Anticancer Activity of Liposomes Prepared Solely From Cardiolipin
Arisa Sakamoto, Ippei Noboruo, Hiroshi Tateishi, Sho Tomita, Tomoki Fukuda, Kazumi Matsushima‐Nagata, Manabu Aoki, Daichi Kusakari, Takuya Masunaga, Nao Nishimura, Takaaki Ito, Masami Otsuka, Mikako Fujita, Kensaku AnrakuABSTRACT
Despite notable medical advancements, the continuous development of novel cancer therapies remains imperative. In this study, we aimed to evaluate the anticancer activity of liposomes prepared solely from nonnatural myristoylated (saturated C 14 chains) or natural cardiolipin to develop a cancer therapies strategy. We calculated IC 50 values using a cell proliferation inhibition assay and investigated the underlying mechanisms in cells exhibiting high inhibitory activity using Western blotting and flow cytometry. Calculation of the IC 50 revealed that liposomes prepared solely with natural cardiolipin exhibited low toxicity to normal cells (> 100 μM) and showed the strongest toxicity against cancer cells, specifically KMS‐12‐PE (multiple myeloma cells) (23.5 ± 11.4 μM) among various cancer cells. In contrast, liposomes prepared solely with myristoylated cardiolipin exhibited weak anticancer activity. Furthermore, the mechanism of anticancer activity was evaluated using immunoblotting and flow cytometry. After administration of natural cardiolipin liposomes, CASPASE‐3 cleavage was confirmed in KMS‐12‐PE cells, and the annexin V‐positive rate was higher than in the liposome‐free control group, suggesting apoptosis induction. These results indicate that natural cardiolipin is nontoxic to normal cells and possesses anticancer activity. This study demonstrated that liposomes formulated with cardiolipin can induce anticancer activity independently. This new finding is considered a foundation for future therapeutic strategies.