Laboratory of Histochemistry and Functional Morphology, Institute of Biochemistry after H. Buniatian, NAS RA, 0014 Yerevan, Republic of Armenia.
Department of Genetics and Cytology, Faculty of Biology, Yerevan State University, 0025 Yerevan, Republic of Armenia.
Oncol Rep. 2020 Jul;44(1):196-212. doi: 10.3892/or.2020.7604. Epub 2020 May 4.
A new type of bioactive polypeptides of the neurosecretory hypothalamus called proline‑rich peptides (PRPs), which are isolated from bovine neurosecretory granules of the neurohypophysis, are synthesized in the form of a common precursor protein (neurophysin vasopressin‑associated glycoprotein). Proline‑rich polypetide 1 (PRP‑1; also known as galarmin) is comprised of 15 amino acids residues, and has been suggested to possess anti‑neurodegenerative, immunoregulatory, hematopoietic, antimicrobial and antitumor properties. The cytostatic, antiproliferative effect of PRP‑1 was demonstrated in the human chondrosarcoma JJ012 and triple negative breast carcinoma MDA MB 231 cell lines. PRP‑1 action is disease and tissue specific. To further explore the antitumorigenic and possible cytotoxic effects of PRP‑1, a morpho‑functional study on the effect of PRP‑1 on a mouse Ehrlich ascites carcinoma (EAC) model was conducted. The PRP‑1‑induced morphological features of EAC cells confirmed the apoptotic nature of PRP‑1, as manifested by cell shrinkage, membrane blebbing, chromosome condensation (pyknosis) and nuclear fragmentation (karyorrhexis). The effect of PRP‑1 on the number of tumor cells incubated for 24 h and their viability in trypan blue‑stained samples lead to a 44% reduction in the number of viable cells on day 11 post‑inoculation vs. 22% inhibition of viable cells after PRP‑1 treatment (0.1 µg/ml) on day 7 post‑inoculation. Apoptosis experiments using an Annexin V‑cyanine 3 apoptosis detection kit indicated that 24 h incubation with 0.1 µg/ml PRP‑1 caused a significant increase in the number of apoptotic cells, reaching 50.33%, compared to 8.33% in the sample control on day 7 post‑inoculation.
一种新型的神经分泌下丘脑的生物活性多肽,称为脯氨酸丰富肽(PRPs),它是从牛神经垂体的神经分泌颗粒中分离出来的,是以一种共同的前体蛋白(神经垂体加压素相关糖蛋白)的形式合成的。脯氨酸丰富多肽 1(PRP-1;也称为 galarmin)由 15 个氨基酸残基组成,被认为具有抗神经退行性、免疫调节、造血、抗菌和抗肿瘤特性。PRP-1 在人软骨肉瘤 JJ012 和三阴性乳腺癌 MDA MB 231 细胞系中表现出细胞抑制、抗增殖作用。PRP-1 的作用是疾病和组织特异性的。为了进一步探索 PRP-1 的抗肿瘤和可能的细胞毒性作用,对 PRP-1 对小鼠艾氏腹水癌(EAC)模型的形态功能进行了研究。PRP-1 诱导的 EAC 细胞形态特征证实了 PRP-1 的凋亡性质,表现为细胞收缩、细胞膜起泡、染色体浓缩(固缩)和核碎裂(核碎裂)。PRP-1 对孵育 24 小时的肿瘤细胞数量及其在台盼蓝染色样本中的活力的影响导致接种后第 11 天活细胞数量减少 44%,而接种后第 7 天 PRP-1 处理(0.1μg/ml)后活细胞抑制率为 22%。使用 Annexin V-氰基 3 凋亡检测试剂盒进行的凋亡实验表明,24 小时孵育 0.1μg/ml PRP-1 导致凋亡细胞数量显著增加,达到 50.33%,而接种后第 7 天样品对照为 8.33%。