en bloquant la voie de signalisation d'Akt/mTor. In vivo, l'AG inhibait significativement la croissance de xenogreffes tumorales et la metastase pulmonaire chez des souris nues BALB/c athymiques porteuses de cellules MDA-MB-231. Dans l'ensemble, ces donnees vont dans le sens des effets multiples de l'AG sur les cellules humaines de cancer du sein, et donnent un appui supplementaire a son utilisation potentielle pour inhiber la croissance tumorale et prevenir la metastase des cancers chez l'humain. Mots-cles : acide gambogique, cancer du sein chez l'humain, apoptose, effets multiples, metastase. [Traduit par la Redaction], Introduction Traditional Chinese medicine has received increasing attention from oncologists recently. Gambogic acid (GA, [C.sub.38][H.sub.44][O.sub.8], Fig. 1A) is a polyprenylated xanthone isolated from the gamboge resin of Garcinia hanburryi tree [...]

We recently established that LYG-202, a new flavonoid with a piperazine substitution, exerts an anti-tumor effect in vivo and in vitro. In the present study, we demonstrate that LYG-202 induces G1/S phase arrest and apoptosis in human colorectal carcinoma HCT-116 cells. Data showed that the blockade of the cell cycle was associated with increased p21WAF1/Cip1 and Rb levels and reduced expression of cyclin D1, cyclin E, and CDK4. Moreover, PARP cleavage, activation of caspase-3, caspase-8, and caspase-9, and an increased ratio of Bax/Bcl-2 were detected in LYG-202-induced apoptosis. Additionally, activation of p53 resulted in the up-regulation of its downstream targets PUMA and p21WAF1/Cip1, as well as the down-regulation of its negative regulator MDM2, suggesting that the p53 pathway may play a crucial role in LYG-202-induced cell cycle arrest and apoptosis. Furthermore, siRNA knockdown of p53 attenuated the G1 cell cycle arrest and apoptosis induced by LYG-202, as the effects of LYG-202 on up-regulation of p21WAF1/Cip1 and down-regulation of Bcl-2 and pro-caspase-3 were partly inhibited in p53 siRNA transfected cells compared with control siRNA transfected cells. Collectively, these data indicate that LYG-202 exerts its anti-tumor potency by activating the p53-p21 pathway for G1/S cell cycle arrest and apoptosis in colorectal cancer cells. [ABSTRACT FROM AUTHOR]

Highlights: [•] LL-202 inhibited the growth and proliferation of MCF-7 cells in a concentration- and time-dependent manner. [•] LL-202 induced apoptosis and G2/M phase arrest in MCF-7 cells. [•] NAC partly blocked LL-202-induced ROS levels and apoptosis. [•] LL-202 significantly suppressed the growth of MCF-7 breast cancer xenograft tumors with low systemic toxicity. [ABSTRACT FROM AUTHOR]

Abstract: Wogonin, a naturally occurring monoflavonoid extracted from the root of Scutellaria baicalensis Georgi, has been reported for its anti-oxidant activity. However, it is still unclear whether wogonin can inhibit oxidant-induced vascular permeability. In this study, we evaluated the effects of wogonin on H2O2-induced vascular permeability in human umbilical vein endothelial cells (HUVECs). We found that wogonin can suppress the H2O2-stimulated actin remodeling and albumin uptake of HUVECs, as well as transendothelial cell migration of the human breast carcinoma cell MDA-MB-231. The mechanism revealed that wogonin inhibited H2O2-induced phosphorylation of caveolin-1 (cav-1) associating with the suppression of stabilization of VE-cadherin and β-catenin. Moreover, wogonin repressed anisomycin-induced phosphorylation of p38, cav-1 and vascular permeability. These results suggested that wogonin could inhibit H2O2-induced vascular permeability by downregulating the phosphorylation of cav-1, and that it might have a therapeutic potential for the diseases associated with the development of both oxidant and vascular permeability. [Copyright &y& Elsevier]

VI-16, a newly synthesized flavonoid, has a hydroxy substitution at C5 position, a methoxyl substitution at C5 position, and a piperazine substitution at C7 position. Here, we firstly investigated the potential antitumor effect of VI-16 in HepG2 human hepatocarcinoma cells. The MTT assay showed that VI-16 inhibited HepG2 cell growth in a concentration- and time-dependent manner. To further investigate whether apoptosis induction contributed to the antitumor effects of VI-16, DAPI staining and Annexin-V/PI double staining were performed in our tests. The data showed that VI-16 could induce apoptotic cell death in HepG2 cells. Moreover, mechanistic studies revealed that VI-16-induced apoptosis was a caspase-dependent process by decreasing the expression of pro-caspase-3. The changes in the expression of caspase-8, capsase-9, Bax and bcl-2 after VI-16 treatment suggested that the mitochondrial pathway was involved in the apoptosis induced by VI-16. Furthermore, VI-16 could significantly increase the loss of mitochondrial membrane potential and the expression of p53. Taken together, these results demonstrated that apoptosis induced by VI-16 might be one of the mechanisms by which VI-16 acts as a preventive antitumor drug against human hepatoma.