A natural flavonoid lawsonaringenin induces cell cycle arrest and apoptosis in HT-29 colorectal cancer cells by targeting multiple signalling pathways

Abstract

Colorectal cancer is the third most common malignancy in the world having a high mortality rate. Flavonoids possess many biological activities including anti-cancer activity. lawsonaringenin (LSG) is a flavonoid isolated from leaves of Lawsonia alba Lam. The objective of this study was to demonstrate the anti-cancer potential of LSG in colorectal cancer for the first time. The HT-29 cells were treated with LSG or 5-fluoruracil, as a positive control, to determine its effect on cell cytotoxicity by a MTT cell proliferation assay, and cell cycle progression and apoptosis using flowcytometry. We also determined the mechanisms underlying LSG-mediated growth inhibition of HT-29 cells by by investigating the expression of key oncogenes and apoptosis genes using q-RT PCR and immunocytochemical analysis. The cell cytotoxicity data showed that the IC value of LSG was significantly less than the IC value of 5-FU (50 µM). The anti-proliferative effect of LSG was mediated by arresting cells in the S phase of the cell cycle which then led to the induction of apoptosis the q-RT PCR and immunocytochemical analysis showed that LSG reduced the expression of ß-catenin (non-phosphorylated) and its downstream signalling target c-Myc, whereas it increased the phosphorylation of ß-catenin. Furthermore, LSG also downregulated the expression of oncogene K-Ras and anti-apoptotic proteins, Bcl-2, and Bcl-xL. In conclusion, our data demonstrates that LSG exerted its anti-tumor activity by arresting the cell cycle in S phase, and by downregulating the expression of oncogenes including ß-catenin, c-Myc, K-Ras and anti-apoptosis proteins Bcl-2 and Bcl-xL. This study suggests a potential use of natural flavonoid, lawsonaringenin, to attenuate colorectal cancer growth; however, further pre-clinical/clinical studies are required to establish its role as a therapeutic agent.

Dietary hawthorn-leaves flavonoids improves ovarian function and liver lipid metabolism in aged breeder hens

“…Furthermore, apoptosis induced by senescence and oxidative stress in the ovary is bound to cause lower estrogen levels, thereby reducing the egg-laying performance of aged hens ( Manolagas, 2010 ). It is reported that flavonoids can increase the serum level of estrogen of old laying hen by alleviating the ovary apoptosis ( Anwar et al, 2018 ; Yang et al, 2018 ; Maues et al, 2019 ). The current study indicated that adding HF into the diet of aged breeder hens increased the serum levels of estrogen and alleviated the ovary apoptosis.…”

Effect of Ducrosia flabellifolia and Savignya parviflora Extracts on Inhibition of Human Colon and Prostate Cancer Cell Lines

“…Our results indicated both plant extracts were able to arrest the cell cycle at different phases (Figure 5). It is reported that flavonoids and phenols can arrest the cell cycle in different cancer cells [35][36][37]. The results indicated that both plant extracts under study can induce apoptosis as late apoptosis and arresting the cells in different cell cycle phases (Figures 3 and 4).…”

A Novel Systems Pharmacology Method to Investigate Molecular Mechanisms of Scutellaria barbata D. Don for Non-small Cell Lung Cancer

“…In the end, we obtained all 33 candidate components (Supplementary Table 1) (The structures of the compounds were derived from NCBI 9 ) of SBD. Thereinto, flavonoids compounds have been reported to demonstrate significant biologic activity including anti-inflammatory, inhibit tumor angiogenesis, and cell cycle arrest (Zhang L. et al, 2017; Anwar et al, 2018). Such as, apigenin (MOL001 OB = 33.6% DL = 0.25), baicalein (MOL070 0B = 44.6% DL = 0.21).…”