Silymarin antiproliferative and apoptotic effects: Insights into its clinical impact in various types of cancer

Abstract

Silymarin is a complex extract isolated from the plant Silybum marianum, widely known for its prominent antioxidant and hepatoprotective effects, although increasing evidences have reported extraordinary antiproliferative and apoptotic abilities. As a result, several signaling pathways involved in cell cycle control, cell proliferation, and cell death have been deconvoluted as critical mechanisms. In this regard, cyclin and cyclin‐dependent pathways have been the most studied ones. Following that, apoptotic pathways, such as p53, Akt, STAT‐3, Ras, and caspases pathways, have been extensively studied, although other mechanisms involved in inflammation and angiogenesis have also been highlighted as silymarin‐likely targets in cancer therapy. Therefore, the main challenge of this review is to discuss the diverse molecular mechanisms for silymarin antiproliferative and apoptotic effects; most of them largely studied in various types of cancers so far. Clinical trials and combination therapies related to silymarin application in cancer prevention and treatment are presented as well.

Autophagy activated by silibinin contributes to glioma cell death via induction of oxidative stress-mediated BNIP3-dependent nuclear translocation of AIF

“…Thus, these studies revealed that autophagy also plays an important role in improving intracellular ROS levels. Accumulating evidences showed as well that oxidative stress was responsible for silibinin-induced death in various types of cancer cells 8,12,33 . Recent studies proved that activation of p53 is a primary pathway via which silibinin improved intracellular ROS levels.…”

“…1a ). It has been widely used to treat and prevent many types of hepatobiliary disorders including alcoholic liver disease, nonalcoholic fatty liver disease, and mushroom poisoning 12 , 13 . Moreover, silibinin not only exert potent inhibitory effect on various types of cancer cells, such as breast cancer cells, prostate cancer cells, and glioma cells 7 , 14 , 15 , but also sensitizes glioma cells to TMZ, TRAIL or arsenic trioxide treatment and prevents hepatocyte injury induced by chemotherapy agent cisplatin 16 – 19 .…”

Tackling of Renal Carcinogenesis in Wistar Rats by Silybum marianum Total Extract, Silymarin, and Silibinin via Modulation of Oxidative Stress, Apoptosis, Nrf2, PPARγ, NF‐κB, and PI3K/Akt Signaling Pathways

“…Silymarin (Sm) and silibinin (Sb) are investigated to exert strong antineoplastic effects in both in vitro and in vivo models of cancer, including cancers of the prostate, bladder, skin, colon, lung, breast, and kidney [35][36][37][38][39][40][41]. During Sm and Sb treatment, several mechanisms have been applied, such as DNA repair, cell cycle arrest, inhibition of growth and pro-liferation in addition to antiangiogenic effects, and blockage of invasion and metastasis [42,43].…”

Isolation and Characterization of a Flavonoid and a Neolignan from Silybum marianum: In‐vitro Cytotoxic Evaluation

“…[11] Previous studies reported that it possess anticancer potential against several cancers like lungs, prostate, breast, cervical, skin, gastric, bladder, leukemia, larynx, nasopharyngeal" hepatic, glioblastoma and malignant melanoma. [12] It interferes with the apoptotic proteins and expression of cell cycle regulators. Silybin and silymarin also regulate the rate of cell survival and apoptosis.…”