Díaz-Betancourt Andrea, Galicia-Castillo María Elizabeth, Morales-Tlalpan Verónica, Chávez-Servín Jorge Luis, Blanco-Labra Alejandro, García-Gasca Teresa, Saldaña Carlos
Laboratorio de Biofísica de Membranas y Nanotecnología, Facultad de Ciencias Naturales, Universidad Autonoma de Queretaro, Av. De las Ciencias s/n, Juriquilla, Queretaro 76230, Queretaro, Mexico.
Laboratorio Nacional de Visualización Científica Avanzada, Facultad de Ciencias Naturales, Universidad Autonoma de Queretaro, Av. De las Ciencias s/n, Juriquilla, Queretaro 76230, Queretaro, Mexico.
Int J Mol Sci. 2025 Jan 26;26(3):1064. doi: 10.3390/ijms26031064.
Lectins are proteins that specifically recognize carbohydrates on cell membranes, triggering several cellular events such as apoptosis of cancer-transformed cells; however, the mechanisms of action remain incompletely understood. Our research group has reported that a concentrated fraction of Tepary bean lectins (; TBLF) exhibits the concentration-dependent induction of apoptosis in colon cancer cells by caspase activation. It is well established that an increase in cytoplasmic calcium ([Ca]) initiates intracellular signals involved in processes such as exocytosis, gene transcription, apoptosis, cell cycle regulation, and muscle contraction, among others. Furthermore, dysregulated calcium signaling has been implicated in various diseases, including certain neurological disorders and cancer. In this study, we aim to demonstrate the effects of native TBLF lectins and a recombinant lectin (rTBL-1) on calcium mobility in breast cancer cells (MCF-7) and non-cancerous cells (MCF-12F). Both TBLF and rTBL-1 increased intracellular calcium concentrations and mobilized calcium from intracellular stores in a concentration-dependent manner; however, the two cell lines exhibited differential responses. While MCF-12F cells restored cytoplasmic calcium concentration, MCF-7 cells maintained a high intracellular calcium concentration. This strongly suggests that lectins can elicit differential cellular responses in cancer and non-cancer cells due to variations in their intrinsic mechanisms of calcium homeostasis. Finally, we demonstrated that TBLF and rTBL-1 can differentially alter Metabolic Cellular Activity (MCA) as a direct measure of cell viability (CVi) in both cell lines. These findings strengthen the evidence of the therapeutic potential of Tepary bean lectins. Undoubtedly, further studies will be necessary to elucidate the mechanisms underlying their applications.
凝集素是一类能特异性识别细胞膜上碳水化合物的蛋白质,可引发多种细胞事件,如癌症转化细胞的凋亡;然而,其作用机制仍未完全明确。我们的研究小组报告称, tepary豆凝集素的浓缩组分(TBLF)通过半胱天冬酶激活,呈现出对结肠癌细胞凋亡的浓度依赖性诱导作用。众所周知,细胞质钙([Ca])的增加会引发参与胞吐作用、基因转录、凋亡、细胞周期调控以及肌肉收缩等过程的细胞内信号。此外,钙信号失调与包括某些神经疾病和癌症在内的多种疾病有关。在本研究中,我们旨在证明天然TBLF凝集素和重组凝集素(rTBL-1)对乳腺癌细胞(MCF-7)和非癌细胞(MCF-12F)中钙流动性的影响。TBLF和rTBL-1均以浓度依赖性方式增加细胞内钙浓度并从细胞内储存库中动员钙;然而,这两种细胞系表现出不同的反应。MCF-12F细胞恢复了细胞质钙浓度,而MCF-7细胞维持了较高的细胞内钙浓度。这有力地表明,由于钙稳态内在机制的差异,凝集素可在癌细胞和非癌细胞中引发不同的细胞反应。最后,我们证明TBLF和rTBL-1可以不同程度地改变代谢细胞活性(MCA),以此作为两种细胞系中细胞活力(CVi)的直接指标。这些发现强化了tepary豆凝集素具有治疗潜力的证据。毫无疑问,需要进一步研究以阐明其应用背后的机制。