Abstract
Polygonatum odoratum lectin (POL), isolated from traditional Chinese medicine herb (Mill.) Druce, has drawn rising attention due to its wide biological activities. In the present study, anti-tumor effects, including apoptosis- and autophagy-inducing properties of POL, were determined by a series of cell biology methods such as MTT, cellular morphology observation, flow cytometry, immunoblotting. Herein, we found that POL could simultaneously induce apoptosis and autophagy in human non-small cell lung cancer A549 cells. POL initiated apoptosis through inhibiting Akt-NF-κB pathway, while POL triggered autophagy via suppressing Akt-mTOR pathway, suggesting the molecular switch role of Akt in regulating between POL-induced apoptosis and autophagy. Moreover, ROS was involved in POL-induced inhibition of Akt expression, and might therefore mediate both apoptosis and autophagy in A549 cells. In addition, POL displayed no significant cytotoxicity toward normal human embryonic lung fibroblast HELF cells. Due to the anti-tumor activities, POL might become a potent anti-cancer drug in future therapy, which might pave the way for exploring GNA-related lectins into effective drugs in cancer treatment.
Highlights
Lectins are designated as carbohydrate-binding proteins that widely exist in animals, plants and microorganisms, and they could bind carbohydrates, agglutinate cells or precipitate polysaccharides and glycoconjugates [1]
Assay on human cancer cells, including colon carcinoma Caco-2 cells, cervix carcinoma HeLa cells, non-small cell lung cancer A549 cells, hepatocellular carcinoma HepG2 and 7721 cells, breast carcinoma MCF-7 cells, melanoma A375 cells, and the IC50 values were 47 mg/mL, 30 mg/mL, 23 mg/mL, 42 mg/mL, 38 mg/mL, 50 mg/mL and 26 mg/mL, respectively (Fig. 1B). This result showed that Polygonatum odoratum lectin (POL) was more sensitive to non-small cell lung cancer A549 cells, and A549 cells were chosen for further exploration
POL bears different anti-neoplastic effects toward different cancer cells, of which POL was more sensitive to non-small cell lung cancer A549 cells with IC50 value at 23 mg/mL (24 h)
Summary
Lectins are designated as carbohydrate-binding proteins that widely exist in animals, plants and microorganisms, and they could bind carbohydrates, agglutinate cells or precipitate polysaccharides and glycoconjugates [1]. Cancer is associated with programmed cell death (PCD), which plays important roles in homeostasis preservation, cellular differentiation, growth control, cell defense and etc., jointly sealing the ultimate fate of cancer cells [5]. There are two main types of PCD, referring to apoptosis and autophagy. Autophagy is an evolutionarily conserved cellular mechanism for clearance of damaged or superfluous macro-complexes and organelles in eukaryotic cells, which leads to either pro-survival or pro-death effects [6]. Autophagy and apoptosis bear distinct morphological characteristics and physiological process, there still exist intricate interrelationships between them [7]
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