College of Life Science, Chongqing Normal University, Chongqing, 401331, China.
School of Education, Chongqing Normal University, Chongqing, 401331, China.
Med Oncol. 2022 Jun 6;39(8):112. doi: 10.1007/s12032-022-01729-5.
Snake venom L-Amino-acid oxidase (svLAAO) has become a critical research target in molecular biology and medical science since its widespread presence and diverse biological roles, including antitumor application. Our research confirmed that Crotalus adamanteus (C. adamanteus) venom LAAO exhibited potential anti-ovarian cancer activity both in vivo and in vitro. C. adamanteus venom LAAO significantly reduced viability of ovarian cancer cells and caused morphological changes that preceded cell death. The results of molecular biology experiments showed that C. adamanteus venom LAAO caused expression changes of genes related to apoptotic pathways either intrinsically or extrinsically in ovarian cancer cells. Animal experiments and histological analysis also proved that C. adamanteus venom LAAO could effectively inhibit the tissue damage caused by ovarian cancer, and animals treated with C. adamanteus venom LAAO showed higher survival time. Catalase blocked the major apoptosis induction of C. adamanteus venom LAAO on ovarian cancer cells, suggesting that the cytotoxicity of C. adamanteus venom LAAO on ovarian cancer cells was mainly mediated by HO. These results infer that C. adamanteus venom LAAO will have some advantages in new drug research and antitumor drug development in future.
蛇毒 L-氨基酸氧化酶(svLAAO)因其广泛存在和多种生物学作用,包括抗肿瘤应用,已成为分子生物学和医学科学的重要研究目标。我们的研究证实,响尾蛇(C. adamanteus)毒液 LAAO 在体内和体外均表现出潜在的抗卵巢癌活性。响尾蛇毒液 LAAO 显著降低了卵巢癌细胞的活力,并导致细胞死亡前的形态变化。分子生物学实验的结果表明,响尾蛇毒液 LAAO 导致卵巢癌细胞内在或外在的凋亡途径相关基因表达发生变化。动物实验和组织学分析也证明,响尾蛇毒液 LAAO 能有效抑制卵巢癌引起的组织损伤,用响尾蛇毒液 LAAO 治疗的动物表现出更高的存活时间。过氧化氢酶阻断了响尾蛇毒液 LAAO 对卵巢癌细胞的主要凋亡诱导作用,表明响尾蛇毒液 LAAO 对卵巢癌细胞的细胞毒性主要是通过 HO 介导的。这些结果推断,响尾蛇毒液 LAAO 在未来的新药研究和抗肿瘤药物开发中将具有一些优势。