Up-regulation of MMP-2 and MMP-9 plays a significant role in promoting cancer progression by degrading the components of the extracellular matrix, thereby enhancing the migration of tumor cells. Although the anti-proliferative and apoptotic effect of Annona muricata is well established, its effect on MMP-2 and MMP-9, a major target in several types of cancers, has not been studied. Powdered samples of various parts of A. muricata like fruit, stem, seed, and twig extracted using aqueous methanol showed significant dose-dependent inhibition of MMP-2 and MMP-9 in a highly metastatic fibrosarcoma cell line, HT1080. Additionally, these extracts also up-regulated the expression of several endogenous inhibitors of MMP-2 and MMP-9 like REversion-inducing Cysteine-rich protein with Kazal motifs (RECK) and Tissue Inhibitor of Metalloproteinase-2 (TIMP-2). Furthermore, primary cells developed from tumor tissues obtained from patients not exposed to chemotherapy, also exhibited similar results. Remarkably, the inhibition of MMP-2 and MMP-9 observed was tumor specific, with the A. muricata fruit extract showing only 2% inhibition in cells obtained from normal tissues, when compared to 60% inhibition observed in cells obtained from tumor samples. The present study elucidates a novel mechanism by which A. muricata extracts selectively exhibit their anti-cancer activity in tumor cells by down-regulating MMP-2 and MMP-9 that are important biomarkers in cancer.

中文翻译：

---

RECK和TIMP-2介导Annona muricata对MMP-2和MMP-9的抑制

MMP-2和MMP-9的上调通过降解细胞外基质的成分，从而增强肿瘤细胞的迁移，在促进癌症进展中起重要作用。尽管番荔枝的抗增殖和凋亡作用已得到充分证实，但尚未研究其对 MMP-2 和 MMP-9（几种类型癌症的主要靶点）的影响。使用甲醇水溶液提取的 A. muricata 各个部分（如果实、茎、种子和树枝）的粉末样品在高度转移性纤维肉瘤细胞系 HT1080 中显示出显着的剂量依赖性抑制 MMP-2 和 MMP-9。此外，这些提取物还上调了 MM​​P-2 和 MMP-9 的几种内源性抑制剂的表达，如具有 Kazal 基序的 REversion 诱导富含半胱氨酸蛋白 (RECK) 和金属蛋白酶组织抑制剂 2 (TIMP-2)。此外，从未接受化疗的患者获得的肿瘤组织中发育的原代细胞也表现出类似的结果。值得注意的是，观察到的 MMP-2 和 MMP-9 的抑制是肿瘤特异性的，与在从肿瘤样本获得的细胞中观察到的 60% 的抑制相比，从正常组织获得的细胞中，A. muricata 果实提取物仅显示 2% 的抑制。本研究阐明了一种新机制，通过该机制，A. muricata 提取物通过下调作为癌症中重要生物标志物的 MMP-2 和 MMP-9，选择性地在肿瘤细胞中表现出其抗癌活性。muricata 果实提取物在从正常组织获得的细胞中仅显示 2% 的抑制，而在从肿瘤样本获得的细胞中观察到的抑制为 60%。本研究阐明了一种新机制，通过该机制，A. muricata 提取物通过下调作为癌症中重要生物标志物的 MMP-2 和 MMP-9，选择性地在肿瘤细胞中表现出其抗癌活性。muricata 果实提取物在从正常组织获得的细胞中仅显示 2% 的抑制，而在从肿瘤样本获得的细胞中观察到的抑制为 60%。本研究阐明了一种新机制，通过该机制，A. muricata 提取物通过下调作为癌症中重要生物标志物的 MMP-2 和 MMP-9，选择性地在肿瘤细胞中表现出其抗癌活性。