Table 4.

The mechanism of some natural pigments for anti-cancer activity.

Cancers	Compounds Name	Category	Mechanism	Refs.
Breast cancer	Lycopene	Carotenoids	Activation of ERK1/2, ↓ cyclin D1 ↑ p21 ↓ phosphorylation of Akt and its downstream molecule mTOR ↑ Bax	[154]
	β-Carotene	Carotenoids	↑ Apoptosis ↓ cell cycle ↓ PI3K/Akt ↓ ERK	[155,156]
	Lutein	Carotenoids	↓ Breast cancer cell proliferation, ↑ expression of cellular antioxidant enzymes, ↓ ROS, ↑ NrF2/ARE pathway, ↓ NF-κB signaling pathway ↑ p53, ↓ HSP60	[157,158]
	Crocin	Carotenoids	↑ Disrupting the microtubule network ↓ Wnt/β-catenin target genes	[159,160]
	Astaxanthin	Carotenoids	↓ Cellular migration, ↓ cell number ↓ Expression levels of pontin, mutp53, Oct4, and Nanog, ↓ proliferation Activation of Bax/Bcl2, cleaved caspase-3, and cleaved caspase-9 as well as the phosphorylation of ERK1/2, JNK, and p38	[143,144,145]
	D-3-5-D, C3R	Polyphenols	↑ Intracellular reactive oxygen, ↑ apoptosis ↓ MCF-7 cells in the G2/M phases	[161]
	C3G, Pg-3-G	Polyphenols	↓ AMPK, ↑ apoptosis ↑ Oxidative stress	[162]
	Curcumin	Polyphenols	↓ NF-κB signaling pathway ↓ HER2-TK ↓ Akt protein, ↓ ubiquitin-proteasome pathway ↓ PI3K/Akt signaling pathway ↓ EGFR signaling	[163,164,165,166,167]
	Betanin	Alkaloids	↑ Apoptosis-related proteins (Bad, TRAILR4, FAS, p53)	[168]
Colorectal Cancer	Astaxanthin	Carotenoids	↓ Invadopodia, ↓ EMT, ↑ E-cadherin, ↓ vimentin, ↓ cortactin, ↓ MMP2, ↑ miR-29a-3p, ↓ ZEB1, ↓ MYC ↑ Apoptosis, ↑ Bax, ↑ caspase-3, ↓ Bcl2	[169,170]
	Fucoxanthin	Carotenoids	↓ Proliferation ↑ DNA damage	[171,172]
	Crocin	Carotenoids	↑ Caspase-3 and -7, ↓ proliferation	[173]
	C3G, C3XR, C3R	Polyphenols	↑ Probiotics, ↓ inflammation ↓ Pathogenic bacteria	[174]
	C3G, C3XR, C3R	Polyphenols	↑ MiR-24-1-5p, ↓ β-catenin	[175]
	Pg-3-G	Polyphenols	↓ HT-29 colon cancer cells	[176]
	Anthocyanin extract	Polyphenols	↓ Wnt/β-catenin ↓ Mitochondrion-mediated apoptosis	[146]
	Curcumin	Polyphenols	↓ NF-κB pathway, ↓ cell cycle ↑ Cytochrome c, ↑ Bax and p53, ↓ Bcl-2	[177,178]
	Betaxanthin and betacyanin	Alkaloids	↓ Bcl2-like protein 4, ↓ cleaved poly ADP-ribosyl polymerase 1, ↓ cleaved caspase-3 ↓ Anti-apoptotic protein B-cell leukemia/lymphoma 2 levels	[179]
Gastric cancer	Crocin	Carotenoids	↓ KLF5 HIF-1, ↑ miR-320, ↓ epithelial–mesenchymal transition, ↓ migration	[180]
	β-Carotene	Carotenoids	↓ Cell viability, ↑ DNA damage, ↑ apoptotic indices, ↑ caspase-3, ↓ Ku70/80	[181]
	Fucoxanthin	Carotenoids	↑ Beclin-1, ↑ LC3, ↑ cleaved caspase-3 (CC3), ↓ Bcl-2, ↓ cell cycle, ↑ apoptosis, ↓ Mcl-1, STAT3, and p-STAT3	[182,183]
	Astaxanthin	Carotenoids	↓ Cell cycle ↑ NADPH oxidase activity, ↑ ROS levels, ↑ LDH release, ↑ the number of propidium iodide-positive cells ↑ RIP1/RIP3/MLKL signaling pathway	[184,185]
	Curcumin	Polyphenols	↓ STAT3 pathway	[178]
Liver cancer	Astaxanthin	Carotenoids	↑ Cell number in G2 phase ↑ Cell number in G2/M phase ↑ Apoptosis ↑ Oxidative stress, ↑ adiponectin	[186,187,188]
	Crocin	Carotenoids	↓ NF-κB, ↓ inflammation, ↓ cell cycle, ↑ apoptosis	[189]
	Fucoxanthin	Carotenoids	↓ Glutathione (GSH) content, ↓ proliferation Reverting body weight, serum albumin, antioxidant enzymes, all the liver enzymes, serum bilirubin, and stress markers to normal levels in hepatocellular carcinoma rats	[190,191]
	C3G, Pn-3-G	Polyphenols	↓ TNF-α, iNOS, NF-κB ↓ Cell proliferation	[192]
	C3G, C3R	Polyphenols	↓ Lipid peroxidation, ↓ COX-2 ↑ Nrf2-mediated antioxidant enzymes	[193]
	M3G	Polyphenols	↓ Proliferation, ↑ apoptosis, ↓ ROS, ↑ JNK/p38 MAPK pathways, ↓ AKT phosphorylation, ↓ migration, ↓ invasion	[147]
	Curcumin	Polyphenols	↓ Migration, ↓ invasion, ↓ epithelial–mesenchymal transition, ↓ aryl hydrocarbon receptor/ERK/SK1/S1P3 signaling pathway	[194]
	Betanin	Alkaloids	↑ Nrf2, ↑ mitogen-activated protein kinases	[195]
Lung cancer	Astaxanthin	Carotenoids	↑ Cell number in G0/G1 phase ↑ p38 MAPK ↑ Apoptosis	[196]
	Crocin	Carotenoids	↑ G0/G1 arrest, ↑ mRNA levels of p53 and Bax, ↓ Bcl-2, ↑ apoptosis	[197]
	Lutein	Carotenoids	↓ PI3K/AKT, ↑ apoptosis	[198]
	C3G	Polyphenols	↓ Lung tumor multiplicity and tumor area, ↓ expression of proliferative cell nuclear antigen (PCNA) and Ki-67	[199]
	Curcumin	Polyphenols	↓ NF-κB, ↓ JAK2/STAT3 signaling pathway, ↓ JAK2 ↓ Cell proliferation, ↑ apoptosis ↑ microRNA-192-5p, ↓ PI3K/Akt signaling pathway ↓ Wnt/β-catenin pathway	[150,151,152,153]
	Betalain	Alkaloids	↑ Proliferation, ↓ cell cycles, ↑ p53/p21, ↓ levels of cyclin-D1 complex, ↓ levels of p-PI3K, ↓ p-Akt, ↓ mammalian target of rapamycin	[200]
Prostate cancer	Astaxanthin	Carotenoids	↑ Apoptosis, ↑ cleaved caspase-3; ↑ miR-375 and miR-487b	[201]
	Crocin	Carotenoids	↓ Proliferation, ↓ cell cycle, ↑ apoptosis ↓ Bcl-2, ↓ Bax	[202]
	Proanthocyanidins	Polyphenols	↓ Notch1 pathway	[203]
	C3G	Polyphenols	↓ Epithelial–mesenchymal transition	[204]
	Curcumin	Polyphenols	↓ Expression of CYP11A1 and HSD3B2, ↑ AKR1C2, ↓ dihydrotestos terone ↑ miR-34a, ↓ β-catenin, ↓ c-myc	[205,206]