Triticuside A, a Dietary Flavonoid, Inhibits Proliferation of Human Breast Cancer Cells Via Inducing Apoptosis

Abstract

In this study we demonstrated that Triticuside A, one of the flavonoid compounds isolated from wheat bran, induced apoptosis and inhibited proliferation of human breast cancer cells. Triticuside A inhibited the proliferation of human breast cancer cells (MCF-7 and MDA-MB-231) in a dose-dependent manner but barely showed cytotoxicity to the normal human fibroblasts. Triticuside A-induced apoptosis was accompanied by a significant decrease of Mcl-1 and Bcl-2 proteins and by an increase of cleavage of caspases-3, -7, -9, and PARP. Triticuside A also suppressed the level of phospho-Akt and its downstream targets, mTOR and P70 S6 kinase. LY294002, a specific inhibitor of PI3K, significantly enhanced the Triticuside A-induced apoptosis. Moreover LY294002 not only downregulated the level of phospho-Akt but also enhanced the inhibition of Mcl-1 expression when combined with Triticuside A. Our results demonstrate for the first time the specific apoptogenic activity of Triticuside A in tumor cells and involvement of the mitochondrial apoptosis pathway and Akt/mTOR signaling pathway. Thus, Triticuside A may be a potentially useful wheat bran component that can be used for prevention or treatment of breast cancer.

Amplexicaule A exerts anti-tumor effects by inducing apoptosis in human breast cancer

“…The mitochondrial apoptosis pathway is an important means of inducing cell death, and flavonoids have been reported to activate mitochondrial apoptotic signaling [ 14 , 28 , 29 ]. As critical inhibitors of the mitochondrial apoptotic pathway [ 30 ], BCL-2 family proteins bind to the outer membrane of mitochondria and prevent release of cytochrome c [ 31 ].…”

“…Moreover, our data demonstrate that APA inhibits Akt/mTOR and P70 S6k in breast cancer cells. Flavonoids-induced Akt/mTOR inactivation is also reportedly responsible for suppression of BCL-2 and MCL-1 [ 14 , 37 ]. We hypothesize that APA-induced inactivation of Akt/mTOR pathways is responsible for the downregulation of BCL-2 and MCL-1 in the treated cells, which triggers apoptosis.…”

“…TCM therapies are often multiple components, multiple targets and multiple activities, like the combination chemotherapies used in cancer treatment [ 6 – 8 ]. For example, flavonoids exhibit antioxidant, anti-inflammatory and anti-cancer properties [ 9 – 12 ] in several human cancers [ 13 , 14 ]. The tumor suppressive effects of flavonoids are mediated through the induction of apoptosis and cell cycle arrest that results from interference with key intracellular signaling pathways [ 15 , 16 ].…”

Whole Grain Consumption for the Prevention and Treatment of Breast Cancer

“…Currently, there have been no direct studies conducted to evaluate the effect of grain-originated ARs on breast cancer, yet the effect is predictable. Besides ARs, triticuside A, a flavone C-glycoside from wheat bran, strongly suppressed the proliferation of human breast cancer cells (MCF-7 and MDA-MB-231) via the mitochondrial apoptosis pathway and the Akt/mTOR signaling pathway [95].…”

Quantitative Relationships Between the Cytotoxicity of Flavonoids on the Human Breast Cancer Stem‐Like Cells MCF7‐SC and Their Structural Properties

“…Therefore, measuring cell viability is a commonly used method to screen potential new chemotherapeutic agents. Many flavonoids have been demonstrated to show cytotoxicity against cancer cells including breast cancer cells . The cytotoxic properties of flavonoids are likely attributed to their effects on inhibiting cell cycle progression and/or triggering apoptosis .…”