Effects of lysophosphatidic acid (LPA) signaling via LPA receptors on cellular functions associated with ATP reduction in osteosarcoma cells treated with ethidium bromide

• Published in: Journal of bioenergetics and biomembranes 2022-04, Vol.54 (2), p.109-117
• Main Authors: Kurisu, Rio, Takamoto, Miyu, Minami, Kanako, Ueda, Nanami, Yamada, Marina, Shima, Nanami, Otani, Tomoka, Sakai, Yuma, Kondo, Daisuke, Tsujiuchi, Toshifumi
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - pharmacology; Animal Anatomy; Animal Biochemistry; Apoptosis; ATP; Biochemistry; Biomedical materials; Bioorganic Chemistry; Bone cancer; Bone Neoplasms - drug therapy; Bone Neoplasms - genetics; Cancer; Cell Movement; Cell survival; Chemistry; Chemistry and Materials Science; Cisplatin; Depletion; Ethidium - pharmacology; Ethidium bromide; Gene Expression Regulation, Neoplastic; Histology; Humans; Intracellular; Invasiveness; Lysophosphatidic acid; Lysophospholipids - metabolism; Morphology; Necrosis; Organic Chemistry; Osteosarcoma; Osteosarcoma - drug therapy; Osteosarcoma - genetics; Osteosarcoma cells; Receptor mechanisms; Receptors; Receptors, Lysophosphatidic Acid - genetics; Receptors, Lysophosphatidic Acid - metabolism; Reduction; Sarcoma; Signaling; Survival
• ISSN: 0145-479X; 1573-6881
• DOI: 10.1007/s10863-022-09933-8

Lysophosphatidic acid (LPA) signaling via LPA receptors (LPA 1 to LPA 6 ) exhibits a variety of malignant properties in cancer cells. Intracellular ATP depletion leads to the development of necrosis and apoptosis. The present study aimed to evaluate the effects of LPA receptor-mediated signaling on the regulation of cancer cell functions associated with ATP reduction. Long-term ethidium bromide (EtBr) treated (MG63-EtBr) cells were established from osteosarcoma MG-63 cells. The intracellular ATP levels of MG63-EtBr cells were significantly lower than that of MG-63 cells. LPAR2 , LPAR3 , LPAR4 and LPAR6 gene expressions were elevated in MG63-EtBr cells. The cell motile and invasive activities of MG63-EtBr cells were markedly higher than those of MG-63 cells. The cell motile activity of MG-63 cells was increased by LPA 4 and LPA 6 knockdowns. In cell survival assay, cells were treated with cisplatin (CDDP) every 24 h for 3 days. The cell survival to CDDP of MG63-EtBr cells was lower than that of MG-63 cells. LPA 2 knockdown decreased the cell survival to CDDP of MG-63 cells. The cell survival to CDDP of MG-63 cells was inhibited by (2 S)-OMPT (LPA 3 agonist). Moreover, the cell survival to CDDP of MG-63 cells was enhanced by LPA 4 and LPA 6 knockdowns. These results indicate that LPA signaling via LPA receptors is involved in the regulation of cellular functions associated with ATP reduction in MG-63 cells treated with EtBr.