Flavopiridol, apoptosis induction

Parker BW, Kaur G, Nieves-Neira W, et al. Early induction of apoptosis in hematopoietic cell lines after exposure to flavopiridol. Blood 1998 91 458-465. 

Brusselbach S, Nettelbeck DM, Sedlacek HH, Muller R. Cell cycle-independent induction of apoptosis by the anti-tumor drug flavopiridol in endothelial cells. Int J Cancer 1998 77 146-152. 

Similar interactions have been observed with the CDK inhibitor flavopiridol. Initial studies demonstrated that flavopiridol interacted synergistically with TNF to induce apoptosis in lung cancer cells. Subsequently, it was shown that co-administration of TRAIL with flavopiridol resulted in a marked increase in mitochondrial damage and apoptosis in other tumor cell types (Senderowicz 1999 Rosato et al. 2004). Given evidence that flavopiridol acts at least in part to induce apoptosis in tumor cells via induction of mitochondrial injury, it seems plausible to propose that the potent tu-moricidal effects of a regimen combining TRAIL with flavopiridol, as in the case of HDACIs, stems from simultaneous activation of the intrinsic and extrinsic apoptotic pathways. 

Almenara I, Rosato R, Grant S (2002) Synergistic induction of mitochondrial damage and apoptosis in human leukemia cells by flavopiridol and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA). Leukemia 16 1331-1343... 

Gao N, Dai Y, Rahmani M et al. (2004) Contribution of disruption of the nuclear factor-kappaB pathway to induction of apoptosis in human leukemia cells by histone deacetylase inhibitors and flavopiridol. Mol Pharmacol 66 956-963... 

Yokoyama, Y, Kuramitsu, Y, Takashima, M., lizuka, N., Toda, T., Terai, S., Sakaida, L, Oka, M., Nakamura, K. and Okita, K., Proteomic profiling of proteins decreased in hepatocellular carcinoma from patients infected with hepatitis C virus. Proteomics, 4, 2111-2116 (2004). Parker, B.W., Kaur, G., Nieves-Neira, W., Taimi, M., Kohlhagen, G., Shimizu, T., Losiewicz, M.D., Pommier, Y, Sausville, E.A. and Senderowicz, A.M., Early induction of apoptosis in hematopoietic cell lines after exposure to flavopiridol. Blood, 91, 458-465 (1998). 

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