Piplartine induces inhibition of leukemia cell proliferation triggering both apoptosis and necrosis pathways Daniel Pereira Bezerraa, Gardenia Carmen Gadelha Militãoa, Fernanda Oliveira de Castroa, Cláudia Pessoaa, Manoel Odorico de Moraesa, Edilberto Rocha Silveirab, Mary Anne Sousa Limab, Francisca Juliana Martins Elmirob and Letícia Veras Costa-Lotufoa, aDepartamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Caixa Postal 3157, 60430-270 Fortaleza, Ceará, Brazil bDepartamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Caixa Postal 12200, 60021-940 Fortaleza, Ceará, Brazil Received 13 May 2006; accepted 6 July 2006. Available online 28 July 2006. Abstract Piplartine {5,6-dihydro-1-[1-oxo-3-(3,4,5-trimethoxyphenyl)-2-propenyl]-2(1H)pyridinone} is an alkaloid/amide component of Piper species. The purpose of the present study was to examine the antiproliferative effects of piplartine on human leukemia cell lines HL-60, K562, Jukart, and Molt-4 using the trypan blue exclusion method, as well as the effect of piplartine on DNA synthesis. The viability of all human leukemia cell lines were not affected by piplartine after 6 h, 9 h, and 12 h exposure, whereas a steady decline was seen after an exposure time of 24 h. The antiproliferative activity of piplartine seemed to be related to the inhibition of DNA synthesis, as revealed by the reduction of 5-bromo-2’-deoxyuridine (BrdU) incorporation after 24 h of incubation. Piplartine-mediated reduction in cell number was associated with an increasing number of dead cells at a concentration of 10 μg/ml. These findings were corroborated by morphologic analysis. However, at the lowest concentration (2.5 μg/ml), piplartine-treated cells exhibited typical apoptotic morphological changes. The increase in caspase-3 activity was also observed in lysates of piplartine-treated cells (2.5 μg/ml). Our findings suggest that piplartine can suppress leukemia growth and reduce cell survival, triggering both apoptosis and/or necrosis, depending on the concentration used. Toxicology in Vitro Volume 21, Issue 1 , February 2007, Pages 1-8 doi:10.1016/j.tiv.2006.07.007 From a Tulane University paper (2000): "Piper cenocladum C. DC. is an understory shrub (usually less than 4 metres tall) common in wet forests throughout the Atlantic lowlands of Costa Rica. Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.