The anticancer effects and mechanisms of fucoxanthin combined with other drugs
- 48 Downloads
Fucoxanthin (Fx) is a characteristic carotenoid present in brown seaweed that has been shown to have various benefits, including anticancer effects. In vitro studies demonstrated these various effects, including the suppression of cell viability, the promotion of apoptosis, and antiangiogenic, antiproliferative, and antimetastatic activity. Interestingly, combinations of Fx with other drugs have better effects than either Fx or other drugs alone. Although the antiproliferative and cancer prevention activities of the combination of Fx and other drugs are still unclear, several effects have been discovered, including the induction of apoptosis, cell cycle arrest at G1/G0, enhanced gap junctional intercellular communication, and the induction of autophagy via various mechanisms, such as decreasing P-gp, activating the CYP3A4 promoter, increasing reactive oxygen species and cellular uptake and suppressing the PI3K/Akt/NFκB pathway. In this review, we address the anticancer effects and mechanisms of the combination of Fx and other drugs in different types of cancer.
The relevant literature from PubMed and Web of Science databases is reviewed in this article.
Fx combined with other drugs could enhance the effect of both Fx and the other drug or reduce the dose without reducing the effect, which may create more effective and less harmful therapeutic strategies.
Fx combined with other drugs has significant anticancer effects by various mechanisms and could be a potential therapeutic strategy for different types of cancer.
KeywordsFucoxanthin Troglitazone 5-Fluorouracil Pregnane X receptor Imatinib
Protein kinase B
Mammalian target of rapamycin
B-cell lymphoma 2
c-Jun N-terminal kinases
Signal transducer and activator of transcription protein family
Nuclear factor kappa-light-chain-enhancer of activated B cells
Mitogen-activated protein kinase
Pregnane X receptor
Cyclin-dependent kinase inhibitor 1
Peroxisome proliferator-activated receptor γ
- ABC transporters
ATP-binding cassette transporters
Multidrug resistance protein
Reactive oxygen species
Bcl-2-associated X protein
Growth arrest and DNA-damage-inducible protein
Cytochrome P450 3A4
Steroid receptor coactivator-1
Excision repair cross complementation 1
Extracellular signal-regulated kinase
Adult T-cell leukemia
X-linked inhibitor of apoptosis protein
Cellular inhibitor of apoptosis protein 2
Nuclear factor of kappa light polypeptide gene enhancer in B-cell inhibitorα
B-cell lymphoma-extra large
Chronic myelogenous leukemia
Breakpoint cluster region protein
Abelson murine leukemia viral oncogene homolog
Phosphatase and tensin homolog
Tumor necrosis factor-related apoptosis-inducing ligand
Tumor necrosis factor
We thank Rong Xu, Jiaxiong Ming, Huan Zhang, Yuyue Zuo, Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, for advice on the article.
This study was funded by National Natural Science Foundation of Wuhan (Grant no. WX18Q21 to YC).
Compliance with ethical standards
Conflict of interest
Authors declare that he/she have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
- Almeida TP, Ferreira J, Vettorazzi A, Azqueta A, Rocha E, Ramos AA (2018) Cytotoxic activity of fucoxanthin, alone and in combination with the cancer drugs imatinib and doxorubicin, in CML cell lines. Environ Toxicol Pharmacol 59:24–33. https://doi.org/10.1016/j.etap.2018.02.006 CrossRefGoogle Scholar
- Aoki H, Takada Y, Kondo S, Sawaya R, Aggarwal BB, Kondo Y (2007) Evidence that curcumin suppresses the growth of malignant gliomas in vitro and in vivo through induction of autophagy: role of Akt and extracellular signal-regulated kinase signaling pathways. Mol Pharmacol 72:29–39. https://doi.org/10.1124/mol.106.033167 CrossRefGoogle Scholar
- Dussault I, Forman BM (2002) The nuclear receptor PXR: a master regulator of “homeland” defense. Crit Rev Eukaryot Gene Expr 12:53–64Google Scholar
- Hosokawa M, Kudo M, Maeda H, Kohno H, Tanaka T, Miyashita K (2004) Fucoxanthin induces apoptosis and enhances the antiproliferative effect of the PPARgamma ligand, troglitazone, on colon cancer cells. Biochim Biophys Acta 1675:113–119. https://doi.org/10.1016/j.bbagen.2004.08.012 CrossRefGoogle Scholar
- Jin Y, Qiu S, Shao N, Zheng J (2018) Fucoxanthin and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) synergistically promotes apoptosis of human cervical cancer cells by targeting PI3K/Akt/NF-κB signaling pathway. Med Sci Monit 24:11–18. https://doi.org/10.12659/msm.905360 CrossRefGoogle Scholar
- Kim KN, Heo SJ, Yoon WJ, Kang SM, Ahn G, Yi TH, Jeon YJ (2010b) Fucoxanthin inhibits the inflammatory response by suppressing the activation of NF-kappaB and MAPKs in lipopolysaccharide-induced RAW 264.7 macrophages. Eur J Pharmacol 649:369–375. https://doi.org/10.1016/j.ejphar.2010.09.032 CrossRefGoogle Scholar
- Liu C-L, Huang Y-S, Hosokawa M, Miyashita K, Hu M-L (2009) Inhibition of proliferation of a hepatoma cell line by fucoxanthin in relation to cell cycle arrest and enhanced gap junctional intercellular communication. Chem Biol Interact 182:165–172. https://doi.org/10.1016/j.cbi.2009.08.017 CrossRefGoogle Scholar
- Liu C-L, Lim Y-P, Hu M-L (2012) Fucoxanthin attenuates rifampin-induced cytochrome P450 3A4 (CYP3A4) and multiple drug resistance 1 (MDR1) gene expression through pregnane X receptor (PXR)-mediated pathways in human hepatoma HepG2 and colon adenocarcinoma LS174T cells. Mar Drugs 10:242–257. https://doi.org/10.3390/md10010242 CrossRefGoogle Scholar
- Liu Y, Zheng J, Zhang Y, Wang Z, Yang Y, Bai M, Dai Y (2016) Fucoxanthin activates apoptosis via inhibition of PI3K/Akt/mTOR pathway and suppresses invasion and migration by restriction of p38-MMP-2/9 pathway in human glioblastoma cells. Neurochem Res 41:2728–2751. https://doi.org/10.1007/s11064-016-1989-7 CrossRefGoogle Scholar
- Mahon FX, Deininger MW, Schultheis B, Chabrol J, Reiffers J, Goldman JM, Melo JV (2000) Selection and characterization of BCR-ABL positive cell lines with differential sensitivity to the tyrosine kinase inhibitor STI571: diverse mechanisms of resistance. Blood 96:1070–1079Google Scholar
- Ravi H, Kurrey N, Manabe Y, Sugawara T, Baskaran V (2018) Polymeric chitosan-glycolipid nanocarriers for an effective delivery of marine carotenoid fucoxanthin for induction of apoptosis in human colon cancer cells (Caco-2 cells). Mater Sci Eng C Mater Biol Appl 91:785–795. https://doi.org/10.1016/j.msec.2018.06.018 CrossRefGoogle Scholar
- Rwigemera A, Mamelona J, Martin LJ (2014) Inhibitory effects of fucoxanthinol on the viability of human breast cancer cell lines MCF-7 and MDA-MB-231 are correlated with modulation of the NF-kappaB pathway. Cell Biol Toxicol 30:157–167. https://doi.org/10.1007/s10565-014-9277-2 CrossRefGoogle Scholar
- Saegusa M, Hashimura M, Suzuki E, Yoshida T, Kuwata T (2012) Transcriptional up-regulation of Sox9 by NF-kappaB in endometrial carcinoma cells, modulating cell proliferation through alteration in the p14(ARF)/p53/p21(WAF1) pathway. Am J Pathol 181:684–692. https://doi.org/10.1016/j.ajpath.2012.05.008 CrossRefGoogle Scholar
- Wang J, Chen S, Xu S, Yu X, Ma D, Hu X, Cao X (2012) In vivo induction of apoptosis by fucoxanthin, a marine carotenoid, associated with down-regulating STAT3/EGFR signaling in sarcoma 180 (S180) xenografts-bearing mice. Mar Drugs 10:2055–2068. https://doi.org/10.3390/md10092055 CrossRefGoogle Scholar
- Ye GL, Du DL, Jin LJ, Wang LL (2017) Sensitization of TRAIL-resistant cervical cancer cells through combination of TRAIL and fucoxanthin treatments. Eur Rev Med Pharmacol Sci 21:5594–5601Google Scholar
- Yoshiko S, Hoyoku N (2007) Fucoxanthin, a natural carotenoid, induces G1 arrest and GADD45 gene expression in human cancer cells. In Vivo 21:305–309Google Scholar