Phycocyanin Inhibits Tumorigenic Potential of Pancreatic Cancer Cells: Role of Apoptosis and Autophagy

Abstract

Pancreatic adenocarcinoma (PDA) is one of the most lethal human malignancies, and unresponsive to current chemotherapies. Here we investigate the therapeutic potential of phycocyanin as an anti-PDA agent in vivo and in vitro. Phycocyanin, a natural product purified from Spirulina, effectively inhibits the pancreatic cancer cell proliferation in vitro and xenograft tumor growth in vivo. Phycocyanin induces G2/M cell cycle arrest, apoptotic and autophagic cell death in PANC-1 cells. Inhibition of autophagy by targeting Beclin 1 using siRNA significantly suppresses cell growth inhibition and death induced by phycocyanin, whereas inhibition of both autophagy and apoptosis rescues phycocyanin-mediated cell death. Mechanistically, cell death induced by phycocyanin is the result of cross-talk among the MAPK, Akt/mTOR/p70S6K and NF-κB pathways. Phycocyanin is able to induce apoptosis of PANC-1 cell by activating p38 and JNK signaling pathways while inhibiting Erk pathway. On the other hand, phycocyanin promotes autophagic cell death by inhibiting PI3/Akt/mTOR signaling pathways. Furthermore, phycocyanin promotes the activation and nuclear translocation of NF-κB, which plays an important role in balancing phycocyanin-mediated apoptosis and autosis. In conclusion, our studies demonstrate that phycocyanin exerts anti-pancreatic cancer activity by inducing apoptotic and autophagic cell death, thereby identifying phycocyanin as a promising anti-pancreatic cancer agent.

Phycocyanin: A Potential Drug for Cancer Treatment

“…The anti- proliferation effect of phycocyanin is mediated by BCR-ABL signaling and inactivation of the downstream PI3K/Akt pathway 80 . In addition, MAPK, PI3K/Akt/mTOR and NF-κB pathways involved phycocyanin-induced cell death 81 .…”

Sorafenib and 2-Deoxyglucose Synergistically Inhibit Proliferation of Both Sorafenib-Sensitive and -Resistant HCC Cells by Inhibiting ATP Production

“…The relation between cellular ATP level and cell cycle inhibition is strengthened by the observed activation of AMPK that responds to alterations in cellular energy and inhibition of mTOR as well as its downstream kinases p70S6K and 4E-Bp (Figure 6A, B). Since these kinases are known to regulate cell cycle progression 21,23 , our data suggest that alteration in the activation state of these kinases as a result of changes in cellular ATP leads to the observed cell cycle arrest (Figure 4A, B). The drastic reduction in activation of these kinases corroborated with significant inhibition of cell cycle progression following combined treatment compared to treatments with individual drugs.…”

Spirulina extract enriched for Braun‐type lipoprotein (Immulina®) for inhibition of 4T1 breast tumors' growth and metastasis

“…Suwanwong, and P. Research, ) In addition, MAPK, PI3K/Akt/mTOR and NF‐κB pathways are involved in the phycocyanin‐induced cancer cells' apoptosis. (Jiang et al, ; Liao et al, ; Subhashini et al, ) In addition, this active compound of the Spirulina extract can alter the mitochondrial membrane potential, which can stimulate the release of cytochrome c and promote the formation of reactive oxygen species (ROS). These events ultimately lead to cancer cell apoptosis.…”