Silymarin: A Promising Natural Extract in Cancer Treatment

The flavonoid silymarin extracted from the seeds of Sylibum marianum is a mixture of 6 flavolignan isomers out of which the 3 most important are silybin (or silibinin), silydianin, and silychristin. The standardized extract obtained from the dried seeds of Silybum marianum (milk thistle) contains approximately 70% to 80% of the silymarin complex and an approximately 20% to 30% chemically undefined fraction, comprising mostly other polyphenolic compounds. The main component is silybin (silibinin).

This group of flavonoids has been extensively studied and they have been used as hepato-protective substances in nonalcoholic fatty liver disease with favorable results; in the reduction or inhibition of hepatic fibrosis: silymarin showed the ability to reduce hepatic fibrosis in the early stages of liver injuries; and also in cirrhosis: silymarin decreased mortality in patients with hepatic cirrhosis.

The history of silymarin uses

There is a long history of silymarin use in human diseases without toxicity after prolonged administration:

Silymarin has been used in Europe since the fourth century BCE to treat serpent venom bites. It was also used in Ancient Egypt. Later on, during the Renaissance, some of the therapeutic effects were discovered and published. In the seventeenth century, an English botanist, Nicholas Culpeper, suggested that milk thistle was useful for liver diseases.

Recently, Silymarin has been proposed for the treatment of many different diseases such as Alzheimer’s dementia; SARS-2 Covid-19; diabetes and its complications; hyperlipidemia and hypercholesterolemia, etc. However, in the last 15 years, the main focus has been cancer prevention and treatment.

Silymarin in Cancer Treatment

Silymarin compounds have clear anticancer effects. Some of them are:

• decreasing migration through multiple targeting,
• decreasing hypoxia,
• inducing apoptosis in some malignant cells, and inhibiting promitotic signaling among others.

It is a unique virtue that the antitumoral activity of silymarin compounds is limited to malignant cells while the nonmalignant cells seem not to be affected.

Here are a few examples of recent findings on silymarin anticancer activity for different types of cancer:

• Melanoma: Silymarin decreased the growth of and inhibited tumor growth in vitro and in vivo and has been proposed for chemoprevention of melanoma.
• Prostate: Silibinin treatment caused growth inhibition, apoptosis, and decreased viability in different prostate cancer cell lines.
• Lung: Silibinin showed enhanced antitumor activity.
• Bladder: Silibinin reversed chemotherapeutic resistance in bladder cancer cells and decreased bladder cancer metastasis and prolonged animal survival.
• Pancreas: Silibinin-induced cell cycle arrest and apoptosis in certain pancreatic cancer cell lines.
• Breast: Silibinin synergized with conventional chemotherapeutic drugs in anticancer effects on breast cancer cells.
• Colon: Silibinin inhibited proliferation and increased apoptosis in colon cancer cells.
• Liver: Silibinin decreased cell proliferation and migration of human hepatocellular cancer cells.
• Ovary: Silibinin decreases tumor growth in vitro and in vivo.
• Hematologic: Silibinin-induced differentiation of acute myeloid leukemia cells and  Epstein-Barr positive lymphoma cell proliferation was inhibited.