SB-120, a supercritical extract of the herb Scutelaria barbata, is a candidate oral drug that has shown promising efficacy and excellent safety in the early phase clinical trials for advanced breast cancer. SB-120 is selectively cytotoxic to cancer cells while sparing non-transformed cells.      

SB-120 selectively targets cancer cell mitochondria, and is distinguished from other such drugs by its ability to induce not only inhibition of OXPHOS but also of glycolysis.      

Chen V, Staub RE, Fong S, Tagliaferri M, Cohen I, Shtivelman E. PLoS One. 2012;7(2):e30300. doi: 10.1371/journal. pone.0030300.*

Scutellaria barbata (acqueous extract) SB selectively targets mitochondria of cancer cells to inhibit glycolysis and OXPHOS.      

Chen V, Staub RE, Fong S, Tagliaferri M, Cohen I, Shtivelman E. PLoS One. 2012;7(2):e30300. doi: 10.1371/journal.pone.0030300. SB is a candidate oral drug that has shown promising efficacy and excellent safety in the early phase clinical trials for advanced breast cancer. We have reported previously that SB was selectively cytotoxic to cancer cells while sparing non-transformed cells. In tumor, but not in non-transformed cells, SB induced generation of ROS and severe DNA damage followed by hyperactivation of PARP, depletion of the cellular ATP and NAD, and inhibition of glycolysis.      

We show here that tumor cells' mitochondria are the primary source of reactive oxygen species induced by SB. Treatment with SB induces progressively higher levels of mitochondrial superoxide as well as peroxide-type ROS. Inhibition of mitochondrial respiration prevents generation of both types of ROS and protects cells from SB-induced death. In addition to glycolysis, SB inhibits oxidative phosphorylation in tumor cells and depletes mitochondrial reserve capacity depriving cells of the ability to produce ATP.      

Tumor cells lacking functional mitochondria maintain glycolytic activity in presence of SB thus supporting the hypothesis that mitochondria are the primary target of SB. The metabolic effects of SB towards normal cells are not significant, in agreement with the low levels of oxidative damage that SB inflicts on them. SB is therefore a drug that selectively targets cancer cell mitochondria, and is distinguished from other such drugs by its ability to induce not only inhibition of OXPHOS but also of glycolysis. This study provides a better understanding of the mechanism of SB's cytotoxicity, and the basis of its selectivity towards cancer cells.

Scutellaria barbata (acqueous extract) SB selectively targets mitochondria of cancer cells to inhibit glycolysis and OXPHOS.      

Chen V, Staub RE, Fong S, Tagliaferri M, Cohen I, Shtivelman E. PLoS One. 2012;7(2):e30300. doi: 10.1371/journal.pone.0030300. SB is a candidate oral drug that has shown promising efficacy and excellent safety in the early phase clinical trials for advanced breast cancer. We have reported previously that SB was selectively cytotoxic to cancer cells while sparing non-transformed cells. In tumor, but not in non-transformed cells, SB induced generation of ROS and severe DNA damage followed by hyperactivation of PARP, depletion of the cellular ATP and NAD, and inhibition of glycolysis.      

We show here that tumor cells' mitochondria are the primary source of reactive oxygen species induced by SB. Treatment with SB induces progressively higher levels of mitochondrial superoxide as well as peroxide-type ROS. Inhibition of mitochondrial respiration prevents generation of both types of ROS and protects cells from SB-induced death. In addition to glycolysis, SB inhibits oxidative phosphorylation in tumor cells and depletes mitochondrial reserve capacity depriving cells of the ability to produce ATP.      

Tumor cells lacking functional mitochondria maintain glycolytic activity in presence of SB thus supporting the hypothesis that mitochondria are the primary target of SB. The metabolic effects of SB towards normal cells are not significant, in agreement with the low levels of oxidative damage that SB inflicts on them. SB is therefore a drug that selectively targets cancer cell mitochondria, and is distinguished from other such drugs by its ability to induce not only inhibition of OXPHOS but also of glycolysis. This study provides a better understanding of the mechanism of SB's cytotoxicity, and the basis of its selectivity towards cancer cells.

References

1. Chen V, Staub RE, Fong S, Tagliaferri M, Cohen I, Shtivelman E. PLoS One. 2012;7(2):e30300. doi: 10.1371/journal. pone.0030300.

2. Lee, Tae-Kyun, et al. "Inhibitory effects of Scutellaria barbata D. Don on human uterine leiomyomal smooth muscle cell proliferation through cell cycle analysis."Int Immunopharmacol 4.3 (2004): 447-454.

3. Wong, Brian YY, et al. "Oldenlandia diffusa and Scutellaria barbata augment macrophage oxidative burst and inhibit tumor growth." Cancer biotherapy & radiopharmaceuticals 11.1 (1996): 51-56.

4. Kim, Dong-Il, et al. "Regulation of IGF-I production and proliferation of human leiomyomal smooth muscle cells by Scutellaria barbata D. Don in vitro: isolation of flavonoids of apigenin and luteolin as acting compounds." Toxicology and applied pharmacology 205.3 (2005): 213-224.