Cytotoxic activity of sunitinib and everolimus in Caki-1 renal cancer cells is accompanied by modulations in the expression of apoptosis-related microRNA clusters and BCL2 family genes

Papadopoulos, Emmanuel I.; Yousef, George M.; Scorilas, Andreas

doi:10.1016/j.biopha.2014.12.043

Cited by 25 publications

(21 citation statements)

References 47 publications

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“…Bcl-2 family of genes plays a critical role in the regulation of the apoptotic process initiated at the mitochondria [ 39 ] and governed the mitochondrial outer membrane permeabilization [ 40 ]. Given that FAA has been identified as inducers of apoptosis, we sought to detect the Bcl-2 mRNA level in MCF-7 and MDA-MB-231 after treatment with FAA.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxicity and Proapoptotic Effects of Allium atroviolaceum Flower Extract by Modulating Cell Cycle Arrest and Caspase‐Dependent and p53‐Independent Pathway in Breast Cancer Cell Lines

Khazaei

Hamid

Ramachandran

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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Breast cancer is the second leading cause of cancer death among women and despite significant advances in therapy, it remains a critical health problem worldwide. Allium atroviolaceum is an herbaceous plant, with limited information about the therapeutic capability. We aimed to study the anticancer effect of flower extract and the mechanisms of action in MCF-7 and MDA-MB-231. The extract inhibits the proliferation of the cells in a time- and dose-dependent manner. The underlying mechanism involved the stimulation of S and G2/M phase arrest in MCF-7 and S phase arrest in MDA-MB-231 associated with decreased level of Cdk1, in a p53-independent pathway. Furthermore, the extract induces apoptosis in both cell lines, as indicated by the percentage of sub-G0 population, the morphological changes observed by phase contrast and fluorescent microscopy, and increase in Annexin-V-positive cells. The apoptosis induction was related to downregulation of Bcl-2 and also likely to be caspase-dependent. Moreover, the combination of the extract and tamoxifen exhibits synergistic effect, suggesting that it can complement current chemotherapy. LC-MS analysis displayed 17 major compounds in the extract which might be responsible for the observed effects. Overall, this study demonstrates the potential applications of Allium atroviolaceum extract as an anticancer drug for breast cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Cytotoxicity and Proapoptotic Effects of Allium atroviolaceum Flower Extract by Modulating Cell Cycle Arrest and Caspase‐Dependent and p53‐Independent Pathway in Breast Cancer Cell Lines

Khazaei

Hamid

Ramachandran

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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“…Vasuclar co-option was also highlighted in other cancers [ 19 ]. Interestingly, current evidence also shows that TKI resistance is reversible [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Elucidating mechanisms of sunitinib resistance in renal cancer: an integrated pathological-molecular analysis

et al. 2017

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Upon sunitinib treatment of metastatic renal cell carcinoma patients eventually acquire resistance. Our aim was to investigate microRNAs behind sunitinib resistance.We developed an in vivo xenograft and an in vitro model and compared morphological, immunhistochemical, transcriptomical and miRNome data changes during sunitinib response and resistance by performing next-generation mRNA and miRNA sequencing. Complex bioinformatics (pathway, BioFunction and network) analysis were performed. Results were validated by in vitro functional assays.Our morphological, immunhistochemical, transcriptomical and miRNome data all pointed out that during sunitinib resistance tumor cells changed to migratory phenotype. We identified the downregulated miR-1 and miR-663a targeting FRAS1 (Fraser Extracellular Matrix Complex Subunit 1) and MDGA1 (MAM Domain Containing Glycosylphosphatidylinositol Anchor 1) in resistant tumors. We proved firstly miR-1-FRAS1 and miR-663a-MDGA1 interactions. We found that MDGA1 knockdown decreased renal cancer cell migration and proliferation similarly to restoration of levels of miR-1 and miR-663.Our results support the central role of cell migration as an adaptive mechanism to secure tumor survival behind sunitinib resistance. MDGA1, FRAS1 or the targeting miRNAs can be potential adjuvant therapeutic targets, through inhibition of cancer cell migration, thus eliminating the development of resistance and metastasis.

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“…Apoptosis is one of the primary targets for a majority of conventional anti-cancer drugs. These drugs are able to induce fatal intracellular damage, which often activates a downstream cascade of molecular events [2].…”

Section: Effects Of Hepaclin-4 On Hepatocellular Carcinoma (Hep G2) Imentioning

confidence: 99%

Effects of Hepaclin-4 on Hepatocellular Carcinoma (Hep G2)

Dalkh,

Naranbat,

Bayarsaikhan

et al. 2018

Cent. Asian j. Med. Sci.

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Objective: Liver cancer is the fifth most frequent cancer worldwide and is usually diagnosed at an advanced stage. Natural products play an important role in anticancer drug therapy because they are effective in treating specific characteristics of cancer while also effective at reducing side effects. However, the cytotoxicity and anti-proliferative effects of Scutellaria baicalensis Georgi, Saussurea amara L, Chiazospermum erectum (L) Bernh, Carthamus tinctorius L., remain unclear. Our research aims to investigate the anti-cancer properties of Hepaclin-4 (Hep-4) extracts from the above mentioned plants. Methods: To evaluate the in vitro cytotoxicity of Hep-4, an ethanol extract of Hep-4 (500, 250, 125, 100, 50, and 10 μg/mL)L, doxorubicin, and 5-fluorouracil (5-FU) were assessed against the Hep G2 hepatocarcinoma cell line by monitoring proliferation using the MTT assay method. Results:The results demonstrated growth inhibition of cells in both dose-and time-dependent manners. Hep-4 inhibited Hep G2 transformation in 45% and the comparative group, 5-FU, effects on 40% of it. Conclusion: Our findings suggest that Hep-4 extracts have the potential to be a potent cytotoxic agent against Hep G2 cells, as it has commendable anti-proliferative effects against hepatocarcinoma cell lines and can be considered an effective adjuvant therapeutic agent.

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Cytotoxic activity of sunitinib and everolimus in Caki-1 renal cancer cells is accompanied by modulations in the expression of apoptosis-related microRNA clusters and BCL2 family genes

Cited by 25 publications

References 47 publications

Cytotoxicity and Proapoptotic Effects of Allium atroviolaceum Flower Extract by Modulating Cell Cycle Arrest and Caspase‐Dependent and p53‐Independent Pathway in Breast Cancer Cell Lines

Cytotoxicity and Proapoptotic Effects of Allium atroviolaceum Flower Extract by Modulating Cell Cycle Arrest and Caspase‐Dependent and p53‐Independent Pathway in Breast Cancer Cell Lines

Elucidating mechanisms of sunitinib resistance in renal cancer: an integrated pathological-molecular analysis

Effects of Hepaclin-4 on Hepatocellular Carcinoma (Hep G2)

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