Anticancer Effects of Fucoxanthin through Cell Cycle Arrest, Apoptosis Induction, Angiogenesis Inhibition, and Autophagy Modulation

Abstract

Cancer accounts for one in seven deaths worldwide and is the second leading cause of death in the United States, after heart disease. One of the standard cancer treatments is chemotherapy which sometimes can lead to chemoresistance and treatment failure. Therefore, there is a great need for novel therapeutic approaches to treat these patients. Novel natural products have exhibited anticancer effects that may be beneficial in treating many kinds of cancer, having fewer side effects, low toxicity, and affordability. Numerous marine natural compounds have been found to inhibit molecular events and signaling pathways associated with various stages of cancer development. Fucoxanthin is a well-known marine carotenoid of the xanthophyll family with bioactive compounds. It is profusely found in brown seaweeds, providing more than 10% of the total creation of natural carotenoids. Fucoxanthin is found in edible brown seaweed macroalgae such as Undaria pinnatifida, Laminaria japonica, and Eisenia bicyclis. Many of fucoxanthin's pharmacological properties include antioxidant, anti-tumor, anti-inflammatory, antiobesity, anticancer, and antihypertensive effects. Fucoxanthin inhibits many cancer cell lines' proliferation, angiogenesis, migration, invasion, and metastasis. In addition, it modulates miRNA and induces cell cycle growth arrest, apoptosis, and autophagy. Moreover, the literature shows fucoxanthin's ability to inhibit cytokines and growth factors such as TNF-α and VEGF, which stimulates the activation of downstream signaling pathways such as PI3K/Akt autophagy, and pathways of apoptosis. This review highlights the different critical mechanisms by which fucoxanthin inhibits diverse cancer types, such as breast, prostate, gastric, lung, and bladder development and progression. Moreover, this article reviews the existing literature and provides critical supportive evidence for fucoxanthin's possible therapeutic use in cancer.

Keywords: apoptosis; autophagy; cancer; carotenoids; fucoxanthin.

Figure 1

Natural compounds and their chemopreventive effects on cancer.

Figure 2

The chemical structure of fucoxanthin [89].

Figure 3

Fucoxanthin metabolism to fucoxanthinol and amarouciaxanthin A [100].

Figure 4

The proposed effect of fucoxanthin on the extrinsic (death receptor) and intrinsic (mitochondrial) pathways of apoptosis. Red arrows indicate that inhibition is induced by fucoxanthin, and green arrows indicate activation is induced by fucoxanthin.

Figure 5

Proposed effects of fucoxanthin on PI3K/Akt signaling and mediated antiapoptotic regulation. Red arrows indicate that inhibition is induced by fucoxanthin, and green arrows indicate activation is induced by fucoxanthin.

Figure 6

The proposed effect of fucoxanthin on autophagosome production. Red arrows indicate that inhibition is induced by fucoxanthin, and green arrows indicate activation is induced by fucoxanthin.

Figure 7

The proposed effect of fucoxanthin on miRNA. The red arrow indicates that inhibition is induced by fucoxanthin. miRNAs are developed from pri-miRNAs that are transcribed from other independent miRNA genes.

Figure 8

Proposed fucoxanthin action on cancer progression and development by modulating diverse signaling transduction pathways. Red arrows indicate that inhibition is induced by fucoxanthin, and green arrows indicate activation is induced by fucoxanthin.