Abstract
Scutellaria baicalensis is a widely used Chinese herbal medicine historically used in antiinflammatory and anticancer therapy. The goals of the study were to 1) determine its in vitro and in vivo anti-prostate cancer activity, 2) investigate its molecular mechanism directed at cell proliferation control including cyclooxygenase-2(COX-2) prostaglandin E 2 (PGE 2 ) and cyclins/cdks pathways, and 3) compare it with those of PC-SPES (PC stands for prostate cancer and spes is Latin for hope), a former herbal mixture for prostate cancer treatment of which S. baicalensis is a major constituent. Two human prostate cancer cell lines (LNCaP, androgen dependent, and PC-3, androgen independent) were assessed for growth inhibition. S. baicalensis exerted dose- and time-dependent increased growth inhibition in both cell lines. However, the PC-3 cells IC50 (50% growth inhibition concentration) were slightly more sensitive than LNCaP cells (IC 50 = 0.15 mg/ml), although the former is androgen independent. S. baicalensis was more effective in inhibition of cell growth compared with PC-SPES (IC 50 = 0.38 mg/ml for PC-3 cells). Significant reduction of PGE 2 synthesis in both cells after treatment with S. baicalensis resulted from direct inhibition of COX-2 activity rather than COX-2 protein suppression. S. baicalensis also inhibited prostate-specific antigen production in LNCaP cells. Finally, S. baicalensis suppressed expression of cyclin D1 in LNCaP cells, resulting in a G 1 phase arrest, while inhibiting cdk1 expression and kinase activity in PC-3 cells, ultimately leading to a G 2 /M cell cycle arrest. Animal studies showed a 50% reduction in tumor volume after a 7-wk treatment period. This study demonstrated that S. baicalensis may be a novel anticancer agent for the treatment of prostate cancer.
Acknowledgments and Notes
This work was partially supported by an NIH/NCCAM grant (AT00739) to D.Y.Z.
Address correspondence to D. Y. Zhang, Molecular Pathology Laboratory, Mount Sinai School of Medicine, Box 1122, One Gustave L. Levy Place, New York, New York 10029. Phone: 212-659-8173. FAX: 212-427-2082. E-mail: [email protected]