Centro Multidisciplinario de Estudios en Biotecnología-FMVZ, Universidad Michoacana de San Nicolás de Hidalgo, Posta Veterinaria, Morelia 58893, Mexico.
Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Morelia 58030, Mexico.
Molecules. 2021 Jul 9;26(14):4178. doi: 10.3390/molecules26144178.
Osteosarcoma is the most common malignant bone tumor in both children and dogs. It is an aggressive and metastatic cancer with a poor prognosis for long-term survival. The search for new anti-cancer drugs with fewer side effects has become an essential goal for cancer chemotherapy; in this sense, the bioactive compounds from avocado have proved their efficacy as cytotoxic molecules. The objective of this study was to determine the cytotoxic and antiproliferative effect of a lipid-rich extract (LEAS) from Mexican native avocado seed ( var. drymifolia) on canine osteosarcoma D-17 cell line. Also, the combined activity with cytostatic drugs was evaluated. LEAS was cytotoxic to D-17 cells in a concentration-dependent manner with an IC = 15.5 µg/mL. Besides, LEAS induced caspase-dependent cell apoptosis by the extrinsic and intrinsic pathways. Moreover, LEAS induced a significant loss of mitochondrial membrane potential and increased superoxide anion production and mitochondrial ROS. Also, LEAS induced the arrest of the cell cycle in the G0/G1 phase. Finally, LEAS improved the cytotoxic activity of cisplatin, carboplatin, and in less extension, doxorubicin against the canine osteosarcoma cell line through a synergistic effect. In conclusion, avocado could be a potential source of bioactive molecules in the searching treatments for osteosarcoma.
骨肉瘤是儿童和犬类中最常见的恶性骨肿瘤。它是一种侵袭性和转移性癌症，长期生存的预后较差。寻找副作用更少的新抗癌药物已成为癌症化疗的重要目标；在这方面，鳄梨的生物活性化合物已被证明是细胞毒性分子的功效。本研究的目的是确定来自墨西哥本地鳄梨种子（var. drymifolia）的富含脂质的提取物（LEAS）对犬骨肉瘤 D-17 细胞系的细胞毒性和抗增殖作用。此外，还评估了与细胞抑制剂联合的活性。LEAS 以浓度依赖性方式对 D-17 细胞具有细胞毒性，IC = 15.5 µg/mL。此外，LEAS 通过外在和内在途径诱导 caspase 依赖性细胞凋亡。此外，LEAS 诱导线粒体膜电位显著丧失，并增加超氧阴离子产生和线粒体 ROS。此外，LEAS 诱导细胞周期停滞在 G0/G1 期。最后，LEAS 通过协同作用提高了顺铂、卡铂和在较小程度上阿霉素对犬骨肉瘤细胞系的细胞毒性活性。总之，鳄梨可能是寻找骨肉瘤治疗方法的生物活性分子的潜在来源。
