| In vitro: |
| Anticancer Drugs. 2015 Jul;26(6):599-611. | | Isoflavone lupiwighteone induces cytotoxic, apoptotic, and antiangiogenic activities in DU-145 prostate cancer cells.[Pubmed: 25734831] | Lupiwighteone (Lup) is an isoflavone-type compound. It is distributed widely in wild-growing plants such as Glycyrrhiza glabra, Lupinus, and Lotus pedunculatus. On the basis of existing research, Lupiwighteone shows antioxidant and antimicrobial effects, but its antitumor activity has not been reported as yet.
METHODS AND RESULTS:
This study aimed to examine the antitumor activity of Lupiwighteone, explore its antitumor mechanism in a human prostate carcinoma cell line (DU-145), and evaluate its antiangiogenetic activity in the human umbilical vein endothelial cell line (HUVEC). The results showed that Lupiwighteone could inhibit the growth of DU-145 and HUVEC cells in a concentration-dependent and time-dependent manner by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Flow cytometry analysis indicated that Lupiwighteone could induce cell cycle arrest, cells apoptosis, mitochondrial membrane potential loss, and an increase in intracellular reactive oxygen species of DU-145 cells. Upregulation of Bax, cytochrome c, caspase-3, and PARP-1 protein expressions and downregulation of Bcl-2, procaspase-9, and p-Akt protein expressions were observed by western blot after the treatment of Lupiwighteone. Furthermore, the effects of Lupiwighteone on the cellular behavior of HUVECs were also investigated.
CONCLUSIONS:
Altogether, our data proved the anticancer and antiangiogenesis potential of Lupiwighteone. | | Food Chem Toxicol . 2020 Jan;135:110863. | | Lupiwighteone induces caspase-dependent and -independent apoptosis on human breast cancer cells via inhibiting PI3K/Akt/mTOR pathway[Pubmed: 31604113] | | Abstract
Breast cancer is one of the most common causes of mortality in women. Lupiwighteone has anticancer effects in prostate cancer cells and neuroblastoma cells. However, the molecular and cellular mechanisms of lupiwighteone effects on human breast cancer cells are not as well known. In the present study, we investigated the effects of lupiwighteone on the proliferation and apoptosis of two different human cancer cells; MCF-7, an estrogen receptor (ER)-positive human breast cancer cell, and MDA-MB-231, a triple negative human breast cancer cell. Lupiwighteone treatment decreased the viability of MCF-7 and MDA-MB-231 cells. Lupiwighteone treatment resulted in apoptotic cell death in breast cancer cells, which was characterized by DNA fragmentation, accumulation of apoptotic cells, and nuclear condensation. We also showed that treatment with lupiwighteone induced caspase-dependent apoptosis (up-regulation of caspase-3, -7, -8, -9, PARP, and Bax or down-regulation of Bid, Bcl-2), induction of caspase-independent apoptosis (up-regulation of AIF and Endo G on cytosol), and inhibition of the PI3K/Akt/mTOR signaling pathway (down-regulation of PI3K, p-Akt, and p-mTOR) in both MCF-7 and MDA-MB-231 cells. These results suggest that lupiwighteone induces caspase-dependent and -independent apoptosis in both breast cancer cell lines via inhibiting PI3K/Akt/mTOR pathway.
Keywords: Anticancer; Apoptosis; Breast cancer cells; Caspases; Lupiwighteone; Natural products. |
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