Surfactin from Bacillus subtilis displays anti‐proliferative effect via apoptosis induction, cell cycle arrest and survival signaling suppression

Abstract

The effect of surfactin on the proliferation of LoVo cells, a human colon carcinoma cell line, was examined. Surfactin strongly blocked the proliferation of LoVo cells by inducing pro-apoptotic activity and arresting the cell cycle, according to several lines of evidence on DNA fragmentation, Annexin V staining, and altered levels of poly (ADP-ribose) polymerase, caspase-3, p21 WAF1/Cip1 , p53, CDK2 and cyclin E. The anti-proliferative activity of surfactin was mediated by inhibiting extracellular-related protein kinase and phosphoinositide 3-kinase/ Akt activation, as assessed by phosphorylation levels. Therefore, our data suggest that surfactin may have anti-cancer properties as a result of its ability to downregulate the cell cycle and suppress its survival.

Effect of themicrobial lipopeptide on tumor cell lines: apoptosis induced by disturbing the fatty acid composition of cell membrane

“…Surfactin also induces apoptosis of MCF-7 cell lines through a ROS/ JNK-mediated mitochondrial/caspase pathway (Cao et al, 2010). Our results that lipopeptides inhibited the growth of Bcap-37 cells by inducing apoptosis were consistent with the findings of Kim (2007) and other authors (Wang et al, 2007). It is worthy to note that surfactin inhibits many enzymes or lipopolysaccharides that are located in the cellular membrane.…”

“…Combined with our present work, it can be concluded that surfactin-like lipopeptides at a concentration of 20- Recently, surfactin has been reported to induce the apoptosis of LoVo (human colon carcinoma cell line) and MCF-7 (human breast cancer cell line) cancer cells, and the mechanisms of surfactin induced apoptosis on cancer cell lines have been investigated on the molecular level (Kim et al, 2007;Cao et al, 2009aCao et al, , b, c, 2010. For example, the apoptosis of LoVo cells induced by surfactin was mediated by inhibiting extracellular-related protein kinase and phosphoinositide 3-kinase/akt activation, as assessed by phosphorylation levels (Kim et al, 2007). It was reported that the apoptosis effects of surfactin on MCF-7 cell lines were associated with caspase-3 (Cao et al, 2009b).…”

“…The 50% cytotoxic concentrations of surfactin for the adhesive and nonadhesive cell lines were as follows: ML, 40 μmol/L; 293, 30 μmol/L; Hep2, 42 μmol/L; CV1, 50 μmol/L; Molt 4/8, 35 μmol/L; MT-4, 30 μmol/L; and H9, 43 μmol/ L (Vollenbroich et al, 1997). The IC 50 of surfactin on LoVo cells was about 60 μmol/L after treated 24 h (Kim et al, 2007), and in addition, a new cyclic lipopeptide inhibited proliferation in K562 cells with an IC 50 value approximately to 30 μg/mL (Wang et al, 2007). Combined with our present work, it can be concluded that surfactin-like lipopeptides at a concentration of 20- Recently, surfactin has been reported to induce the apoptosis of LoVo (human colon carcinoma cell line) and MCF-7 (human breast cancer cell line) cancer cells, and the mechanisms of surfactin induced apoptosis on cancer cell lines have been investigated on the molecular level (Kim et al, 2007;Cao et al, 2009aCao et al, , b, c, 2010.…”

“…The IC 50 of surfactin on LoVo cells was about 60 μmol/L after treated 24 h (Kim et al, 2007), and in addition, a new cyclic lipopeptide inhibited proliferation in K562 cells with an IC 50 value approximately to 30 μg/mL (Wang et al, 2007). Combined with our present work, it can be concluded that surfactin-like lipopeptides at a concentration of 20- Recently, surfactin has been reported to induce the apoptosis of LoVo (human colon carcinoma cell line) and MCF-7 (human breast cancer cell line) cancer cells, and the mechanisms of surfactin induced apoptosis on cancer cell lines have been investigated on the molecular level (Kim et al, 2007;Cao et al, 2009aCao et al, , b, c, 2010. For example, the apoptosis of LoVo cells induced by surfactin was mediated by inhibiting extracellular-related protein kinase and phosphoinositide 3-kinase/akt activation, as assessed by phosphorylation levels (Kim et al, 2007).…”

“…Many of these molecules with membrane active properties play an important role in the apoptosis induction process of tumor cells. For example, surfactin, a cyclic lipopeptide produced by Bacillus subtilis (Arima et al, 1968), is well-known for its antitumor activity on Ehrlich carcinoma tumor cells and LoVo cells (Kameda et al, 1974;Kim et al, 2007). In addition, surfactin can cause membrane leakage through pore formation (Grau et al, 1999), ion channel formation (Sheppard et al, 1991), action as a cation carrier (Sheppard et al, 1991) and detergent like effects (Heerklotz and Seelig, 2001), all of which eventually lead to cytotoxic effects.…”