Review Article

Antiproliferative Effects of Honey and of Its Polyphenols: A Review

Table 2

Summary of in vitro studies of honey polyphenols.

CompoundCell line testedObservation/resultReference no.

CA, MC, PEDMC, PECHT -29Toxicity:
CA 2500  M
PEC 60  M
PEDMC 60  M
MC 225  M
Inhibition of DNA/RNA:
150  M MC, 40  M PEC and 20  M PEDMC
TPK activity downregulation:
100  M of MC, 30  M of PEC and 20  M of PEDMC
ODC activity downregulation:
150  M MC, 40  M PEC and 20  M PEDMC
[38]

CAPEHeLa [40]

CAPEU-937(a) Maximum inhibition of NF B at 25  g/mL after TNF treatment
(b) No inhibitory effect on AP-1, TFIID, and Oct-1
(c) Structural analogue 5, 6 dihydroxy strongly inhibited the NF- B
[41]

CAPEC6 glioma (a) DNA fragmentation at 50  M after 24 hours
(b) p-p53 , active Caspase 3 , Bak and Bax , Bcl2
[42]

CA, CAPEHepG2(a) CA and CAPE inhibited MMP-2 and 9 with IC50 of 10–20  M and 2–5  M
(b) CA at the concentration of 200  g/mL reduced the cell viability to 61% viability compared to the controls, and the treatment with CAPE (20  g/mL) in HepG2 cells reduced the viability to 72% of the controls
[43]

CAPEHT 1080(a) m-RNA levels of MMP-2 and MMP-9 were inhibited
(b) m-RNA levels of TIMP-1 and MT-1 MMP level decreased
[44]

ChrysinC-6 glioma (a) 72 hours of incubation with 50  M of chrysin, inhibited 90% of cell-proliferation
(b) levels increased , CDK2 and CDK4 were inhibited
[47]

ChrysinU-937(a) PLC- and active Caspase-3 level increased
(b) XIAP level decreased whereas cytochome-C level
[48]

GalanginHL-60(a) Galangin of 1–10  M also promoted antiproliferative effect which is evident after 48 hours of incubation
(b) Active Caspase 3 , a hallmark of apoptosis process, was detected after 24 hours and 72 hours of incubation with 50 and 10  M of galangin respectively
(c) Cell cycle analysis indicated the increase in the subG1 phase of galangin ( 10  M) treated cells
[50]
QuercetinHL-60(a) Quercetin had a remarkable inhibitory effect on the activities of cytosolic PKC and membrane TPK from HL-60 cells in vitro, with IC50 values of about 30.9 and 20.1  M, respectively
(b) Quercetin repressed the complete activity of phosphoinositides like PI, PIP, and PIP2 at the concentration of 80  M
[51]

QuercetinA-549(a) Quercetin in low concentration (1–20  M) promoted the cell proliferation whereas higher concentration (50–200  M) showed the concentration dependent cyotoxicity
(b) Increase in TAC of cell extracts but higher concentrations of the quercetin led to a progressive decrease in the TAC
[53]

Quercetin K562(a) reduction of c-myc and Ki-ras oncogenes
(b) fall in Inositol-1,4,5-triphosphate (IPs) concentrations
[52]

Quercetin Glioma cell(a) arrested the glioma cells in the G2 checkpoint of the cell cycle
(b) decreased the mitotic index
[54]

QuercetinMCF-7(a) IC50 value of 10  g/mL
(b) cell cycle arrest at G2/M phase
(c) inhibited the tumor growth by more than 58% in mice grafted with mammary carcinoma
[55]

AcacetinHEPG2(a) IC50 value = 10.44  g/mL
(b) p53 , , FasL , mFasL , sFasL and Bax
[58]

AcacetinA-549(a) IC50 value = 9.46  M
(b) p53 , , FasL , mFasL , sFasL and Bax
[57]

KaempferolHL-60(a) Mitochondrial potential decreased caspase-3 level increased
(b) Kaempferol growth inhibitory effect on HL-60 leukemia cells is due to heterogeneous response mainly dominated by cell cycle alternation although some degree of cytotoxicity results from apoptotic as well as nonapoptotic process
[60]

PinocembrinHCT116(a) Mitochondrial potential decreased
(b) BAX translocates in to mitochondria
(c) Cyt-C release
(d) Caspase-3 and Caspase 9 level increased
[61]

PinobanksinRat liver Mitochondria(a) Inhibits the mitochondria membrane permeability transition
(b) Lowers the lipid peroxidation
[62]

ApigeninColon cancer(a) inhibition of kinase
(b) cyclin B1
(c) IC50 values:
HT 29 = 50  M
SW480 = 40  M
Cac0-2 = 70  M
[63]

ApigeninBreast Cancer(a) inhibiting the HER2/neu-overexpressing cells (MDA-MB-453 cells) compared to basal level HER2/neu-expressing cells (MCF-7)[64]

Apigenin Hela(a) IC50 = 35.89  M
(b) p21/WAF1
(c) p53 and caspase-3 increased
(d) Bcl2 decreased
[65]
ApigeninNeuroblastoma(a) EC50 = 35  mol/L in NUB-7
(b) EC50 = 22  mol/L in LAN-5
(c) p53 and
(d) Bax
[66]

Apigenin Liver cancer(a) IC50 was observed to be 8.02  g/mL for HepG2, 2.16  g/mL for Hep3B and 22.73  g/mL for PLC/PRF/5
(b) G2/M cell cycle arrest
(c) Increase of p53 and p21/WAF1
[67]