Li Chuan, Imai Masahiko, Yamasaki Masahiro, Hasegawa Shinya, Takahashi Noriko
Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University.
Biol Pharm Bull. 2017 Apr 1;40(4):486-494. doi: 10.1248/bpb.b16-00933. Epub 2017 Jan 18.
Vitamin A is an essential nutrient that is obtained from the daily diet. The major forms of vitamin A in the body consist of retinol, retinal, retinoic acid (RA), and retinyl esters. Retinal is fundamental for vision and RA is used in clinical therapy of human acute promyelocytic leukemia. The actions of retinol and retinyl palmitate (RP) are not known well. Recently, we found that retinol is a potent anti-proliferative agent against human refractory cancers, including gallbladder cancer, being more effective than RA, while RP was inactive. In the current study, we determined serum retinol concentrations in xenograft mice bearing tumors derived from four refractory cancer cell lines. We also examined the effects of vitamin A on proliferation of human gallbladder cancer cells in vivo. Serum retinol concentrations were significantly lower in xenograft mice with tumors derived from various refractory cancer cell lines as compared with control mice. The growth of tumors was inhibited with increasing serum retinol concentrations obtained post-administration of RP. In addition, pre-administration of RP increased serum retinol concentrations and suppressed tumor growth. These results indicate that administration of RP can maintain retinol concentrations in the body and that this might suppress cancer cell growth and attachment. The regulation of vitamin A concentration in the body, which is critical biomarker of health, could be beneficial for cancer prevention and therapy.
维生素A是一种从日常饮食中获取的必需营养素。体内维生素A的主要形式包括视黄醇、视黄醛、维甲酸（RA）和视黄酯。视黄醛对视力至关重要，维甲酸用于人类急性早幼粒细胞白血病的临床治疗。视黄醇和棕榈酸视黄酯（RP）的作用尚不清楚。最近，我们发现视黄醇是一种针对包括胆囊癌在内的人类难治性癌症的有效抗增殖剂，比维甲酸更有效，而棕榈酸视黄酯则无活性。在本研究中，我们测定了携带源自四种难治性癌细胞系肿瘤的异种移植小鼠的血清视黄醇浓度。我们还研究了维生素A对体内人胆囊癌细胞增殖的影响。与对照小鼠相比，源自各种难治性癌细胞系肿瘤的异种移植小鼠的血清视黄醇浓度显著降低。随着棕榈酸视黄酯给药后血清视黄醇浓度的增加，肿瘤生长受到抑制。此外，预先给予棕榈酸视黄酯可提高血清视黄醇浓度并抑制肿瘤生长。这些结果表明，给予棕榈酸视黄酯可以维持体内视黄醇浓度，这可能会抑制癌细胞的生长和附着。体内维生素A浓度的调节是健康的关键生物标志物，可能对癌症预防和治疗有益。
