Gamma‐linolenic acid induces apoptosis and lipid peroxidation in human chronic myelogenous leukemia K562 cells

Abstract

Various polyunsaturated fatty acids, especially gamma-linolenic acid (GLA), inhibit the growth of a variety of tumor cells. Some evidence indicates that polyunsaturated fatty acid can kill cells by apoptosis. In the current study, we tested the apoptotic effect of GLA on human chronic myelogenous leukemia K562 cells. GLA induced K562 cell death in a dose-dependent manner. Typical apoptotic nuclei were shown by staining of K562 cells with DNA-binding fluorochrome Hoechst 33342, characterized by chromatin condensation and nuclear fragmentation. Flow cytometric analysis also demonstrated that GLA caused dose-dependent apoptosis of K562 cells. The apoptosis could be inhibited by a pancaspase inhibitor (z-VAD-fmk), suggesting the involvement of caspases. Further, release of cytochrome c, activation of caspase-3 and cleavage of PARP were found in GLA-induced apoptosis. GLA treatment could also elevate lipid peroxidation in K562 cells, and antioxidant alpha-tocopherol could reverse the cytotoxicity of GLA. The saturated fatty acid SA, which did not exhibit significant increase in lipid peroxidation, also did not induce cytotoxicity. Intracellular GSH was also determined, and there was no marked change of GSH levels in cells after incubation with GLA compared with the control. These results demonstrate that GLA could induce apoptosis in K562 cells. Apoptosis is mediated by release of cytochrome c, activation of caspase-3. Lipid peroxidation may play a role in GLA cytotoxicity.

Multiple roles of dihomo-γ-linolenic acid against proliferation diseases

“…This implies that an interaction exists among fatty acids, lipid peroxidation process, apoptosis and genes/oncogenes that regulate apoptotic process [6-10]. Researches previously have showed that some polyunsaturated fatty acids (PUFAs) induced apoptosis of tumor cells with little or no cytotoxic action on normal cells under certain conditions [6,68,69]. It was observed that of all the fatty acids tested, GLA or DGLA was the most effective in selectively killing the tumor cells [6].…”

“…It was observed that of all the fatty acids tested, GLA or DGLA was the most effective in selectively killing the tumor cells [6]. In a co-culture experiment wherein normal human skin fibroblasts and human breast cancer cells were grown together in a petri dish supplemented with GLA or DGLA, only human breast cancer cells were eliminated without any effect on normal skin fibroblasts [65,68,70,71]. These results reconfirmed that GLA or DGLA show selective tumoricidal action at least in vitro.…”

Cytotoxic effects of the compound cis-tetraammine(oxalato)ruthenium(III) dithionate on K-562 human chronic myelogenous leukemia cells

“…Chemotherapy is a common treatment for leukemia (Ge et al 2009). In general the therapy uses a number of different anticancer drugs, which destroy cancer cells by preventing them from growing and dividing rapidly.…”

“…In general the therapy uses a number of different anticancer drugs, which destroy cancer cells by preventing them from growing and dividing rapidly. Unfortunately, a number of the body’s normal, non-cancerous cells (e.g., hair cells, red and white blood cells, blood-clotting platelets, and cells of the gastrointestinal mucosa) also divide rapidly and are harmed by chemotherapy (Ge et al 2009; Kim et al 2002). The side effects of chemotherapy hamper many normal activities of patients undergoing treatment (Kim et al 2002).…”

Efficiency of Borage Seeds Oil Against Gamma Irradiation-Induced Hepatotoxicity in Male Rats: Possible Antioxidant Activity

“…Several classes of these components act as antioxidants (Shahidi and Shukla, 1996). Borage seeds oil is the richest plant source of -linolenic acid (GLA) which is used as dietary supplement for prevention and/or treatment of various degenerative pathologies illnesses (Asadi-Samani et al, 2014), as osteoporosis (Kruger et al, 1998), diabetes (Das, 2010), and cancer (Ge et al, 2009 ;Itoh et al, 2010). GLA has also been reported to suppress tumor growth in vitro (Pham et al, 2006), improve oxygenation status (Mancuso et al, 1997), exert anti-inflammatory activity and display beneficial effects in the early stages of sepsis (Horrobin, 1992; Pontes-Arruda et al, 2011).…”