ABSTRACT
For this study, procyanidins generated through the autoxidation of (-)-epicatechin (Flavan-3-ol) under mildly acidic conditions (pH = 6.0) were characterized with ultra high-performance liquid chromatography (UHPLC) coupled with tandem mass spectrometry (MS/MS). Two procyanidins (types A and B) and a mix of oligomers were generated through the autoxidation of (-)-epicatechin. The antiproliferative activity of this mixture of procyanidins on MDA-MB-231, MDA-MB-436, and MCF-7 breast cancer cells was evaluated. The results indicate that the procyanidin mixture inhibited the proliferation of breast cancer cells, where the activity of the procyanidin mixture was stronger than that of (-)-epicatechin. Moreover, the mechanism underlying the antiproliferative activity of procyanidins was investigated. The resulting data demonstrate that the procyanidins induced apoptotic cell death in a manner selective to cancerous cells. In particular, they caused the activation of intrinsic and extrinsic apoptotic pathways in the breast cancer cells. The findings obtained in this study demonstrate that the generation of procyanidins in vitro by the autoxidation of (-)-epicatechin has potential for the development of anti-breast cancer agents.
ABSTRACT
BACKGROUND: The arrival of large quantities of Sargassum in the Mexican Caribbean Sea has generated major environmental, health and economic problems. Although Sargassum has been used in the generation of some commercial products, few studies have described its possible applications as a source of compounds with anticancer activity. OBJECTIVE: This study aimed to evaluate the antiproliferative effects of different Sargassum extracts on various cancer cell lines. Furthermore, LC/QTOF-MS was used to identify the compounds related to the antiproliferative effect. METHODS: First, determination of the seaweed was performed, and dichloromethane, chloroform and methanol extracts were obtained. The extracts were evaluated for their antiproliferative effects by MTT in breast (MDAMB- 231 and MCF-7), prostate (DU-145), lung (A549) and cervical (SiHa) cancer cell lines. Finally, LC/QTOFMS identified the compounds related to the antiproliferative effect. RESULTS: The authentication showed Sargassum fluitans as the predominant species. The extracts of dichloromethane and chloroform showed an antiproliferative effect. Interestingly, the fractionation of the chloroform extract showed two fractions (FC1 and FC2) with antiproliferative activity in MDA-MB-231, SiHa and A549 cancer cell lines. On the other hand, three fractions of dichloromethane extract (FD1, FD4 and FD5) also showed antiproliferative effects in the MDA-MB-231, MCF-7, SiHa and DU-145 cancer cell lines. Furthermore, LC/QTOF-MS revealed the presence of eight major compounds in FC2. Three compounds with evidence of anticancer activity were identified (D-linalool-3-glucoside, (3R,4S,6E,10Z)-3,4,7,11-tetramethyl-6,10-tridecadienal and alpha-tocotrienol). CONCLUSION: These findings showed that Sargassum fluitans extracts are a possible source of therapeutic agents against cancer and could act as scaffolds for new drug discovery.
ABSTRACT
(-)-Epicatechin is a phenolic compound with antioxidant activity that is present in natural food and drinks, such as cocoa and red wine. Evidence suggests that (-)-epicatechin exhibits anticancer activity; however, its mechanism of action is poorly understood. Here, we investigated the anticancer effects of (-)-epicatechin and its mechanism of action in breast cancer cells. We assessed the anticancer activity by cell proliferation assays, apoptosis by DNA fragmentation and flow cytometry. The expression of proteins associated with apoptosis was analyzed by the human apoptosis array. MitoSOXTM Red and biomarkers of oxidative damage were used to measure the effect of (-)-epicatechin on mitochondrial reactive oxygen species (ROS) and cellular damage, respectively. (-)-Epicatechin treatment caused a decreasing in the viability of MDA-MB-231 and MCF-7 cells. This cell death was associated with DNA fragmentation and an apoptotic proteomic profile. Further, (-)-epicatechin in MDA-MB-231 cells upregulated death receptor (DR4/DR5), increased the ROS production, and modulated pro-apoptotic proteins. In MCF-7 cells, (-)-epicatechin did not involve death receptor; however, an increase in ROS and the upregulation of pro-apoptotic proteins (Bad and Bax) were observed. These changes were associated with the apoptosis activation through the intrinsic pathway. In conclusion, this study shows that (-)-epicatechin has anticancer activity in breast cancer cells and provides novel insight into the molecular mechanism of (-)-epicatechin to induce apoptosis.
