Silymarin and its active component silibinin act as novel therapeutic alternatives for salivary gland cancer by targeting the ERK1/2-Bim signaling cascade

Choi, Eui Yul; Oh, Sangnam; Jang, Boonsil; Yu, Hyun-Ju; Shin, Ji‐Ae; Cho, Nam-Pyo; Yang, In‐Hyoung; Won, Dong‐Hoon; Kwon, Hye-Jeong; Hong, Seong Doo; Cho, Sung‐Dae

doi:10.1007/s13402-017-0318-8

Cited by 26 publications

(15 citation statements)

References 51 publications

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“…Silibinin induced apoptosis in human choriocarcinoma cells [ 33 ]. The anti-cancer effects of SLM and silibinin on salivary gland cancer have also been reported by Choi et al (2017) [ 34 ]. Chen et al (2018) showed that taxifolin suppressed the proliferation of human osteosarcoma cells [ 35 ].…”

Section: Discussionsupporting

confidence: 57%

Effects of Silymarin-Loaded Nanoparticles on HT-29 Human Colon Cancer Cells

et al. 2018

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Background and objective: Previous studies have demonstrated the anti-cancer effects of silymarin (SLM). However, the low bioavailability of SLM has restricted its use. This study investigated the toxic effect of nanostructured SLM encapsulated in micelles (Nano-SLM) on the growth of the HT-29 human colon cancer cell line. Materials and methods: HT-29 cells were treated with 25 μM/mL of SLM or Nano-SLM for 48 h. MTT and colony formation assays were used to assess the cytotoxicity and proliferation of HT-29 cells, respectively. The cells were stained with annexin V/PI for assessment of apoptosis. Results: MTT assays revealed that Nano-SLM treatment was able to exert a more pronounced toxic effect on the HT-29 cells as compared to free SLM treatment (p < 0.01). In the Nano-SLM-treated cells, colony numbers were significantly reduced in comparison to the free SLM-treated cells (p < 0.01). Apoptotic and necrotic indexes of Nano-SLM-treated HT-29 cells were also significantly increased in comparison to those of the free SLM-treated cells (p < 0.01). The viability, proliferation and apoptosis of healthy cells (NIH-3T3 cells) were not changed in response to Nano-SLM or SLM. Conclusions: Our results indicate that Nano-SLM enhances the anti-cancer effects of SLM against human colon cancer cells.

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Section: Discussionsupporting

confidence: 57%

Effects of Silymarin-Loaded Nanoparticles on HT-29 Human Colon Cancer Cells

et al. 2018

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“…Our research group recently found naturally-derived chemicals such as silymarin, caffeic acid phenethyl ester, and oridonin have anticancer efficacies by inducing apoptosis of HNCCs. (21–23) Fisetin is also naturally derived compound that can be easily synthesized and has no toxicity to normal cells. (24) First, we demonstrated that fisetin reduced cell viability and induced apoptosis in four different HNCCs (HSC3, MC3, Ca9.22, and HN22).…”

Section: Discussionmentioning

confidence: 99%

Induction of sestrin 2 is associated with fisetin-mediated apoptosis in human head and neck cancer cell lines

Won

Chung

Shin

et al. 2019

J. Clin. Biochem. Nutr.

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Fisetin was reported to have an anti-proliferative and apoptotic activity as a novel anti-cancer agent in various cancer cell lines. However, the possible molecular targets for the anti-cancer effect of fisetin in human head and neck cancer (HNCC) have not yet been clarified. In this study, the influence of fisetin on the growth and apoptosis of HNCCs were examined. In HSC3 cells, fisetin treatment reduced the viability and induced apoptosis. Through the results from the screening of the expression profile of apoptosis-related genes, sestrin 2 (SESN2) was functionally involved in fisetin-mediated apoptosis showing the knockdown of SESN2 by siRNA clearly restored fisetin-induced apoptosis. In addition, fisetin reduced the protein expression levels of phospho-mTOR (p-mTOR) and Mcl-1, which are the downstream molecules of SESN2. It also induced PARP cleavage by inducing an increase in the expression levels of SESN2 together with reducing mTOR and Mcl-1 proteins in other three HNCCs (MC3, Ca9.22, and HN22). Taken together, our findings suggest that the anti-cancer effect of fisetin on HNCCs is associated with SESN2/mTOR/Mcl-1 signaling axis.

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“…In addition, silibinin is also found to display various biological activities including anti-oxidative, anti-proliferative, anti-bacterial, anti-fungal, neuro-protective, anti-leishmanial, anti-osteoclastic and anti-metastatic activities [310][311][312][313][314][315][316][317]. Previous studies have reported that silibinin exerts remarkable effects in numerous cancers such as renal, hepatocellular and pancreatic carcinoma, bladder, breast, colorectal, ovarian, lung, salivary gland, prostate and gastric cancers, through the induction of apoptosis, inhibition of tumor growth, metastasis and angiogenesis [318][319][320][321][322][323][324][325][326][327][328].…”

Section: Silibininmentioning

confidence: 99%

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

et al. 2019

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Numerous natural products originated from Chinese herbal medicine exhibit anti-cancer activities, including antiproliferative, pro-apoptotic, anti-metastatic, anti-angiogenic effects, as well as regulate autophagy, reverse multidrug resistance, balance immunity, and enhance chemotherapy in vitro and in vivo. To provide new insights into the critical path ahead, we systemically reviewed the most recent advances (reported since 2011) on the key compounds with anti-cancer effects derived from Chinese herbal medicine (curcumin, epigallocatechin gallate, berberine, artemisinin, ginsenoside Rg3, ursolic acid, silibinin, emodin, triptolide, cucurbitacin B, tanshinone I, oridonin, shikonin, gambogic acid, artesunate, wogonin, β-elemene, and cepharanthine) in scientific databases (PubMed, Web of Science, Medline, Scopus, and Clinical Trials). With a broader perspective, we focused on their recently discovered and/or investigated pharmacological effects, novel mechanism of action, relevant clinical studies, and their innovative applications in combined therapy and immunomodulation. In addition, the present review has extended to describe other promising compounds including dihydroartemisinin, ginsenoside Rh2, compound K, cucurbitacins D, E, I, tanshinone IIA and cryptotanshinone in view of their potentials in cancer therapy. Up to now, the evidence about the immunomodulatory effects and clinical trials of natural anti-cancer compounds from Chinese herbal medicine is very limited, and further research is needed to monitor their immunoregulatory effects and explore their mechanisms of action as modulators of immune checkpoints.

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Silymarin and its active component silibinin act as novel therapeutic alternatives for salivary gland cancer by targeting the ERK1/2-Bim signaling cascade

Abstract: Taken together, we conclude that ERK1/2 signaling pathway inhibition by silymarin and silibinin increases the expression of the pro-apoptotic Bcl-2 family member Bim which, subsequently, induces mitochondria-mediated apoptosis in salivary gland cancer-derived cells.

Cited by 26 publications

References 51 publications

Effects of Silymarin-Loaded Nanoparticles on HT-29 Human Colon Cancer Cells

Effects of Silymarin-Loaded Nanoparticles on HT-29 Human Colon Cancer Cells

Induction of sestrin 2 is associated with fisetin-mediated apoptosis in human head and neck cancer cell lines

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

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