A cells growth. Combining the results from Fig. 4, these results suggest
A cells growth. Combining the results from Fig. 4, these results suggest that decreasing cellular oxidative stress could through inhibiting glycolytic activity PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26080418 in tumor cells inhibit tumor cells growth. Moreover, -LA was shown to inhibit SMMC7721 hepatoma cells growth in a dosedependent manner (Fig. 6b), and in a certain dose (2.5 mM and 5 mM) -LA induced hepatoma cell apoptosis (Fig. 6c). However, the same concentration of -LA has no obvious effect on immortalized normal L02 liver cells. This suggests that oxidative stress in hepatoma cells can be exploited to selectively kill cancer cells. In keeping with the results of the in vitro experiments, nude mice injected with SMMC-7721 hepatoma cells formed bigger xenograft tumors than those injected with SOD-7721 cells. As shown in Fig. 6d, mice injected with SMMC-7721 cells start to form visible tumor by 5 days (about 1 mm) with subsequent rapid growth. Mice injected with SOD-7721 cells start to form tumor at about 10?5 days, and the tumors grow slowly. Apart from SOD-cells resulting in a delay in tumor formation in nude mice, it also gives rise to significantly smaller tumors than SMMC-7721 cells as judged by total tumor mass (Fig. 6e). These results from xenograft tumors confirm that reduction of oxidative level in tumor cells could inhibit tumor growth.Meanwhile, the measurement of relative LDL activity showed that cellular glycolytic activity is related to the ROS stress level. Paralleled with the change of ROS level (Fig. 5a), LDH activities in each cell lines displayed in different levels (Fig. 5b). SOD-AS7721 which has the highest ROS level, accordingly displayed the highest LDH activity. However, SOD-7721 and L02 cells which have relative lower levels of ROS, exhibited significantly lower levels of LDH activity compared to SMMC-7721 cells. This confirms that ROS can regulate glycolytic activity independently of hypoxia.Decreasing cellular oxidative stress inhibits tumor growth in vitro and in vivo We further tested whether the change of cellular oxidative states could influence tumor growth. Olumacostat glasaretil site Either antioxidant LA treatment or MnSOD transfection were used to scav-DiscussionThe Warburg effect is the basis for the widespread application of positron emission tomography, established in the mid 1990s, in which a glucose analog tracer is used to differentiate normal and tumor tissue, as tumor tissue takes up glucose more avidly [23]. The Warburg effect has been observed in various tumor cells, including solid tumors and leukemia, and is recognized to represent a prominent metabolic characteristic of malignant cells [24]. At present several possible mechanisms have been proposed to explain this metabolic difference of tumor cells. ThesePage 6 of(page number not for citation purposes)Molecular Cancer 2009, 8:http://www.molecular-cancer.com/content/8/1/Figure 3 (see legend on next page)Page 7 of(page number not for citation purposes)Molecular Cancer 2009, 8:http://www.molecular-cancer.com/content/8/1/Figure 3 endogenous ROS Enhanced (see previous page) up-regulate glycolytic activity Enhanced endogenous ROS up-regulate glycolytic activity. (a) Quantification of ROS levels in SMMC-7721 cells in comparison with their XO-transfected cells. SMMC-7721 cells were transfected with a void vector (XO-) or a vector expressing XO (XO+) as described in “Materials and methods”. In some cases XO+ cells were treated with 5 mM -LA for 24 h. ROS levels were measured by DCF fluorescence using flow cytometry a.