Scutellaria barbata was used in women with metastatic breast cancer (MBC). The trial was an open-label, phase 1B, multicenter, dose escalation study. Eligible patients had histologically confirmed breast cancer and measurable stage IV disease.

Investigator assessment classified three patients with stable disease for >120 days (21%). One patient was on Scutellaria barbata for 449 days and remains stable for 700 + days. Independent radiology review identified three patients with objective tumor regression (Perez et al., 2010).

Scutellaria barbata (aqueous 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

Chen V, Staub RE, Fong S, Tagliaferri M, Cohen I, Shtivelman E. Bezielle (Scutellaria barbata) Selectively Targets Mitochondria of Cancer Cells to Inhibit Glycolysis and OXPHOS PLoS One. 2012;7(2):e30300. doi: 10.1371/journal. pone.0030300.

Perez AT, Arun B, Tripathy D, Tagliaferri MA, Shaw HS, Kimmick GG, Cohen I, Shtivelman E, Caygill KA, Grady D, Schactman M, Shapiro CL. A phase 1B dose escalation trial of Scutellaria barbata (BZL101) for patients with metastatic breast cancer. Breast Cancer Res Treat. 2010 Feb;120(1):111-8. doi: 10.1007/s10549-009-0678-5.