Betacyanins enhance vitexin-2-O-xyloside mediated inhibition of proliferation of T24 bladder cancer cells

Abstract

Betacyanins (BC) were purified from beetroot (Beta vulgaris var. rubra L.) and tested, alone or in combination with vitexin-2-O-xyloside (XVX) from Beta vulgaris var. cicla L., for their ability to reduce the proliferation rate in T24 bladder cancer cells. Combination of BC and XVX exhibited a synergistic effect concerning the inhibition of proliferation in T24 cancer cells at 24 and 48 h but not after 72 h of incubation. The induction of apoptosis was evidenced by means of fluorescence activated cell sorting (FACS) analysis, as well as through the increase in caspase 3 and 8 activities. Using RTqPCR experiments, it was shown that the combination of XVX + BC was able to enhance the expression levels of pro-apoptotic BAX and downregulate anti-apoptotic BIRC5 (survivin), as well as pro-survival CTNNB1 (β-catenin). The most evident effect of BC was the increase of the activity of caspase 8, leading to induction of extrinsic apoptosis. Moreover, XVX, BC and their combination showed no cytotoxic effect on normal human skin NCTC 2544 keratinocytes. These results demonstrated the efficacy and the mechanisms of the action of BC and XVX, extracted from edible plants, and suggested that a diet or a nutrition supplement, enriched with these bioactive molecules, could be used in the prevention of human bladder cancer.

Berberine displays antitumor activity in esophageal cancer cellsin vitro

“…Compounds derived from plants have been identified as an important source of anticancer therapies and have played a vital role in the prevention and treatment of cancer because of their availability and low toxicity when compared with chemotherapy[15,16]. A compound derived from an alkaloid-containing plant, berberine, has been shown to possess numerous anticancer activities in various cells by interfering with the multiple aspects of tumorigenesis and tumor progression[9-12].…”

C-Glycosyl Flavonoids fromBeta vulgarisCiclaand Betalains fromBeta vulgarisrubra: Antioxidant, Anticancer and Antiinflammatory Activities-A Review

“…In T24 bladder cancer cells, which are resistant to several anticancer drugs (Massari et al, 2015), due to over expression of the MDR (Shimada et al, 2011) and mutated TP53 gene (Savio et al, 2014), vitexin-2-Oxyloside showed a remarkable dose-response anticancer effect, with an IC 50 of 8.8 ± 0.8 μM. This effect was exerted through an activation of the intrinsic pathway of apoptosis and downregulation of the mRNA level of baculoviral inhibitor of apoptosis repeatcontaining 5 (BIRC5) (Scarpa et al, 2016), the gene that codifies for survivin, a member of the inhibitor of apoptosis proteins, which allow the survival of the cancer cells (Samali and Jager, 2014).…”

“…In T24 bladder cancer cells, BC displayed a dose–response antiproliferative effect, with an IC 50 of 99.8 ± 19.9 μg/mL, while the BX did not show any effect (Scarpa et al , ). Most of the studies in literature show that BC have a higher antitumor effect than BX (Clifford et al , ).…”

“…Regarding the reduction of the β‐catenin expression levels, other authors have shown that the sole reduction of CTNNB1 mRNA levels caused a considerable reduction in the proliferation rate of T24 bladder cancer cells (Yang et al , ). Therefore, the remarkable reduction in the expression levels of the pro‐survival gene CTNNB1, exerted by XVX + BC, very likely contributes to the reduction in the proliferation rate in T24 cancer cells (Scarpa et al , ).…”

“…Importantly, vitexin‐2‐O‐xyloside and BC, neither individually nor in combination, were able to exert cytotoxic effects on normal human skin NCTC 2544 keratinocytes (Scarpa et al , ), thus demonstrating that their cytotoxic and pro‐apoptotic effects specifically target the tumor cells.…”