Dual Effects of Silibinin on Human Pancreatic Cancer Cells

Lee, Su-Mi; Lee, Gil-Woo; Park, Seon-Young; Joung, Hosouk; Park, Chang-Hwan; Cho, Eunae; Kim, Hyunsoo; Choi, Sung-Kyu; Rew, Jong Sun

doi:10.21203/rs.3.rs-130714/v1

Cited by 2 publications

(2 citation statements)

References 38 publications

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“…Silibinin increased exogenous p53 levels in normal ductal cells while reducing the expression of stemness-related genes. Furthermore, it increased Ki-67 levels in pancreatic cancer cells but decreased them in normal ductal cells ( Lee et al, 2020 ).…”

Section: Role Of Silibinin In Cancermentioning

confidence: 99%

A comprehensive evaluation of the therapeutic potential of silibinin: a ray of hope in cancer treatment

Ray,

Islam,

Islam

et al. 2024

Front. Pharmacol.

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Natural compounds hold promise in the search for cancer therapies due to their unique chemical structures and combinations that may effectively combat cancer while minimizing toxicity and side effects compared to conventional treatments. Silibinin, a natural lignan, has been found to possess strong anti-cancer activity against several types of human cancers based on emerging research. This study aims to provide an overview of the therapeutic potential of silibinin in the treatment and prevention of cancers. A comprehensive search was conducted using various internet databases such as PubMed, Google Scholar, and ScienceDirect to identify relevant research papers. Silibinin has been shown to exhibit anticancer activity against several types of cancers, including liver, lungs, breast, prostate, colorectal, skin, and bladder cancers. Its multifaceted mechanisms of action contribute to its therapeutic effects. Silibinin exerts antioxidant, anti-inflammatory, anti-proliferative, pro-apoptotic, anti-metastatic, and anti-angiogenic activities, making it a promising candidate for cancer therapy. One of the key mechanisms underlying the anticancer effects of silibinin is its ability to modulate multiple signaling pathways involved in cancer development and progression. It can inhibit the activation of various oncogenic pathways, including PI3K/Akt, NF-κB, Wnt/β-catenin, and MAPK pathways, thereby suppressing cancer cell proliferation, inducing cell cycle arrest, and promoting apoptosis. Silibinin possesses great potential as an effective treatment agent for cancer. The multifaceted mechanisms of action, favorable safety profile, and potential synergistic effects of silibinin with conventional therapies make it an attractive candidate for further investigation and development as a cancer treatment. However, more extensive clinical studies are necessary to fully establish the efficacy, optimal dosage, and long-term effects of silibinin in cancer treatment.

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Section: Role Of Silibinin In Cancermentioning

confidence: 99%

A comprehensive evaluation of the therapeutic potential of silibinin: a ray of hope in cancer treatment

Ray,

Islam,

Islam

et al. 2024

Front. Pharmacol.

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“…For example, in pancreatic cancer it promotes growth arrest and apoptosis (see Table 6) and decreases CD44 signaling. However, Lee et al 408 found that in addition to the antitumoral actions, silymarin also upregulated cancer stemness-related genes, namely TWIST1, Snail, and c-Jun. At the same time, it decreased p53 wild type and increased Ki-67 (a marker of proliferation).…”

Section: The Main Problems With Silymarinmentioning

confidence: 99%

Role of Silymarin in Cancer Treatment: Facts, Hypotheses, and Questions

Koltai¹,

Fliegel

2022

J Evid Based Complementary Altern Med

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The flavonoid silymarin extracted from the seeds of Sylibum marianum is a mixture of 6 flavolignan isomers. The 3 more important isomers are silybin (or silibinin), silydianin, and silychristin. Silybin is functionally the most active of these compounds. This group of flavonoids has been extensively studied and they have been used as hepato-protective substances for the mushroom Amanita phalloides intoxication and mainly chronic liver diseases such as alcoholic cirrhosis and nonalcoholic fatty liver. Hepatitis C progression is not, or slightly, modified by silymarin. Recently, it has also been proposed for SARS COVID-19 infection therapy. The biochemical and molecular mechanisms of action of these substances in cancer are subjects of ongoing research. Paradoxically, many of its identified actions such as antioxidant, promoter of ribosomal synthesis, and mitochondrial membrane stabilization, may seem protumoral at first sight, however, silymarin compounds have clear anticancer effects. Some of them are: decreasing migration through multiple targeting, decreasing hypoxia inducible factor-1α expression, inducing apoptosis in some malignant cells, and inhibiting promitotic signaling among others. Interestingly, the antitumoral activity of silymarin compounds is limited to malignant cells while the nonmalignant cells seem not to be affected. Furthermore, there is a long history of silymarin use in human diseases without toxicity after prolonged administration. The ample distribution and easy accessibility to milk thistle—the source of silymarin compounds, its over the counter availability, the fact that it is a weed, some controversial issues regarding bioavailability, and being a nutraceutical rather than a drug, has somehow led medical professionals to view its anticancer effects with skepticism. This is a fundamental reason why it never achieved bedside status in cancer treatment. However, in spite of all the antitumoral effects, silymarin actually has dual effects and in some cases such as pancreatic cancer it can promote stemness. This review deals with recent investigations to elucidate the molecular actions of this flavonoid in cancer, and to consider the possibility of repurposing it. Particular attention is dedicated to silymarin's dual role in cancer and to some controversies of its real effectiveness.

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Dual Effects of Silibinin on Human Pancreatic Cancer Cells

Cited by 2 publications

References 38 publications

A comprehensive evaluation of the therapeutic potential of silibinin: a ray of hope in cancer treatment

A comprehensive evaluation of the therapeutic potential of silibinin: a ray of hope in cancer treatment

Role of Silymarin in Cancer Treatment: Facts, Hypotheses, and Questions

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