Onoseriolide, from Hedyosmum racemosum, induces cytotoxicity and apoptosis in human colon cancer cells Luis Miguel Guamán-Ortiz a , Natalia Bailón-Moscoso a , Vladimir Morocho b , Daisy Vega-Ojeda a , Fernando Gordillo b , Alírica I. Suárez b,c a Department, University, City, Country a Departamento de Ciencias de la Salud, Universidad Técnica Particular de Loja, 1101608. Loja, Ecuador. b Departamento de Química y Ciencias Exactas, Universidad Técnica Particular de Loja, 1101608. Loja, Ecuador. c Facultad de Farmacia, Universidad Central de Venezuela, 1050. Caracas, Venezuela. Corresponding author: Luis Miguel Guamán-Ortiz, Departamento de Ciencias de la Salud, Universidad Técnica Particular de Loja, San Cayetano Alto s/n, 1101608. Loja, Ecuador. Tel.: +593 07 3701444. E-mail: lmguaman@utpl.edu.ec . The number of colon cancer patients is increasing, and new alternatives for treatment are important. We focused on the sesquiterpene lactone onoseriolide from Hedyosmum racemosum, which is widely used in traditional medicine. This compound was evaluated to determine its cytotoxic effect and the mechanism of cell death that is induced in the human colon cancer cell line RKO. A dose- dependent decrease in cell viability was observed. p53 expression increased followed by an increase in p21 expression, which is involved in cell cycle arrest in the G 2 /M phase. Caspase-3 activation and PARP-1 cleavage, which are apoptotic markers, were also monitored. Autophagy markers were also studied, and Beclin 1 was downregulated, while LC-3II increased in a dose-dependent manner. There were no changes in SQSTM1/p62 regulation. Onoseriolide exerts cytotoxic and cytostatic effects, activating the autophagy pathway as a protective mechanism and apoptosis as the cell death pathway. Keywords: Hedyosmum racemosum; onoseriolide; colon cancer; cytotoxicity; apoptosis; autophagy