BINMEI, global leader in blue spirulina

Abstract: Incent years, the search for anti-tumor drugs with high efficiency, low toxicity, and little side effects in marine organisms has attracted the attention of scholars. C-phycocyanin (C-PC) has toxic and side effects on a variety of tumor cells, which can inhibit the growth of tumor cells and promote the apoptosis of tumor cells. Phycocyanin combined with other drugs can improve its anti-tumor activity. This review discusses the therapeutic use of phycocyanin and focuses on the latest advances of phycocyanin as a promising natural anti-cancer drug.

Keywords: C-phycocyanin; Union; Anti-tumor; Tumor cells

LIU Huihui, JIANG Liangqian, WANG Yujuan, LIU Guxiang, JI Huanhuan, REN Junyi, LI Bing

Department of Cell Biology, Basic Medical College, Qingdao University, Qingdao 266021, China

1. Introduction

In recent years, marine products have been proved to have good anticancer activity and almost no toxic side effects E.algal blue protein (c-phycocyanin, c-pc) is a bioactive nutrient count extracted from algae such as spirulina, sphingophyta, and algal, which is nutritious and can supplement human protein and vitamin e. The phycocyanin belongs to the phycocyanin (PBP) family, which consists mainly of subunits α and β.

Studies have shown that phycocyanin plays an important role in anti-tumor 3″ seven and has a wide range of medicinal value, anti-tumor, anti-oxidation, and anti-inflammatory activity. The phycocyanin also removes damaged nerve cell-free radicals and avoids oxidative DNA damage, thereby preventing free radical-induced neuronal apoptosis, phycocyanin also inhibits epithelial-mesenchymal transition (EMT). Besides, phycocyanin also has photoinduced cytotoxicity and immune stimulation, promoting the regeneration of animal blood cells, enhancing lymphocyte activity, and enhancing the body’s Immune function is 2 sentences, comprehensive improvement of the body’s disease resistance network, with drug development potential. Numerous studies have shown that phycocyanin has inhibitory effects on a variety of tumors, such as breast cancer liver cancer.

2. The individual action of phycocyanin

The phycocyanin is a photosynthetic auxiliary pigment-protein found in algal cells and has remarkable anti-tumor activity. Ying et al. actioned phycocyanin on ovarian cancer (SKOV-3) cells and found cells blocking the G2/M phase, indicating that phycocyanin could inhibit the proliferation of ovarian cancer cells. Liao et al. (iv) applied phycocyanin to pancreatic cancer (PDA) cells and found that with the increase of phycocyanin concentration, the cell activity gradually weakened. flow cytometry detection found that phycocyanin was able to block the cell cycle to the gym. phycocyanin acting on the pancreatic cancer mouse model, with the increase of phycocyanin concentration, mouse tumor tissue gradually decreased. Ying Jun et al. treated different concentrations of phycocyanin with HEP-2 cells in laryngeal cancer.MTT showed that phycocyanin inhibited HEP-2 cell viability and was time- and dose-dependent. Flow cytometry showed that phycocyanin significantly induced apoptosis in HEP-2 cells. real-time quantitative PCR (rt-PCR) results showed that the expression of pro-apoptotic protein Bax, fas, p53, caspase-3, and caspase-9 was significantly up-regulated and the expression of anti-apoptotic protein BCL-2 was significantly down-regulated after the action of phycocyanin; thus, the BCL-2/bax ratio of apoptotic cells decreased and the apoptotic cells were induced. HeLa cells containing the CD59 gene were constructed by using different doses of phycocyanin in vitro cultured HeLa cells. the effect of phycocyanin on cell cycle and apoptosis of HeLa cells was measured by flow cytometry. the results showed that the anti-apoptotic protein Bcl-2 was down-regulated after phycocyanin treatment, but the pro-apoptotic protein Bax was up-regulated or no change. therefore, the ratio of BCL-2/bax tended to cause apoptosis.

The above literature studies the antitumor effect and mechanism of phycocyanin, which lays a foundation for the next research.

3. Phycocyanin combined with photodynamic therapy Morcos and others have found that laser-induced

phycocyanin can be toxic to cells, and when the he-ne laser is applied to tumor cells, phycocyanin can play an important role in photodynamic therapy as a photosensitizer. Li et al found that phycocyanin combined with photodynamic therapy (PDT) promoted apoptosis of cancer cells in mice with MCF-7 tumor and provided a new direction for tumor treatment. phycocyanin acts as a photosensitizer. under 625 nm laser irradiation, phycocyanin induces a cytotoxic response of reactive oxygen species (ros) to induce apoptotic nets of MDA-MB-231 cells.

when phycocyanin combined with he-ne laser was used to treat hcc cell hepg2, phycocyanin could be used as a photosensitizer to induce mitochondrial membrane potential decrease, increase the content of reactive oxygen species (ros), release cytochrome c, promote the expression of the caspase-3 protein, induce cell cycle arrest and stimulate hepg2 cells to activate endogenous pathway to initiate apoptosis without any toxic side effects on healthy hepatocyte line hl7702 cells.

Li Bing et al.injected the tumor-bearing mice of HeLa cells with local subcutaneous injection of phycocyanin solution to produce an active oxygen ion with toxic effect after irradiation by nitrogen-actuated laser, thus destroying the tumor fineness. The laser can enhance the activity of NK cells and the proliferation of T cells, indicating that laser irradiation has anti-tumor and enhance the activity of immune cells. However, after the combination of C-PC and laser, the anti-tumor immune effect was significantly increased. Laser irradiation of tumor cell areas can promote the transmission of tumor death signal and improve the anti-tumor immunity of tumor-bearing bodies.

4. Phycocyanin combined with all-trans retinoic acid

All-trans retinoic acid (ATRA) inhibits tumor cell growth. However, due to the high concentration of ATRA side effects, the drug’s clinical use is greatly limited. At present, combined drug use is one of the important strategies to treat tumor clinically, its treatment principle is to reduce the emergence of drug resistance, reduce the adverse reactions of patients, and prolong the time of medication to improve the treatment. Li Bing (iv) combined C-PC and ATRA to explore the best effect of the two drugs. In vivo, MTT was used to detect the proliferation of HeLa and A549 cells when the two drugs were used alone and jointly. in vitro use of nu/nu nude mice to construct a tumor-bearing mouse model. after c-pc and atra drug treatment, mtt was used to detect the activity of t lymphocytes and spleen cells. The results showed that both drugs had a tumor inhibition effect, and the inhibition rate increased with the increase of drug concentration. C-PC can enhance the body’s immunity, when the combination of C-PC and ATRA, can effectively reduce the side effects of ATRA and tumor suppression effect is more significant.

Yang et al. found that combination therapy of all-trans retinoic acid and phycocyanin on HeLa cells significantly reduced the dosage and side effects of all-trans retinoic acid. the combination can significantly downregulate the expression of anti-apoptotic protein BCL-2, upregulate the expression of pro-apoptotic protein caspase-3, inhibit the expression of cell cycle-related proteins CDK-4 and cyclin d1, and inhibit the expression of complement regulatory protein cd59 and induce apoptosis.

Li et al. divided A549 cells into the control group, C-PC group, ATRA group, C-PC group, and ATRA group. After 24 hours of culture, the growth of A549 cells was detected by MTT colorimetry. The results showed that both C-PC and ATRA could inhibit the growth of A549 and positively correlated with the dose.

The antitumor effect of phycocyanin combined with all-trans retinoic acid was significantly enhanced, and both C-PC and ATRA could inhibit the growth of tumor cells. The combination of the two could reduce the concentration of ATRA, reduce the side effects, prolong the time of medication, and increase the ability of C-PC to resist tumor.

5. Phycocyanin in combination with other drugs

The combination of topotecan and phycocyanin at 10% conventional doses for prostate cancer (LNCAP) showed that the combination was far more effective than either alone. the combined use of phycocyanin and topotecan activates caspase-9 and caspase-3 expression activity increases oxygen free radical (ros) expression levels, induces apoptosis in tumor cells, and reduces side effects when topotecan is used alone.

Saini et al. treated DMH-induced colon cancer in rats with a combination of piroxicam (a traditional non-arabinoside anti-inflammatory drug) and phycocyanin. the results showed that the combined administration reduced the expression levels of DNA fragmentation, cyclooxygenase-2(cox-2), and prostaglandin e2(pge2). also, the number and volume of tumor cells were also significantly reduced.

When si, such as Bingula, combined with betaine and phycocyanin, used in lung cancer A549 cells, the activity of A549 cells decreased by 60 percent, much higher than when betaine or phycocyanin was used alone. the combination of betaine and phycocyanin reduced the expression of nf-kb and increased the expression of pro-apoptotic protein p38, causing cell g2/m cell cycle arrest. adriamycin combined with phycocyanin acted on adult rats. the results showed that adriamycin could significantly reduce the formation of reactive oxygen species (ros) and reduce the fragmentation of DNA, and the apoptosis rate was significantly reduced. therefore, phycocyanin reduces doxorubicin-induced oxidative stress with cardiomyocyte apoptosis nets.

6. New phycocyanin/MSG-CD59 ligand peptide nanomicrospheres targeting

It is found that phycocyanin has anti-tumor and anti-immune effects, but its poor stability and easy degradation in vivo limit its response in biomedical fields. Lu Cong instrument used posterior methyl chitosan (CMC) embedded in water-soluble phycocyanin to prepare phycocyanin/ spindle-based chitosan nanomicrospheres (C-PC/CMC-NPS) via CaCL-mediated ion crosslinking. Using flow cytometry to detect the apoptosis status of HeLa cells before and after dosing, it was found that C-PC, CMC, and C-PC/CMC-NPs could induce apoptosis, among which the apoptosis effect of C-PC/CMC-NPs was more obvious. Further experiments showed that C-PC, CMC, and C-PC/CMC-NPs could inhibit the expression of anti-apoptotic protein Bcl-2 and promote the expression of pro-apoptotic protein JNK and Caspase-3, among which the effect of C-PC/CMC-NPs was the most obvious. The molecular mechanism of C-PC/CMC-NPs inducing apoptosis in HeLa cells may be to promote the expression of JNK protein and Caspase-3 protein by inhibiting the expression of Bcl-2 protein, thus realizing the transmission of apoptotic signal in JNK signal transduction pathway and inducing apoptosis in tumor cells.

Yin Qifeng et al. net with C-PC as an anti-tumor model drug, CMC as a carrier, CD59 ligand peptide (CD59sp) as target molecule, C-PC was wrapped in CMC to prepare C-PC/CMC-NPs, and then CD59sp was connected to nanomicrospheres to synthesize the targeting drug C-PC/CMC-CD59sp-NPs to achieve the targeting delivery of nanospheres, and the targeting, safety and antitumor effect of nano-drug in tumor cells were studied. the cd59sp was attached to the nanomicrospheres to prepare targeted nanomedicines designed to achieve targeted docking and uptake of drugs under the guidance of cd59sp using the specific binding of cd59 ligand peptides and cd59 proteins on the surface of tumor cells. under the guidance of cd59sp, c-pc/CMC-cd59sp-NPS could target and efficiently reach the HeLa cell surface and significantly inhibit the proliferation of HeLa cells. this microsphere can promote the expression of caspase-3 and parp protein, inhibit the expression of Bcl-2 protein, and promote the intracellular transduction of apoptosis signal. at the same time, it is found that these nanomicrospheres can significantly inhibit the cell cycle progression and appear the phenomenon of gi phase block. Wang et al found that new C-PC/CMC-CD59sp nanomicrospheres can promote the apoptosis of tumor cells and inhibit the proliferation of tumor cells. novel c-pc/CMC-cd59sp-NPS nanomicrospheres with c-pc as an antitumor model drug, CMC as a carrier, and cd59sp as a target molecule for tumor targeting treatment. The nanomicrospheres can significantly reduce the degradation of C-PC, increase the stability of C-PC, change the dissolution rate of drugs, improve the utilization of drugs, and be able to maintain the effective concentration of drugs for a long time, to improve the efficacy of drugs and reduce toxic side effects. Using CD59sp specificity to bind to CD59, it can be used as a target guide molecule to connect to nanodrugs to achieve targeted drug delivery, but also to close CD59, promote the formation of MAC and enhance the antitumor effect.

7. Conclusion

The phycocyanin is widely used and has the function of obviously inhibiting tumor growth, which is non-toxic and efficient, but its content is low, its stability is poor, it is easy to degrade in vivo and its utilization rate is low, which limits its response. There are many problems in drug development with natural phycocyanin, such as high cost, high impurity, and long cycle. Its anti-tumor effect combined with other drugs needs to be further developed, in which the construction of targeted anti-tumor carrier system provides a new idea for drug research and development.