Cellular and molecular mechanisms of silibinin induces cell‐cycle arrest and apoptosis on HeLa cells

Zhang, Y.; Ge, Yakun; Chen, Y.; Li, Q.; Chen, J.; Dong, Ying; Shi, Wei

doi:10.1002/cbf.1842

Cited by 28 publications

(15 citation statements)

References 29 publications

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“…Moreover, other studies have also demonstrated that the anti-cancer mechanism of some agents was associated with cell cycle arrest and apoptosis induction. 16) Further, recent study have suggested that cell cycle destruction by exogenous agent was more promising effect rather than its apoptotic potential. 17) Furthermore, growing body of evidence provides evidence that morphine could inhibit various type of cancer cell growth, which were mostly regulated through inhibition of angiogenesis, 18) promoting apoptotic death via c-Jun N-terminal kinase (JNK)/caspase pathway 19) and modulating vascular endothelial growth factor (VEGF)-A expression, 20) which all leads to control tumor micro environment and metastasis.…”

Section: Discussionmentioning

confidence: 99%

Morphine Can Inhibit the Growth of Breast Cancer MCF-7 Cells by Arresting the Cell Cycle and Inducing Apoptosis

Chen

Qin

et al. 2017

Biological & Pharmaceutical Bulletin

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Morphine is widely used for relieving cancer pain in patients with advanced cancer. However, whether morphine can suppress or promote the progression of cancer in breast cancer patients receiving morphine analgesia remains unclear. Therefore, we used an in vitro model treated with morphine and naloxone to investigate the effects of morphine on breast cancer cell line MCF-7. MCF-7 cells were cultured with different concentrations (0.01 to 10 µM) of morphine at 12th, 24th, 36th, 48th, 60th and 72nd hours. Then, cell viability was measured through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell cycle and apoptosis assays were detected by flow cytometry (FCM). In addition, cell proliferation was conducted by colony formation assay. In this study, we have found that morphine (0.01 to 10 µM) could significantly reduce the cell vitality, growth and colony formation rate of MCF-7 cells, which has a certain relationship with cell cycle progression arrested at the G0/G1 and G2/M phase and MCF-7 cells apoptosis. Moreover, naloxone along with morphine could not reverse these effects, which indicates that the inhibition of MCF-7 breast cancer cell growth and proliferation by morphine could be its independent effect, not associated with opioid receptors. Morphine can inhibit cell growth by blocking the cell cycle and promote apoptosis in MCF-7 cells. Hence, morphine may be unable to promote the progression of cancer in breast cancer patients receiving morphine analgesia.Key words apoptosis; breast cancer; cell cycle; MCF-7 cell; morphine Breast cancer (BC) is the most commonly diagnosed cancer among women.1,2) In addition, younger women often present with more aggressive incidence of BC and leading to cause high mortality rate of BC, between the ages of 20 and 59. 3,4) Furthermore, most of the cancer patients are severely stressed by cancer pain, which in turn creates further psychological burden and affects patients outcome. Therefore, cancer pain has increasingly become the major focus of attention and opioids candidates are routinely used to treat cancer pain.Morphine is the representative opioid and is widely used for treatment in advanced cancer. 5,6) Besides, its analgesic action, morphine has anti-nociceptive effect, and might even change tumor progression. In our earlier study, we found that opioid molecule fentanyl could inhibit the vitality of gastric carcinoma cells and cell cycle progression, the mechanism of which might be associated with inhibition of nuclear factor-kappaB (NF-κB) nuclear translocation and phosphatase and tensin homolog deleted from chromosome 10 (PTEN) tumor suppressor gene upregulation. 7) We also demonstrated that morphine could suppress the growth and the cell cycle progression of MGC-803 cells, the mechanism of which might be related to activation of caspase-3 and caspase-9, and inhibition of NF-κB nuclear translocation. 8)Some studies have found that at a clinical concentration morphine (0.01 µM) can induce cell apoptosis or necrosis in MCF-7 human tu...

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Section: Discussionmentioning

confidence: 99%

Morphine Can Inhibit the Growth of Breast Cancer MCF-7 Cells by Arresting the Cell Cycle and Inducing Apoptosis

Chen

Qin

et al. 2017

Biological & Pharmaceutical Bulletin

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“…Silibinin exhibits anti-cancer activities mainly due to the cell cycle arrest [330,[338][339][340][341]. It induces G1 phase arrest in human pancreatic cancer SW1990 and AsPC-1, and breast cancer MCF-7 and MCF-10A cells [330,339,340], whilst it causes G2 phase arrest in human cervical cancer HeLa, and gastric cancer MGC-803 and SGC-7901 cells [338,341]. It also decreases the expressions of CDKs such as CDK1, CDK2, CDK4 and CDK6 that are involved in G1 and G2 progression [338,339].…”

Section: Silibininmentioning

confidence: 99%

“…It induces G1 phase arrest in human pancreatic cancer SW1990 and AsPC-1, and breast cancer MCF-7 and MCF-10A cells [330,339,340], whilst it causes G2 phase arrest in human cervical cancer HeLa, and gastric cancer MGC-803 and SGC-7901 cells [338,341]. It also decreases the expressions of CDKs such as CDK1, CDK2, CDK4 and CDK6 that are involved in G1 and G2 progression [338,339]. Besides, silibinin suppresses metastasis through ERK1/2 and MMP-9 down-regulation in human thyroid cancer TPC-1, breast cancer MCF-7, renal carcinoma ACHN, OS-RC-2 and SW-839, and epidermoid carcinoma A-431 cells [342][343][344].…”

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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“…Zhang et al [16] In vitro/cervical cancer Result of this study provides a strong rationale for future studies evaluating preventive and/or intervention strategies for silibinin in cervical cancer pre-clinical models Cell arrest in G2 phase, decrease in cyclin-dependent kinases involved in both G1 and G2 progression…”

Section: Cell-cycle Arrest Via Inhibition Of Cyclin-cdk Promoter Actimentioning

confidence: 95%

“…Rather, inhibition of cell cycle regulatory proteins plays a fundamental role in silibinin'smechanism of action, and this may serve as a basis for combined use with conventional chemotherapeutics. [6] The silibinin treatment of HeLa cells was found to arrest cells in G2 arrest and to induce a decrease in CDKs involved in both G1 and G2 progression in a study conducted by Zhang et al [16] In addition, silibinin also showed a dose-dependent and a time-dependent apoptotic death in HeLa cells in both the mitochondrial pathway and the death receptor-mediated pathway, providing a strong rationale for future studies evaluating preventive and/or intervention strategies for silibinin in cervical cancer pre-clinical models.…”

Section: Metabolism and Excretionmentioning

confidence: 98%

Silibinin: A promising anti-neoplastic agent for the future? A critical reappraisal

Chhabra¹,

Buzarbaruah²,

Singh

et al. 2013

Int J Nutr Pharmacol Neurol Dis

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Silibinin, a flavonolignan, is the major active component of the milk thistle plant (Silybummarianum). Silibinin have been used as medicinal herbs in the treatment of liver cirrhosis, chronic hepatitis, and gallbladder disorders. Numerous studies suggest that silibinin is a powerful antioxidant and has hepatoprotective properties and anti-neoplastic effects against various carcinoma cells. Silibinin had shown promising anti-neoplastic effects against skin, breast, lung, pancreatic, colon, cervical, prostate, bladder, and kidney carcinomas in various in vitro/in vivo and preclinical studies. Treatment claims also include lowering cholesterol levels, reducing insulin resistance, and anti-viral activity. Other reported uses of milk thistle in folk medicine include as a treatment for malarial fever, bronchitis, peritonitis, uterine congestion, varicose veins, and as a milk production stimulant for nursing mothers. The aim of the present article is to review and summarize the pharmacokinetics, physical properties, the mechanism of action, and the effectiveness and safety of silibininin various cancers/neoplasms.

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Cellular and molecular mechanisms of silibinin induces cell‐cycle arrest and apoptosis on HeLa cells

Cited by 28 publications

References 29 publications

Morphine Can Inhibit the Growth of Breast Cancer MCF-7 Cells by Arresting the Cell Cycle and Inducing Apoptosis

Morphine Can Inhibit the Growth of Breast Cancer MCF-7 Cells by Arresting the Cell Cycle and Inducing Apoptosis

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

Silibinin: A promising anti-neoplastic agent for the future? A critical reappraisal

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