Silybin suppresses cell proliferation and induces apoptosis of multiple myeloma cells via the PI3K/Akt/mTOR signaling pathway

Feng, Nan; Luo, Jianmin; Guo, Xiaojun

doi:10.3892/mmr.2016.4887

Cited by 30 publications

(19 citation statements)

References 23 publications

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“…Previous reports have demonstrated that silibinin inhibits mTOR pathway in both renal cell carcinoma and multiple myeloma cells [ 45 – 47 ]. Here, we showed that silibinin inhibited the phosphorylation of mTOR, p70S6K, and 4E-BP1 in human glioblastoma cells.…”

Section: Discussionmentioning

confidence: 99%

Silibinin Induced Human Glioblastoma Cell Apoptosis Concomitant with Autophagy through Simultaneous Inhibition of mTOR and YAP

Bai

Tay

Guo

et al. 2018

BioMed Research International

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Silibinin, also known as silybin, is the major flavonolignan isolated from Silybum marianum. Although previous reports demonstrated that silibinin exhibits significant tumor suppressor activities in various cancers by promoting cell apoptosis, it was also shown to trigger autophagy to counteract apoptosis induced by exogenous stresses in several types of cells. However, there is no report to address the role of silibinin induced autophagy in human A172 and SR glioblastoma cells. Our study showed that silibinin treatment not only inhibited the metabolic activities of glioblastoma cells but also promoted their apoptosis through the regulation of caspase 3 and PARP-1 in concentration- and time-dependent manners. Meanwhile, silibinin induced autophagy through upregulation of microtubule-associated protein a light chain 3- (LC3-) II. And autophagy inhibition with chloroquine, a lysosomotropic agent, significantly enhanced silibinin induced glioblastoma cell apoptosis. Moreover, silibinin dose-dependently downregulated the phosphorylation levels of mTOR at Ser-2448, p70S6K at Thr-389, and 4E-BP1 at Thr-37/46. Furthermore, the expression of YAP, the downstream effector of Hippo signal pathway, was also suppressed by silibinin. These results suggested that silibinin induced glioblastoma cell apoptosis concomitant with autophagy which might be due to simultaneous inhibition of mTOR and YAP and silibinin induced autophagy exerted a protective role against cell apoptosis in both A172 and SR cells.

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Section: Discussionmentioning

confidence: 99%

Silibinin Induced Human Glioblastoma Cell Apoptosis Concomitant with Autophagy through Simultaneous Inhibition of mTOR and YAP

Bai

Tay

Guo

et al. 2018

BioMed Research International

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“…What’s more, further study showed that Silybum marianum was associated with a trend towards significant reductions in liver toxicity in children with ALL with liver toxicity [ 39 ]. In MM cells, silibinin has been demonstrated to be useful in the treatment of MM via inhibition of proliferation and an increase in apoptosis via inhibiting PI3K/Akt-mTOR signaling pathways [ 37 ]. These are emerging new ways of silibinin usage which may be promising therapeutic interventions for the treatment of β-TM, AML, ALCL, and MM.…”

Section: Discussionmentioning

confidence: 99%

“…Silibinin has, however, been demonstrated to exert anti-multiple myeloma efficacy. Silibinin inhibition of cellular proliferation and increased apoptosis via repression of PI3K/Akt-(mammalian target of rapamycin) mTOR signaling have been recently reported to occur in U266 MM cells [ 37 ].…”

Section: Acute Myeloid Leukemiamentioning

confidence: 99%

Silibinin: an old drug for hematological disorders

Zou

Zhang

et al. 2017

Oncotarget

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IntroductionSilibinin (silybin), a non-toxic natural polyphenolic flavonoid, is the principal and the most biologically active component of silymarin. It is efficient in the treatment of acute and chronic liver disorders caused by toxins, drug, alcohol, hepatitis, and gall bladder disorders. Further, in our previous studies, we explored the anti-cancer efficacy in common cancers, such as lung, prostatic, colon, breast, bladder, as well as, hepatocellular carcinoma. Interestingly, silibinin is still not solely limited to the treatment of these diseases. Recent research endeavors suggest that silibinin may function diversely and serve as a novel therapy for hematological disorders.Areas coveredIt discovered several interesting viewpoints in the widely studied mechanisms of silibinin in the hematological disorders.Expert commentaryIn this report, we review the up-to-date findings of more potency roles of silibinin in β-thalassemia (β-TM), acute myeloid leukemia (AML), anaplastic large cell lymphoma (ALCL) and multiple myelomas (MM) therapy and attempt to clarify the mechanisms underlying its effects. There are two viewpoints: First, The functional mechanisms of silibinin in AML cells via regulating cell differentiation to exert anti-cancer effect; Second, combination treatment strategy may be a good choice.

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“…Alterations of signaling pathways are important in the regulation of multiple cellular functions of lung cancer, including cell growth and proliferation (21)(22)(23)(24). A previous study by Zhu et al confirmed that the AKT signaling pathway is involved in the intrinsic apoptosis of non small-cell lung cancer cells (25).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of TM7SF4 inhibits cell proliferation and metastasis of A549 cells through regulating the PI3K/AKT/mTOR signaling pathway

Yang

Song

Wang

et al. 2017

Molecular Medicine Reports

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Lung cancer is one of the most common types of malignant tumor worldwide. The etiology of lung cancer is complex and, although significant progress has been made in previous investigations, the molecular mechanism responsible for lung cancer remains to be fully elucidated. In the present study, the association between lung cancer and transmembrane 7 superfamily member 4 (TM7SF4) was investigated. Reverse transcription‑quantitative polymerase chain reaction technology was used to detect the expression of TM7SF4, and it was expressed at a high level in lung cancer. Furthermore, by overexpressing and inhibiting the expression of TM7SF4, the present study compared cell proliferation and migration rates. It was confirmed that TM7SF4 promoted lung cancer cell proliferation and migration. TM7SF4 was also confirmed to promote cancer cell migration and invasion by modulating the activation of the phosphatidylinositol 3‑kinase/Akt pathway in the A549 cells. Correspondingly, the inhibition of TM7SF4 decreased the expression of proteins associated with AKT, whereas the overexpression of TM7SF4 promoted the expression of the relevant proteins. Therefore, the present study confirmed that TM7SF4 was involved in the progression of lung cancer via regulating the activation of AKT. These findings suggested that TM7SF4 may be involved in the progression of lung cancer and may be a novel therapeutic target for this disease.

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Silybin suppresses cell proliferation and induces apoptosis of multiple myeloma cells via the PI3K/Akt/mTOR signaling pathway

Cited by 30 publications

References 23 publications

Silibinin Induced Human Glioblastoma Cell Apoptosis Concomitant with Autophagy through Simultaneous Inhibition of mTOR and YAP

Silibinin Induced Human Glioblastoma Cell Apoptosis Concomitant with Autophagy through Simultaneous Inhibition of mTOR and YAP

Silibinin: an old drug for hematological disorders

Downregulation of TM7SF4 inhibits cell proliferation and metastasis of A549 cells through regulating the PI3K/AKT/mTOR signaling pathway

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