Table 4.

Condensed tannins that could improve the chemosensitivity of cancer drugs.

Molecules	Origins	Experimental Approaches	Key Results	References
Proanthocyanidins	Chinese bayberry leaves	Platinum-resistant human ovarian cancer cell line OVCAR-3 Flow cytometry MTT assay Colony formation assay Western blot assay	Induced inhibitory effects on the growth and CSC characteristics of OVCAR−3 SP cells Reduced the expression of β-catenin, cyclin D1, and c-Myc and inhibited the self-renewal capacity of cells Induced G1 cell cycle arrest in OVCAR−3 SP cells	[58]
	Grape seed extract	Colorectal cancer cell lines, HCT116 and H716 Cell cycle and apoptosis analysis Cell viability and proliferation mRNA expression analysis Genome-wide RNA-sequencing analysisXenograft animal experiments	Sensitized acquired (HCT116-FOr cells) and innately chemoresistant (H716 cells) cancer cells to 5-FU and oxaliplatin (OXP) PCs + (5-FU and OXP) inhibited the growth of chemoresistant cells and decreased the expression of several key adenosine triphosphate-binding cassette (ABC) transporters Sensitized chemoresistant cells to 5-FU and OXPPCs + (5-FU and OXP) reduced chemoresistant xenograft tumor growth in mice	[59]
Tannic acid	Purchased	Malignant human cholangiocytes Calcein retention assays Western blot analysis RT-PCR	Decreased malignant cholangiocyte growth Exhibited a synergistic effect with mitomycin C and 5-FU but not with Gem Decreased calcein efflux and expression of PGP, MRP1, and MRP2 membrane efflux pumps	[60]
	Purchased	Liver cancer cell line HepG2 MTT assay Mitochondrial transmembrane potential qRT-PCR Western blot analysis	Inhibited HepG2 cell growth TA + CP induced mitochondria-mediated apoptosis in HepG2 cells and enhanced growth inhibitory effect compared to treatment alone	[61]
Procyanidins	Not reported	Laryngeal cancer cell line TU686 Flow cytometry Cell immunofluorescence staining Western blot analysis	Inhibited TU686 cells in a concentration-dependent manner for 24 h Induced apoptosis of TU686 cells Increased expression of LC3−Ⅱ and Caspase-3	[62]
Ellagic acid	Purchased	Colorectal carcinoma HT−29, Colo 320DM, SW480, and LoVo cells Trypan blue exclusion Annexin−V labeling Mitochondrial membrane potential (Δψm) Immunoblotting	EA + 5-FU inhibited cell proliferation of HT-29, Colo 320DM and SW480 cells EA + 5-FU increased apoptotic cell death of HT−29 and Colo 320DM cells EA potentiated 5-FU chemosensitivity in at least three colorectal cancer cell lines	[47]
	Purchased	Epithelial ovarian cancer cell line A2780MTT assay Immunoblot analysis Signal pathway analysis Cell cycle analysis	Enhanced CP cytotoxicity in A2780CisR cells Prevented the development of CP resistance	[48]
	Purchased	Caco-2 and HTC-116 cells MTT assay In vitro drug release Male New Zealand white rabbits	Induced higher cell viability than EA-NP treated HCT−116 cells Oral administration of EA-NPs caused a 3.6-fold increase in the area under the curve compared to that of EA (in vivo)	[63]
	Purchased	Rat C6 glioma cells Immunohistochemistry RT-PCR	Reduced MGMT expression Affected the apoptotic proteins of p53 and caspase-3 at the protein level, but not at the gene level EA + bevacizumab (BEV) reduced cell viability EA + BEV reduced MDR1 expression only at 72 h	[64]
	Purchased	Rat C6 glioma cells Immunocytochemistry RT-PCR	EA + TMZ reduced cell viability Down-regulated MGMT expression independent of the presence of TMZ EA + TMZ reduced MDR1 expression only over 48 h compared to TMZ alone Up-regulated caspase-3 at 48 h, but up-regulated p53 at 48 and 72 h EA + TMZ enhanced immunoreactivities of p53 and caspase-3 proteins, but not of the genes	[65]
	Purchased	Four human bladder cancer cell lines, TSGH−8301, TSGH-9202, T24, and J82 MTT assay Flow cytometry Cell migration and invasion assays Western blot analysis qRT−PCR Xenograft model	Induced high cytotoxicity of Gem in GEM−resistant cells EA + Gem increased apoptosis and reduced cell motility in GCB-resistant cells Resensitized bladder cancer cells to Gem by reducing the epithelial–mesenchymal transition Reduced EMT by inhibiting the TGFβ−SMAD2/3 upward signaling pathway Inhibited the growth of bladder cancer tumors and increased the in vivo inhibitory effects of Gen on tumors	[66]