Trans‐10,cis‐12 CLA suppresses osteosarcoma cells via phosphoinositide 3‐kinase pathway

Abstract

Cancer is one of the leading causes of death in the United States, second only to the heart disease. Osteosarcoma is one of the most common and aggressive types of cancer in adolescents and children. Conjugated linoleic acid (CLA), cis‐9,trans‐11 and trans‐10,cis‐12, have shown isomer dependent anticancer properties in in vitro and in vivo studies. Previously, CLA, particularly the trans‐10,cis‐12 isomer, was shown to reduce tumor development and apoptosis in a canine osteosarcoma model, CCL‐183, via non‐steroidal anti‐inflammatory drug‐activated gene 1 (NAG‐1). Thus, the purpose of the current investigation was to determine the specific apoptotic pathway induced by NAG‐1 mediated effects of the trans‐10, cis‐12 CLA isomer. Major cell proliferation protein enzymes, phosphoinositide 3‐kinases (PI3K), c‐Jun N‐terminal kinases (JNKs), Protein kinase C (PKC), and extracellular signal‐regulated kinases/MAP kinase (ERK/MAPs), all of which act as control point(s) of extrinsic apoptosis pathway, were tested. The trans‐10,cis‐12 CLA isomer effectively suppressed the tumor cell growth after 72 hour treatment via phosphoinositide 3‐kinase (PI3K), which was associated with the expression of NAG‐1. Neither apoptotic effect nor NAG‐1 expression were found in the other three kinases or other fatty acids tested. These results confirm that anticancer effects of the trans‐10,cis‐12 CLA isomer on osteosarcomas are via a PI‐3 kinase pathway.