Role of manganese superoxide dismutase on growth and invasive properties of human estrogen-independent breast cancer cells

Abstract

Manganese superoxide dismutase (MnSOD) is known to play a role in cancer. MnSOD exerts a tumor suppressive effect in estrogen-dependent human breast cancer cells. In the present study we investigated the in vitro role of MnSOD in the growth of some aggressive and highly metastatic estrogen-independent breast cancer cells, i.e., MDA-MB231 and SKBR3 cells. We show that estrogen-independent cells expressed a significantly higher basal MnSOD level compared to estrogen-dependent human breast cancer cell lines (MCF-7 and T47D). For MDA-MB231 cells, the high-MnSOD level was accompanied by an overproduction of intracellular hydrogen peroxide (H2O2) and by a low expression of the major H2O2-detoxifying enzymes, catalase, and peroxiredoxin 3, compared to MCF-7 cells. Suppression of MnSOD expression by antisense RNA was associated with a decrease of H2O2 content and caused a stimulation of growth with a reduced cell doubling time but induced a decrease of colony formation. Furthermore, treatment of MDA-MB231 cells with H2O2 scavengers markedly reduced tumor cell growth and colony formation. In addition, MnSOD suppression or treatment with H2O2 scavengers reduced the invasive properties of MDA-MB231 cells up to 43%, with a concomitant decrease of metalloproteinase-9 activity. We conclude that MnSOD plays a role in regulating tumor cell growth and invasive properties of estrogen-independent metastatic breast cancer cells. These action are mediated by MnSOD-dependent H2O2 production. In addition, these results suggest that MnSOD up-regulation may be one mechanism that contributes to the development of metastatic breast cancers.

MnSOD Promotes Tumor Invasion via Upregulation of FoxM1–MMP2 Axis and Related with Poor Survival and Relapse in Lung Adenocarcinomas

“…MnSOD may also function as a tumor suppressor; for example, it may reduce growth of tumors associated with melanoma (2), pancreatic adenocarcinoma (3,4), colorectal cancer (5), ovarian cancer (6), breast cancer (7), and multiple myeloma (8). Conversely, MnSOD may promote tumor progression in cancers, such as fibrosarcoma (9), gastric cancer (10,11), glioblastoma (12), T-cell lymphoma (13), breast cancer (14,15), cervical cancer (16), prostate cancer (17), and lung cancer (18). Therefore, the precise role of MnSOD in tumorigenesis remains elusive.…”

Antitumor and Antiangiogenic Effects of the Crude Oil of Nigella sativa L. in Tumor Tissues in BALB/c Mice

“…As mentioned earlier, oxidative stress is the result of what aerobic life greatly depends on oxidation. While aerobic cells enjoy this energy-producing reaction, they need to fight its harmful products at the same time [1]. To do so, organisms apply compound systems of antioxidants.…”

“…Enzymes such as CAT and SOD are antioxidants essentially required for cells' self-protection. They are key players in several reactions which prevent and treat the harms of oxidative stress [1]. The members of the SOD family dismutate su- shows the quantified data, as mean ± SD, through densitometric analysis.…”

“…It has been reported that cancer cells differ from normal ones in ROS production and enzymatic antioxidant activity. ROS production is much greater in cancer cells [1]. There is also a noticeable imbalance in the activity of antioxidant enzymes.…”

Relative Transcription Expression Level of SIRT1, SIRT2 and SIRT3 in Correlation to the Expression of a Set of Selected Cancer Related Genes in Human Breast Cancer

“…Huang et al (2007) suggested that SOD can act as a tumor suppressor by decreasing growth and survival of breast cancer cells. On the other hand, some studies have reported a correlation between high SOD level and invasiveness of breast cancer (Tsanou et al, 2004;Kattan et al, 2008). Er et al (2004) speculated that upregulation of SOD expression induced by oxidative stress or local inflammation may contribute a selective growth advantage to tumor cells compared to their normal counterparts (Khan et al, 2010).…”