Effects of harmaline on cell growth of human liver cancer through the p53/p21 and Fas/FasL signaling pathways

Xu, Bin; Li, Minpeng; Yuan, Yu; He, Jun; Hu, Sen; Pan, Meng; Lu, Shi-Feng; Liao, Ke; Zhuang, Ping; Zhou, Yifei; Zhu, Jinmin

doi:10.3892/ol.2017.7495

Cited by 11 publications

(18 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results presented here suggested that harmaline obstructs the growth of cancerous cells and resonates well with earlier studies from other groups. 63 , 64 …”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Discovery of Harmaline as a Potent Inhibitor of Sphingosine Kinase-1: A Chemopreventive Role in Lung Cancer

et al. 2020

View full text Add to dashboard Cite

The sphingosine kinase-1/sphingosine-1-phosphate pathway is linked with the cancer progression and survival of the chemotherapy-challenged cells. Sphingosine kinase-1 (SphK1) has emerged as an attractive drug target, but their inhibitors from natural sources are limited. In this study, we have chosen harmaline, one of the β-carboline alkaloids, and report its mechanism of binding to SphK1 and subsequent inhibition. Molecular docking combined with fluorescence binding studies revealed that harmaline binds to the substrate-binding pocket of SphK1 with an appreciable binding affinity and significantly inhibits the kinase activity of SphK1 with an IC 50 value in the micromolar range. The cytotoxic effect of harmaline on non-small-cell lung cancer cells by MTT assay was found to be higher for H1299 compared to A549. Harmaline induces apoptosis in non-small-cell lung carcinoma cells (H1299 and A549), possibly via the intrinsic pathway. Our findings suggest that harmaline could be implicated as a scaffold for designing potent anticancer molecules with SphK1 inhibitory potential.

show abstract

“…The results presented here suggested that harmaline obstructs the growth of cancerous cells and resonates well with earlier studies from other groups. 63 , 64 …”

Section: Resultsmentioning

confidence: 99%

“… 62 Harmaline exhibits potential anticancer activity in multiple cancer cell lines with a low risk of toxic side effects, as reported by previous studies. 63 , 64 All of these studies direct that harmaline possesses the potential for using it as a novel antioxidant and antitumor agent in anticancer therapy. 57 …”

Section: Introductionmentioning

confidence: 99%

Discovery of Harmaline as a Potent Inhibitor of Sphingosine Kinase-1: A Chemopreventive Role in Lung Cancer

et al. 2020

View full text Add to dashboard Cite

show abstract

“…At the molecular level SAHA treatment caused signi cant changes in proteins involved in both cell cycle and cell phenotype. p53 is plays an important role in many molecular processes including DNA transcription and repair, cell cycle, genomic stability, chromosome segregation, apoptosis, and angiogenesis [50]. p21 is a potent cyclin-dependent kinase inhibitor that can stabilize the interaction between cyclin-dependent kinase (CDK)-4/6 and cyclin D and promote the formation of cyclin D/CDK complexes.…”

Section: Discussionmentioning

confidence: 99%

Nanomicelles Potentiate HDAC Inhibitor Efficacy In Vitro.

Pisano

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background. Amphiphilic block copolymers used as nanomicelle drug carriers can effectively overcome poor drug solubility and specificity issues. Hence, these platforms have a broad applicability in cancer treatment. In this study, Pluronic F127 was used to fabricate nanomicelles containing the histone deacetylase inhibitor SAHA, which has an epigenetic-driven anti-cancer effect in several tumor types. SAHA loaded nanomicelles were prepared using a thin-film drying method and characterized for size, surface charge, drug content and drug release properties. Loaded particles were tested for in vitro activity and their effect on cell-cycle and markers of metastasis. Results. Following detailed particle characterization, cell proliferation experiments demonstrated that SAHA loaded nanomicelles more effectively inhibited the growth of HeLa and MCF-7 cell lines compared with free drug formulations. The 30nm SAHA containing nanoparticles were able to release up to 100% of the encapsulated drug over a 72h time window. Moreover, gene and protein expression analyses suggested that this effect was achieved through the regulation of p21 and p53 expression. SAHA was also shown to upregulate E-cadherin expression, potentially influencing tumor migration and metastasis.Conclusions. This study highlights the opportunity to exploit pluronic-based nanomicelles for the delivery of compounds that regulate epigenetic processes, thus inhibiting cancer development and progression.

show abstract

“…In addition, the increase of p21 has also been demonstrated to be induced by a variety of environmental genotoxic agents (including chemicals and toxins) . The cytotoxicity assay using human hepatocellular (HepG2) cells revealed that harmaline can activate the Fas/FasL signaling pathway to inhibit the cell viability and induce the apoptosis of HepG2 by increasing the expression of p53 , p21, caspase‐3, and caspase‐8 . Aflatoxin B1 can also induce the senescence and apoptosis of germ cells in mouse testis through the upregulation of p53 and p21 .…”

Section: Discussionmentioning

confidence: 99%

“…47,48 The cytotoxicity assay using human hepatocellular (HepG2) cells revealed that harmaline can activate the Fas/FasL signaling pathway to inhibit the cell viability and induce the apoptosis of HepG2 by increasing the expression of p53, p21, caspase-3, and caspase-8. 49 Aflatoxin B1 can also induce the senescence and apoptosis of germ cells in mouse testis through the upregulation of p53 and p21. 50 These results show that p21, as a downstream factor, can give rise to the downregulation of the cell cycle.…”

Section: Effect Of Pft-α On the Expression Of Apoptosisrelated Protmentioning

confidence: 99%

p53‐Dependent pathway and the opening of mPTP mediate the apoptosis of co‐cultured Sertoli‐germ cells induced by microcystin‐LR

Liu

Huang

et al. 2019

Environmental Toxicology

View full text Add to dashboard Cite

Microcystin‐LR (MC‐LR), a potent endotoxin, can induce reproductive toxicity. In order to investigate the role and mechanisms of apoptosis (p53‐dependent and mitochondrial pathways) of germ cells induced by MC‐LR, the co‐cultured primary Sertoli‐germ cells from Sprague‐Dawley rats were used for the experiments. Expression levels of proteins, genes, and mitochondrial membrane potential (MMP) were obtained after exposing co‐cultured Sertoli‐germ cells to MC‐LR with or without the addition of the p53 inhibitor, pifithrin‐α (PFT‐α), and MMP inhibitor, cyclosporin A (CsA). Results indicated that MC‐LR could activate p53‐dependent pathway‐associated proteins in Sertoli‐germ cells, leading to a decrease in MMP (indicating the opening of mitochondrial permeability transition pore [mPTP] and the release of Cytochrome‐c [Cyt‐c]) from the mitochondria into the cytoplasm and eventually the induction of apoptosis. PFT‐α inhibited the expression ofp53, ameliorated the MMP of the co‐cultured Sertoli‐germ cells, and prevented the release of Cyt‐c from the mitochondria into the cytoplasm, which reduces the occurrence of apoptosis. Similarly, the decreased release of Cyt‐c from the mitochondria into the cytoplasm and the declined level of apoptosis in Sertoli‐germ cells induced by MC‐LR were observed after the addition of CsA. These results indicated that the apoptosis of the co‐cultured Sertoli‐germ cells induced by MC‐LR was mediated by the p53‐dependent pathway, with the involvement of the opening of mPTP.

show abstract

Effects of harmaline on cell growth of human liver cancer through the p53/p21 and Fas/FasL signaling pathways

Cited by 11 publications

References 25 publications

Discovery of Harmaline as a Potent Inhibitor of Sphingosine Kinase-1: A Chemopreventive Role in Lung Cancer

Discovery of Harmaline as a Potent Inhibitor of Sphingosine Kinase-1: A Chemopreventive Role in Lung Cancer

Nanomicelles Potentiate HDAC Inhibitor Efficacy In Vitro.

p53‐Dependent pathway and the opening of mPTP mediate the apoptosis of co‐cultured Sertoli‐germ cells induced by microcystin‐LR

Contact Info

Product

Resources

About