C-Phycocyanin Suppresses the In Vitro Proliferation and Migration of Non-Small-Cell Lung Cancer Cells through Reduction of RIPK1/NF-κB Activity

Abstract

Phycocyanin, derived from Spirulina platensis, is a type of natural antineoplastic marine protein. It is known that phycocyanin exerts anticancer effects on non-small-cell lung cancer (NSCLC) cells, but its underlying mechanism has not been elucidated. Herein, the antitumor function and regulatory mechanism of phycocyanin were investigated in three NSCLC cell lines for the first time: H358, H1650, and LTEP-a2. Cell phenotype experiments suggested that phycocyanin could suppress the survival rate, proliferation, colony formation, and migration abilities, as well as induce apoptosis of NSCLC cells. Subsequently, transcriptome analysis revealed that receptor-interacting serine/threonine-protein kinase 1 (RIPK1) was significantly down-regulated by phycocyanin in the LTEP-a2 cell, which was further validated by qRT-PCR and Western blot analysis in two other cell lines. Interestingly, similar to phycocyanin-treated assays, siRNA knockdown of RIPK1 expression also resulted in growth and migration inhibition of NSCLC cells. Moreover, the activity of NF-κB signaling was also suppressed after silencing RIPK1 expression, indicating that phycocyanin exerted anti-proliferative and anti-migratory function through down-regulating RIPK1/NF-κB activity in NSCLC cells. This study proposes a mechanism of action for phycocyanin involving both NSCLC apoptosis and down regulation of NSCLC genes.

Phycocyanin from Arthrospira platensis as Potential Anti-Cancer Drug: Review of In Vitro and In Vivo Studies

“…Recent anti-cancer studies of PC revealed a significant inhibitory effect on the growth of cancer cells in a time- and dose-dependent manner. Multiple mechanisms have been found, including the induction of apoptosis, cell cycle arrest, inhibition of DNA replication and the generation of reactive oxygen species (ROS) [ 32 , 36 , 37 , 38 ]. While apoptosis was significantly increased in cancerous cells, PC had a considerably lower toxicity on cells from healthy tissues, which makes it an appropriate candidate for chemotherapeutic applications [ 35 , 39 , 40 ].…”

Insulin Receptor Substrate 1 Is Involved in the Phycocyanin-Mediated Antineoplastic Function of Non-Small Cell Lung Cancer Cells

“…A large number of studies have shown that phycocyanin can inhibit the proliferation, cause cell cycle arrest and induce apoptosis of NSCLC cells [ 34 , 35 ]. Previously, our team had discovered that phycocyanin exerted anti-proliferative functions through reducing receptor-interacting serine/threonine-protein kinase 1 (RIPK1) and toll/interleukin 1 receptor domain-containing adaptor (TIRAP), two mediated proteins in multiple NSCLC cells, revealing the potential anticancer mechanism of phycocyanin in NSCLC [ 36 , 37 ]. Here, IRS-1, a key regulatory protein of phycocyanin, was investigated to participate in the growth and migration processes of NSCLC cells.…”

A highly purified C-phycocyanin from thermophilic cyanobacterium Thermosynechococcus elongatus and its cytotoxic activity assessment using an in vitro cell-based approach

“…This might be attributed to the fact that chemotherapeutic drugs employed for treatment of cancer are associated with several adverse side effects and short effective halflives in vivo. Indeed, natural products isolated from cyanobacteria are known for their potent anti-cancer activity [10,12,36]. Phycocyanin is a natural biologically active agent that is isolated and purified from various microalgae and seaweeds [37].…”

“…Several studies have pointed to the role of C-PC as an antioxidant, anti-cancer, neuroprotective, immunomodulatory, anti-inflammatory agent, as well as a non-toxic photosensitizer in tumour treatment [5][6][7]. The importance of pure C-PC resides in its anti-proliferative and pro-apoptotic effects on different types of cancer cell lines [8][9][10][11], where there are no recorded side effects on normal cells [5,12]. For this reason, the purity of C-PC is considered the main challenge among researchers [3,13].…”