| Properties | Information | |
|---|---|---|
| PhytoCAT-ID | PhytoCAT-1497 | |
| Phytochemical name or plant extracts | Hesperetin | |
| PMID | 18197618 | |
| Literature evidence | Naringenin activated both ERalpha and ERbeta, whereas hesperetin exhibited stronger potential to activate ERalpha rather than ERbeta. | |
| IUPAC name | (2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-2,3-dihydrochromen-4-one | |
| Phytochemicals’ class or type of plant extracts | Flavonoid | |
| Source of phytochemicals or plant Extracts | Citrus plant | |
| Geographical availability | NA | |
| Plant parts | NA | |
| Other cancers | Breast cancer | |
| Target gene or protein | CDK4, P21, Caspase 9, caspace-3, Bax, Bcl-2, eNOS, aromatase, p53, PPARG, NOTCH1, CDK2, Cyclin D, Mir-486-5p And H19 Lncrna, ICAM-1, HER2 | |
| Gene or Protein evidence | Regulation of CDK4 and p21(Cip1)1 may participate in the anticancer activity pathway of hesperetin in MCF-7 cells. In addition, hesperetin also induced apoptosis in triple negative breast cancer MDA-MB-231 cells via intrinsic pathway via activation of caspase -9 and -3 and increase in Bax:Bcl-2, Real-time reverse transcription polymerase chain reaction (RT-PCR) and western-blotting analysis revealed that hesperetin up-regulated endothelium nitric oxide synthase (eNOS) expression. In conclusion, the present study showed that hesperetin could decrease expression of aromatase at low concentrations in MCF-7 breast cancer cells. Moreover, hesperetin treatment modulates the expression of p53, PPARG, and NOTCH1. Hesperetin treatment at high concentration for 72 h resulted in a decrease in CDK2 and CDK4 together with cyclin D. Hindering The Synchronization Between Mir-486-5p And H19 Lncrna By Hesperetin Halts Breast Cancer Aggressiveness Through Tuning ICAM-1. The study identified two citrus fruit flavonoids, NG and HP as HER2-TK inhibitors and this is the first report on their potential to target preferentially and sensitize HER2 positive cancer cells to cell death. | |
| Target pathways | Taken together, our data suggest for the first time that the regulation of CDK4 and p21(Cip1)1 may participate in the anticancer activity pathway of hesperetin in MCF-7 cells. Silencing of ASK1 resulted in significant attenuation of JNK activation as well as reversed the hesperetin-mediated apoptosis suggesting that hesperetin-mediated apoptosis of MCF-7 cells involves accumulation of ROS and activation of ASK1/JNK pathway. | |
| IC50 | IC50 value from 4.7 ?grams/ml (quercetin + hesperetin, quercetin + naringenin) to 22.5 µgrams/ml (naringenin + hesperetin) in MCF-7 cell line. | |
| Potency | Hesperetin induced G1-phase cell cycle arrest in human breast cancer MCF-7 cells: involvement of CDK4 and p21. | |
| Cell line/ mice model | MCF-7, MDA-MB-435 | |
| Additional information | In conclusion, the encapsulation of hesperetin in liposomes does not interfere with therapeutic efficacy and provides a biocompatible alternative to toxic solubilizing agents, thereby enabling future clinical use of this compound for cancer therapy. Despite promising preclinical results, further safety and efficacy evaluation of hesperidin and hesperetin as well as their nanoformulations in clinical trials is required to ascertain their potentials to be developed as clinically useful agents for BC treatment. Hesperetin, but not naringenin, increased NO releases from human umbilical vein endothelial cells in a dose-dependent manner. | |
| PubChem ID | 72281 | |
| Additional PMIDs | 17927510 33882812 27449398 25204891 26502889 18515333 27262800 33880358 24394652 18197618 22438130 21741436 8875554 9781306 20112299 34866972 | |
| Additional sources of information | NA | |
| Safety | Despite promising preclinical results, further safety and efficacy evaluation of hesperidin and hesperetin as well as their nanoformulations in clinical trials is required to ascertain their potentials to be developed as clinically useful agents for BC treatment. |