Table 2.

Bioactive compounds of P. oleracea, types of extracts, and molecular mechanisms for cancer inhibition.

Experimental model		Compounds	Types of extract	Types of cancer inhibited	Mechanisms and results	References
In vitro	In vivo
	Rats	Polysaccharides	Aqueous extract	Ovarian	Scavenge superoxide anion, (DPPH-), nitric oxide, and hydroxyl radicals Inhibit RBC hemolysis Spleen, thymocyte, T and B lymphocyte proliferation	[19]
Human cancer cell lines SF-268, NCI-H460, K-562, SGC-7901, and SMMC-7721		Homoisoflavonoids	Hydroalcoholic extract		Homoisoflavonoids showed in vitro cytotoxic activities towards four human cancer cell lines	[61]
Treatment of HeLa cell	Mice	Polysaccharides	Aqueous extract	Cervical	Sub-G1 phase cell cycle arrest, triggering DNA damage Inducing apoptosis	[21]
	Mice	Polysaccharides	Aqueous extract		Inhibit the growth of transplantable sarcoma 180 Increase in the number of white blood cells (WBC) and CD4+ T-lymphocytes Increase in the CD4+/CD8+ ratio	[20]
	Rats	Polysaccharides	Aqueous extract	Gastric	Interleukin-2 (IL-2), interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF-α) was enhanced Provide dose-dependent protection against MNNG-induced oxidative injury by enhancing SOD, CAT, GSH-Px	[22]
Human lung (K562 and A549) and breast (MCF-7 and MDA-MB-435) cancer cell lines		Alkaloids	Hydroalcoholic extract	Lung Breast	Moderate cytotoxic activities against A549 and weak cytotoxic activities against K562. The compounds showed low cytotoxic activity against MCF-7 and MDA-MB-435 cells.	[54]
Human hepatocellular carcinoma cells			Seed alcoholic extract	Hepatocellular	Significantly reduced the cell viability of HepG2.	[15]
The uterine cervical carcinoma (U14) cell line		Polysaccharides	Aqueous extract	Cervical	Upregulated the expression of CD80, CD86, CD83 Increase in IL-12, TLR-4, Decrease in IL-10	[29]
Human HL60 cell line		Portulacerebroside A	Aqueous extract	Leukemia	Mitochondrial membrane potential ROS accumulated Increase in RNA expressions and protein levels of Bax/Bcl-2, caspase-3, and caspase-9 ERK1/2, JNK1/2 and p38 MAPK pathway were blocked	[49]
HepG2 and A-549 cell lines			Seed oil	Liver Lung	Significant cytotoxicity and inhibition of growth of the liver cancer (HepG2) and lung cancer (A-549) cell lines	[20]
Human liver cancer HCCLM3 cells		Portulacerebroside A	Aqueous extract	Liver	Increase in RNA and protein expression levels of TIMP-2 and nm23-H1 Inhibition of the mRNA expression of MTA1, MMP-2, and MMP-9 Suppression of the protein expression of MTA1, RhoA, Rac1/Cdc42, MMP-2, but not RhoC and MMP-9	[23]
Cervical cancer HeLa cells, esophageal cancer Eca-109 cells and breast cancer MCF-7 cells			Seed oil	Cervical Esophageal Breast	Stronger inhibitory effect on the proliferation of MCF-7 cells and significantly inhibited the proliferation of HeLa cells and Eca-109 cells	[51]
PANC-1 cancer cell line			Aqueous extract	Pancreatic	Significant effect on apoptosis in pancreatic cell line and high expression of P53 and reduction of CDK gene expression	[23]
Human colon adenocarcinoma (HCT-15) and normal (Vero) cell line			Chloroform extract	Colon adenocarcinoma	Chloroform extract does not have cytotoxic activity and was not safe to normal Vero cell line.	[67]
Colon cancer cells (HT-29) and HT-29 cancer stem cells			Ethyl alcohol extract	Colon Stem cells	Inhibited the proliferation of both HT-29 cancer cells and HT-29 cancer stem cells Significantly decreased the expression of the Notch1 and β-catenin genes in both cell types	[52]
The human cervical cancer HeLa cells.		Polysaccharides	Aqueous extract	Cervical	Decrease HeLa cell proliferation Upregulate Bax level and downregulate Bcl-2 level in a concentration-dependent manner Inhibit the protein expression levels of TLR4, MyD88, TRAF6, AP-1 and NF-κB subunit P65 Reduce the production of cytokine/chemokine	[50]
The mouse cervical carcinoma U14 cells		Polysaccharides	Aqueous extract	Intestinal	Dendritic cell (DC) apoptosis in U14-bearing mice Increase intestinal DC survival Stimulate the TLR4-PI3K/AKT-NF-κB signaling pathway	[48]
Human glioblastoma cancer cell line (U-87)			Hydroethanolic extract		Cytotoxicity and apoptogenic effects Anti-NF-κB activity along with two upstream ROS and NO mechanisms	[17]