Dr. Xiao-Ming Yin is professor at the Department of Pathology in the University of Pittsburgh School of Medicine. From 1998 to present Dr. Yin has been a member of the Molecular Oncology Program at the University of Pittsburgh Cancer Institute in Pittsburgh, PA. He has also been the Attending Physician, Assistant Director, and Associate Director of the Division of Molecular Diagnostics in the Department of Pathology at the University of Pittsburgh Medical Center.
He is a member of: American Society for Biochemistry and Molecular Biology; American Society for Investigative Pathology, American Association for the Study of Liver Diseases, Association of Molecular Pathology, and Academy of Clinical Laboratory Physicians and Scientists. Dr. Yin received his M.D. in 1982 and his M.S. in Immunology in 1985 from Shanghai Medical University, Shanghai. After earning his PhD in 1991 studying Immunology from the University of Texas Southwestern, he did his post-doctoral work at theHoward Hughes Medical Institute of Washington University. From 1995-1998, Dr. Xiao-Ming did his residency work in Pathology at Washington University, St. Louis, MO. In 1996 he recieved the National Research Service Award, NIH and in 1997 received the Howard Temin Award, NCI, NIH.
Anthocyanidins and Cancer Therapy, Different Routes to the Demise
Rentian Feng, Hong-Min Ni, Shiow Y. Wang and Xiao-Ming Yin
Department of Pathology, University of Pittsburgh School of Medicine
The Fruit Laboratory, Beltsville Agriculture Research Center, US DOA, Beltsville, MD 20705
3550 Terrace Street, Pittsburgh, PA 15261
Anthocyanidins have broad biological activities. We have studied two anthocyanindins, cyanidin and delphinidin, for their biological effects on affecting cancer cell survival. We found that cyanidin-3-rutinoside (C-3-R) purified from the black raspberry induced apoptosis in human leukemic cells, HL-60 cells, in a dose- and time-dependent manner.
Interestingly, despite that it presented anti-oxidant activity in vitro, C-3-R manifested an oxidant activity in the leukemic cells by inducing the accumulation of peroxides, which activated the stress kinases, p38 MAPK and JNK. These kinases were important for the activation of the mitochondria apoptosis pathway via the pro-death BH3-only molecule, Bim. Down-regulation of Bim or overexpression of Bcl-2 or Bcl-xL considerably blocked apoptosis.
Notably, cyanidin-3-rutinoside treatment did not lead to increased ROS accumulation in normal human peripheral blood mononuclear cells and had no cytotoxic effects on these cells. These results indicate that C-3-R has the potential to be used in leukemia therapy with the advantages of being selective against tumors. Interestingly, another anthocyanidin, delphinidin, extracted from billberry, caused a very different phenotype in hepatocellular carcinoma cells (HCCs). Here delphididin did not induce significant cell death, but caused extensive intracellular vacuolization.
Further studies showed that delphinidin could induce autophagy. Autophagy is an evolutionarily conserved intracellular degradation mechanism. When autophagy was inhibited, the cytotoxicity of delphinidin was then demonstrated. Thus it seemed that autophagy here protect the cells from delphinidin-induced cell death. In contrast to C-3-R-induced apoptosis in leukemic cells, cell death induced by delphinidin in HCCs was not apoptotic, but likely necrotic. It would be important to characterize the mechanism of this type of necrotic death in future studies. In summary, different anthocyanidins could induce different cell death mechanisms in different tumor cells, which may be explored for tumor-specific therapy.