Silymarin inhibits proliferation of human breast cancer cells via regulation of the MAPK signaling pathway and induction of apoptosis

Abstract

Silymarin is a purified mixture of four isomeric flavonoids extracted from the seeds and fruit of the milk thistle plant, Silybum marianus (L.). Silymarin exhibits a wide variety of biological effects and is commonly used in traditional medicine. Therefore, the anticancer effects of silymarin on human breast cancer cells were investigated to determine its pharmacological mechanisms in vitro and in vivo. The viability and proliferation of MDA-MB-231 and MCF-7 breast cancer cells were investigated using MTT and wound healing assays. Silymarin decreased the viability and proliferation of MDA-MB-231 and MCF-7 cells in a concentration-dependent manner. The number of apoptotic bodies, as shown by DAPI staining, was increased in a concentration-dependent manner, indicating that silymarin induces apoptosis. Additionally, changes in the expression levels of apoptosis-related proteins were demonstrated in human breast cancer cells using western blotting. Silymarin increased the levels of Bax, cleaved poly-ADP ribose polymerase, cleaved caspase-9 and phosphorylated (p-)JNK, and decreased the levels of Bcl-2, p-P38 and p-ERK1/2. Furthermore, the inhibitory effects of silymarin on MCF-7 tumor growth were investigated. In mice treated with silymarin for 3 weeks (25 and 50 mg/kg), MCF-7 tumor growth was inhibited without organ toxicity. In MCF-7 tumors, silymarin induced apoptosis and decreased p-ERK1/2 levels, as assessed using a TUNEL assay and immunohistochemistry. These results indicated that silymarin inhibited breast cancer cell proliferation both in vitro and in vivo by modulating the MAPK signaling pathway. Therefore, silymarin may potentially be used as a chemo-preventive or therapeutic agent.

ZDQ-0620, a Novel Phosphatidylinositol 3-Kinase Inhibitor, Inhibits Colorectal Carcinoma Cell Proliferation and Suppresses Angiogenesis by Attenuating PI3K/AKT/mTOR Pathway

“…Apoptosis plays an important role in the process of tumor proliferation and is a key mechanism to inhibit the growth of cancer cells ( 26 ). At the same time, the molecular mechanisms of apoptosis has also been confirmed to play an important role in the anti-tumor effect of PI3K/AKT/mTOR pathway ( 26 – 28 ), by activating various apoptotic signals or inhibiting survival signals ( 29 , 30 ). In this study, we demonstrated that ZDQ-0620 can induce the apoptosis of HCT-116 cells through G0/G1 cell-cycle arrest.…”

Function and Application of Flavonoids in the Breast Cancer

“…Flavonoids ( Figure 1 ) can modulate proliferation [ 5 , 39 , 41 , 42 , 43 , 44 ], invasion [ 45 , 46 ], and inflammatory signals through a variety of pathways associated with their qualities as antioxidants [ 24 , 47 ], estrogen agonists, or CYP1 (Cytochrome P450) inhibitors [ 39 ]. Flavonoids have also been found to influence inflammatory signaling via systems such as NF-кB (nuclear factor B), which regulates cell proliferation and survival [ 21 , 23 ].…”

“…Many flavonoids have been shown to have anticancer properties. In human breast cancer cells, certain flavonoids (isorhamnetin, genkwanin, acacetin, silymarin, eriocitrin, icariin, kaempferol, silibinin, apigenin, and luteolin) suppress cell growth and induce apoptosis, autophagy, or cell cycle arrest [ 5 , 20 , 38 , 43 , 44 , 48 , 49 ]. Table 1 shows the anticancer properties of introduced flavonoids.…”

Effects of Two Varieties and Fertilization Regimes on Growth, Fruit, and Silymarin Yield of Milk Thistle Crop

“…Milk thistle (Silybum marianum (L.) Gaertn.) is a well-known source of silymarin, which has anticancer [1], hepatoprotective, anti-inflammatory [2], anti-collagenase [3], immunomodulatory [4], and neuroprotective properties [5]. Due to its pharmaceutical properties, this species is an important medicinal plant and it is cultivated in many European countries such as Austria, Bulgaria, Czech Republic, Germany, and Poland [6][7][8].…”

“…Thus, the evaluation of milk thistle genotypes of Greek origin, which exhibit high productivity and quality (e.g., high silymarin content), under low input and high input conditions is important in order to select genotypes that could be included in breeding programs. In this context, the aims of this study were (1) to assess two milk thistle varieties in terms of productivity and quality (e.g., silymarin content), (2) to evaluate the impact of sheep manure and inorganic fertilizer on crop yield and quality, (3) to examine the interaction effects of variety and fertilization on fruit and silymarin yield of milk thistle crop.…”