Phycocyanin Exerts Anti-Proliferative Effects through Down-Regulating TIRAP/NF-κB Activity in Human Non-Small Cell Lung Cancer Cells

Abstract

Phycocyanin is a type of marine functional food additive, exerting a health care efficacy with no side effects. It has been shown that phycocyanin possesses anticancer function in non-small cell lung cancer (NSCLC) cells, but the underlying regulatory mechanism still remains unclear. Further investigation on the antineoplastic mechanism of phycocyanin would provide useful information on NSCLC treatment. In this study, we explored the in vitro function and mechanism of phycocyanin in three typical NSCLC cell lines, H1975, H1650, and LTEP-a2, for the first time. Phenotypic experiments showed that phycocyanin significantly induced the apoptosis as well as suppressed the growth of NSCLC cells. Transcriptome analysis suggested that toll/interleukin 1 receptor domain-containing adaptor protein (TIRAP) was significantly down-regulated by phycocyanin. Strikingly, similar to phycocyanin-treated assays, siRNA knockdown of TIRAP expression also resulted in the anti-proliferative phenomenon in NSCLC cells. In addition, the activity of NF-κB signaling was also suppressed after silencing TIRAP expression, revealing that phycocyanin exerted anti-proliferative function through down-regulating TIRAP/NF-κB activity in NSCLC cells. Collectively, this study has laid a theoretical basis on the treatment of NSCLC and the potential utilization of marine functional products.

Paradoxical Roles of the MAL/Tirap Adaptor in Pathologies

“…In the emerging field of host-directed therapies to intracellular pathogens, TLRs and their adaptor proteins were proposed as putative targets for the treatment of inflammatory disorders and to overcome microbial resistance ( 76 ). For example, Gefitinib, Phycocianin and other peptides were recently studied for their inhibiting effect on MAL in the context of endotoxic injury, lung cancers and autoimmune diseases, respectively, showing promising results ( 77 – 80 ).…”

Isolation of Industrial Important Bioactive Compounds from Microalgae

“…has also been reported ( Table 1 ) [ 38 , 40 ]. C-phycocyanin showed inhibitory activity in liver cancer cell lines (HepG2) [ 34 ], human leukemia cells (K562) [ 35 ] and against lung cancer cell lines (A549 and NSCLC) [ 36 , 37 , 38 ]. In another study, the phycocyanin from Limnothrix sp.…”

<p>Exploring DNA Methylation Profiles Altered in Cryptogenic Hepatocellular Carcinomas by High-Throughput Targeted DNA Methylation Sequencing: A Preliminary Study for Cryptogenic Hepatocellular Carcinoma</p>

“…30,31 In NSCLC cells, knockdown of TIRAP expression by siRNA suppressed proliferation. 32 Cortactin (CTTN) has been identified as a biomarker of cancer metastasis due to its overexpression in various cancers, such as colorectal cancer, head and neck squamous cell carcinoma, among others. Results have suggested that CTTN inhibits the degradation of EGF and promotes the proliferation of CRC cells.…”