Abstract
Lung cancer remains the leading cause of cancer death worldwide. Despite the recent advances in cancer treatment, only a subset of patients responds to targeted and immune therapies, and many patients developing resistance after an initial response. Lactoferrin (Lf) is a natural glycoprotein with immunomodulatory and anticancer activities. We produced a novel recombinant human Lf (rhLf) that exhibits glycosylation profile compatible with the natural hLf for potential parenteral therapeutic applications. The aim of this study was to evaluate the anticancer effects of this novel rhLf in human lung adenocarcinoma cells and its mechanisms of action. The results showed a concentration-dependent inhibition of A549 cancer cell growth in response to rhLf. Treatment with 1 mg/ml of rhLf for 24 h and 72 h resulted in a significant inhibition of cancer cell growth by 32% and 25%, respectively. Moreover, rhLf increased fourfold the percentage of early and late apoptotic cells compared to the control. This effect was accompanied by increased levels of caspase-3 activity and cell cycle arrest at the S phase in rhLf-treated cancer cells. Furthermore, rhLf significantly attenuated A549 cell migration. Importantly, treatment of normal human bronchial epithelial (NHBE) cells with rhLf showed the cell viability and morphology comparable to the control. In contrast, chemotherapeutic etoposide induced cytotoxicity in NHBE cells and reduced the cell viability by 40%. These results demonstrate the selective anticancer effects of rhLf against lung adenocarcinoma cells without cytotoxicity on normal human cells. This study highlights a potential for clinical utility of this novel rhLf in patients with lung cancer.
Highlights
Cancer is a growing public health issue and is still one of the greatest medical challenges worldwide (Bray et al 2018)
The results showed that recombinant human Lf (rhLf) induced a concentration-dependent inhibition of A549 cell growth after 24 h treatment (Fig. 1A) and this anticancer effect was observed for the 72 h (Fig. 1B)
Our study demonstrated that rhLf exhibits the anticancer effects in human lung adenocarcinoma cells and has no cytotoxic effect on normal human bronchial epithelial (NHBE) cells
Summary
Cancer is a growing public health issue and is still one of the greatest medical challenges worldwide (Bray et al 2018). Despite the recent major advances in cancer treatment by applying targeted and immune therapies, clinical studies have shown that only a subset of patients respond to checkpoint blockade treatment and targeted therapy has benefit for selected patients with specific molecular subtypes of lung cancer (Qiao et al 2018; Yoneda et al 2018). While the cytotoxicity of current chemotherapeutics is still a major clinical issue, a standard chemotherapy remains the most common treatment for lung cancer patients (Carbone et al 2015). There is an urgent need to develop alternative therapeutics that would discriminate the cytotoxic effects between cancer and normal cells to minimize adverse events and improve clinical outcome. Research on the development of novel, non-toxic therapeutics has been one of the most actively pursued priorities in this area (Guedes et al 2018)
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