Matrine Inhibits Breast Cancer Growth ViamiR-21/PTEN/AktPathway in MCF-7 Cells

Abstract

Background: Matrine is one of the major alkaloids extracted from Sophora flavescens and has been used clinically for breast cancer with notable therapeutic efficacy in China. However, the mechanisms are still largely unknown. Methods: Cell viability was analyzed by MTT assay. After MCF-7 cells were treated with matrine for 48h, apoptosis was detected by flow cytometry, TUNEL assay and transmission electron microscopy, and the cell cycle distribution was also analyzed by flow cytometry. Further, the expression of PTEN, pAkt, Akt, pBad, Bad, p21^/WAF1/CIP1 , and p27^/KIP1 was determined by Western blot. Changes of miR-21 level were quantified by real-time RT-PCR. After miR-21 was transfected in MCF-7 cells, PTEN protein level was measured by Western blot. Results: Matrine inhibited MCF-7 cell growth in a concentration-and time-dependent manner, by inducing apoptosis and cell cycle arrest at G₁/S phase. Matrine up-regulated PTEN by downregulating miR-21 which in turn dephosphorylated Akt, resulting in accumulation of Bad, p21^/WAF1/CIP1 and p27^/KIP1. Conclusion: Our study unraveled, for the first time, the ability of matrine to suppress breast cancer growth and elucidated the miR-21/PTEN/Akt pathway as a signaling mechanism for the anti-cancer action of matrine. Our findings also reinforce the notion that miRNAs can act as mediators of the therapeutic efficacy of natural medicines.

Matrine improved the function of heart failure in rats via inhibiting apoptosis and blocking β3-adrenoreceptor/endothelial nitric oxide synthase pathway

“…Numerous studies have demonstrated that matrine possesses numerous biological activities, including antitumor, antivirus, antioxidant and anti-inflammatory actions (3,(6)(7)(8)12). However, the effects of matrine on heart failure have not previously been elucidated.…”

“…Matrine is able to inhibit cell proliferation and induce the apoptosis of acute myeloid leukemia cells via the mitochondrial pathway and Akt inactivation (7). Furthermore, the growth of MCF-7 breast cancer cells was also inhibited by matrine via the miR-21/PTEN/Akt pathway (8). Additionally, matrine exhibited antinociceptive effects on neuropathic pain induced by chronic constriction injury in mice (9).…”

Anti-tumor activities of active ingredients in Compound Kushen Injection

“…Matrine might repress the expression of miR-21, which can target and down-regulate the tumor suppressor PTEN. The upregulation of PTEN dephosphorylates Akt, resulting in an accumulation of Bad, p21/WAF1/CIP1 and p27/KIP1, which trigger intrinsic apoptotic cascades [13] . Matrine can also inhibit cell proliferation and induce apoptosis in a dose-and time-dependent manner in gastric carcinoma cells (SGC-7901).…”

Matrine induction of reactive oxygen species activates p38 leading to caspase-dependent cell apoptosis in non-small cell lung cancer cells

“…It has been found that matrine possesses a wide range of pharmacological activities, and its antitumor activity has attracted considerable attention in recent years. Cumulative data have demonstrated that matrine exerts anticancer effect on many series of human cancer cells including lung cancer (16), hepatoma (16), breast cancer (17), pancreatic cancer (18), prostate cancer (19,20) and colon cancer (21). Upregulation of protein E2F-1 and activation of caspases contribute to matrine-induced leukemia cell proliferation inhibition and apoptosis (15).…”