Silymarin causes caspases activation and apoptosis in K562 leukemia cells through inactivation of Akt pathway

Zhong, Xian; Zhu, Yaping; Lu, Qinghua; Zhang, Jiawei; Ge, Zhen; Zheng, Shu

doi:10.1016/j.tox.2006.07.021

Cited by 34 publications

(26 citation statements)

References 30 publications

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“…Silibinin synergies the growth-inhibitory effect of mitoxantrone, a topoisomerase II inhibitor in prostate carcinoma PC-3 cells by reducing cell viability with increased apoptosis [34]. Silymarin causes apoptosis in human K562 leukemia cells by inhibiting Akt activity associated with activation of caspases-9 and -3 as well as PARP cleavage [35]. We have also shown apoptosis induction by silibinin involving p53-caspase 2 activation and caspase-mediated cleavage of Cip1/p21 in bladder transitionalcell papilloma RT4 cells [36].…”

Section: Induction Of Apoptosis By Silymarinmentioning

confidence: 99%

Multitargeted therapy of cancer by silymarin

2008

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Silymarin, a flavonolignan from milk thistle (Silybum marianum) plant, is used for the protection against various liver conditions in both clinical settings and experimental models. In this review, we summarize the recent investigations and mechanistic studies regarding possible molecular targets of silymarin for cancer prevention. Number of studies has established the cancer chemopreventive role of silymarin in both in vivo and in vitro models. Silymarin modulates imbalance between cell survival and apoptosis through interference with the expressions of cell cycle regulators and proteins involved in apoptosis. In addition, silymarin also showed anti-inflammatory as well as anti-metastatic activity. Further, the protective effects of silymarin and its major active constituent, silibinin, studied in various tissues, suggest a clinical application in cancer patients as an adjunct to estabilished therapies, to prevent or reduce chemotherapy as well as radiotherapy-induced toxicity. This review focuses on the chemistry and analogues of silymarin, multiple possible molecular mechanisms, in vitro as well as in vivo anticancer activities, and studies on human clinical trials.

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Section: Induction Of Apoptosis By Silymarinmentioning

confidence: 99%

Multitargeted therapy of cancer by silymarin

2008

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“…38 In contrast to silymarin, silibinin caused cell cycle arrest in the G1 phase in human colon carcinoma HT-29 cells and inhibited cell proliferation rate at concentrations of…”

Section: Discussionmentioning

confidence: 99%

“…Silymarin at concentrations of 24-48 lg/mL induced apoptotic death by inhibiting Akt activity 38 or the p53-dependent pathway, 39 decreasing cell viability by 40-20%. 38 In contrast to silymarin, silibinin caused cell cycle arrest in the G1 phase in human colon carcinoma HT-29 cells and inhibited cell proliferation rate at concentrations of…”

Section: Discussionmentioning

confidence: 99%

Increase of Phosphatase and Tensin Homolog by Silymarin to Inhibit Human Pharynx Squamous Cancer

Chen

Liao³

et al. 2013

Journal of Medicinal Food

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Silymarin is an active principle from the seeds of the milk thistle plant and is widely used as a hepatoprotective gent due to its antioxidant-like activity. In the present study, we evaluated the potential efficacy of silymarin against oral cancer and investigated its possible mechanism of action. Cell viability assay and western blotting analyses were used to identify silymarin-induced apoptotic cell death in human pharynx squamous cell carcinoma (FaDu) cells. The short interfering RNA (siRNA) is used to confirm the role of phosphatase and tensin homolog (PTEN) in silymarin-induced apoptosis. Treatment of FaDu cells with silymarin resulted in a significant decrease in cell viability (up to 70%). Silymarin inhibited the phosphorylation of Akt (over 10-fold) with an increase in expression of PTEN (five to sixfold). Consequently, the level of Bcl-2 expression was decreased five to sixfold and caspase 3 activated to induce apoptosis. Treatment with siRNA specific to PTEN gene diminished the action of silymarin. The results suggest that silymarin inhibits the Akt signaling pathway by increasing PTEN expression in FaDu cells and directly affects Bcl-2 family members. Also, we demonstrated the inhibitory activity of silymarin for oral cancer is related to cell survival. These mechanisms may in part explain the actions of silymarin and provide a rationale for the development of silymarin as an anticancer agent.

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“…Silymarin can help normal cells and tissues in case of damages through its anti-inflammatory [31], immunomodulatory, and antioxidant properties [21,22,23]. Also, silymarin showed the ability to inhibit tumor growth [32] and prevent metastasis [9,33]. In this report it has been documented that silymarin at 100 µmol/l induced apoptotic death through inhibition of Akt activity [32] or p53-dependent pathway [34] to result in an inhibition of cell viability [32] similar to cytotoxic effect.…”

Section: Discussionmentioning

confidence: 99%

Dual Effects of Silymarin on Nasopharyngeal Carcinoma Cells (NPC-TW01)

Chen

Liao

et al. 2013

Complement Med Res

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Background: Silymarin is an active component from the seeds of Silybum marianum and is widely used as a hepatic protection agent. Apoptosis induced by silymarin has been mentioned in cervical cancer cells. However, silymarin shows dual effects on tumor cells: cytostatic action at a low dose and cytotoxic action at higher dose. Thus, in the present study, we focused on low-dosing of silymarin in nasopharyngeal carcinoma cells, NPC-TW01 (TW01). Methods: Cell viability assay was used to screen the effect of silymarin in TW01 cells. Western blot analysis was used to identify the expressions of antioxidant enzymes and anti-/proapoptotic proteins. Fluorescent dyes are employed to detect the content of reactive oxygen species (ROS) and cell apoptosis. Results: Treatment of TW01 cells with silymarin at a low dose (80 µmol/l) resulted in a significant increase of antioxidant enzymes. Silymarin increased the expressions of superoxide dismutase 1, catalase, and glutathione peroxidase. Consequently, the cell apoptosis was reduced markedly. An increase of Bcl-2 expression and a decrease of activated caspase-3 or apoptosis-inducing factor (AIF) were observed in TW01 cells at a low dose (80 µmol/l) treatment. Conclusion: Silymarin at a low dose can induce cytostatic effect on TW01 cells mainly through an increase of antioxidant-like action. Thus, silymarin should be applied carefully to patients with nasopharyngeal carcinoma.

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Silymarin causes caspases activation and apoptosis in K562 leukemia cells through inactivation of Akt pathway

Cited by 34 publications

References 30 publications

Multitargeted therapy of cancer by silymarin

Multitargeted therapy of cancer by silymarin

Increase of Phosphatase and Tensin Homolog by Silymarin to Inhibit Human Pharynx Squamous Cancer

Dual Effects of Silymarin on Nasopharyngeal Carcinoma Cells (NPC-TW01)

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