Novel sulforaphane-enabled self-microemulsifying delivery systems (SFN-SMEDDS) of taxanes: Formulation development and in vitro cytotoxicity against breast cancer cells

Kamal, Mohammad Mostafa; Nazzal, Sami

doi:10.1016/j.ijpharm.2017.11.063

Cited by 40 publications

(9 citation statements)

References 62 publications

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“…Besides, PTX has poor water solubility and the solvents for injection might produce severe side-effects such as hypersensitivity, neutropenia myelosuppression, neutropenia, and neurotoxicity 49 , whereas SFN is a fat-soluble chemical, the combination of two drugs might promote formulations of non-injection administration of PTX via a SFN-enabled self-microemulsifying delivery system 50 . Except the ubiquitin-proteasome system activation, Caspase-3 cleavage might be an extra degrading way to cleave microtubule or its associated proteins.…”

Section: Discussionmentioning

confidence: 99%

Sulforaphane metabolites reduce resistance to paclitaxel via microtubule disruption

et al. 2018

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Long treatment with paclitaxel (PTX) might increase resistance and side-effects causing a failure in cancer chemotherapy. Here we uncovered that either sulforaphane-cysteine (SFN-Cys) or sulforaphane-N-acetyl-cysteine (SFN-NAC) induced apoptosis via phosphorylated ERK1/2-mediated upregulation of 26 S proteasome and Hsp70, and downregulation of βIII-tubulin, XIAP, Tau, Stathmin1 and α-tubulin causing microtubule disruption in human PTX-resistant non-small cell lung cancer (NSCLC) cells. Knockdown of either βIII-tubulin or α-tubulin via siRNA increased cell sensitivity to PTX, indicating that these two proteins help cells increase the resistance. Tissue microarray analysis showed that overexpression of βIII-tubulin correlated to NSCLC malignant grading. Immunofluorescence staining also showed that SFN metabolites induced a nest-like microtubule protein distribution with aggregation and disruption. Co-immunoprecipitation showed that SFN metabolites reduced the interaction between βIII-tubulin and Tau, and that between α-tubulin and XIAP. The combination of PTX with SFN metabolites decreased the resistance to PTX, and doses of both PTX and SFN metabolites, and enhanced apoptosis resulting from activated Caspase-3-caused microtubule degradation. Importantly, the effective dose of SFN metabolites combined with 20 nM PTX will be low to 4 μM. Thus, we might combine SFN metabolites with PTX for preclinical trial. Normally, more than 20 μM SFN metabolites only leading to apoptosis for SFN metabolites hindered their applications. These findings will help us develop a low-resistance and high-efficiency chemotherapy via PTX/SFN metabolites combination.

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Section: Discussionmentioning

confidence: 99%

Sulforaphane metabolites reduce resistance to paclitaxel via microtubule disruption

et al. 2018

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“…One of the most important ways for reducing or even inhibiting the side effects of sulforaphane is application of nanocarriers. A low concentration of sulforaphane can be loaded on nanocarriers, while its therapeutic impacts are at the highest level (Desai, Thakkar, Ann, Wang, & Prabhu, ; Kamal & Nazzal, ). More importantly, it appears that the beneficial effects of sulforaphane overweigh on its negligible harmful effects.…”

Section: Conclusion and Remarksmentioning

confidence: 99%

MicroRNAs as novel targets of sulforaphane in cancer therapy: The beginning of a new tale?

Rafiei

Ashrafizadeh

Ahmadi

2020

Phytotherapy Research

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Effective management and treatment of cancer depend on developing novel antitumor drugs with the capability of targeting various molecular pathways. Identification and subsequent targeting of these pathways are of importance in cancer therapy. MicroRNAs (miRNAs) are small noncoding RNA molecules responsible for post‐transcriptional regulation of genes. Notably, miRNAs participate in a number of biological processes such as proliferation, apoptosis, differentiation, and cell cycle regulation. So, any impairment in the expression and function of miRNAs is associated with development of disorders, particularly cancer. Naturally occurring nutraceutical compounds have attracted much attention due to their great antitumor activity. Among them, sulforaphane isolated from Brassica oleracea (broccoli) is of interest due to its therapeutic and biological activities such as antidiabetic, antioxidant, anti‐inflammatory, hepatoprotection, and cardiprotection. Sulforaphane has demonstrated great antitumor activity and is able to significantly inhibit proliferation, viability, migration, malignancy, and epithelial‐to‐mesenchymal transition of cancer cells. These antitumor effects have widely been investigated, and it appears that there is a need for a precise review to demonstrate the molecular pathway that sulforaphane follows to exert its antitumor activity. At the present review, we focus on the modulatory impact of sulforaphane on miRNAs and exhibit that how various miRNAs in different cancers are regulated by sulforaphane.

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“…These sophisticated systems can monitor cancer cell proliferation as well as distinguish cells undergoing apoptosis and necrosis (Xi et al, ). A recent study conducted by Kamal and Nazzal () have monitored live cell proliferation in sulforaphane–paclitaxel and sulforaphane–doxorubicin formulations treated MCF‐7 and MDA‐MB‐231 cells using the IncuCyte™ system. The Cell‐IQ platform has been used in a study conducted by Wang, Shi, et al () to monitor and record proliferation of human non‐small cell lung cancer (A549) upon treatment with a chemokine, CCL‐20.…”

Section: Cell Viability/cytotoxicity and Antiproliferative Assaysmentioning

confidence: 99%

In vitro assays and techniques utilized in anticancer drug discovery

Ediriweera

Tennekoon

Samarakoon

2018

J of Applied Toxicology

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Development of a cancer is a multistep process and six major hallmarks of cancer that are known to control malignant transformation have been described. Anticancer drug development is a tedious process, requiring a number of in vitro, in vivo and clinical studies. In vitro assays provide an initial platform for cancer drug discovery approaches. A wide range of in vitro assays/techniques have been developed to evaluate each hallmark feature of cancer and selection of a particular in vitro assay or technique mainly depends on the specific research question (s) to be examined. In the present review, we have described some commonly utilized in vitro assays and techniques used to examine cell viability/proliferation, apoptosis, cellular senescence, invasion and migration, oxidative stress and antioxidant effects, gene and protein expression, angiogenesis and genomic alterations in cancer drug discovery. Additionally, uses of modern techniques such as high throughput screening, high content screening and reporter gene assays in cancer drug discovery have also been described.

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Novel sulforaphane-enabled self-microemulsifying delivery systems (SFN-SMEDDS) of taxanes: Formulation development and in vitro cytotoxicity against breast cancer cells

Cited by 40 publications

References 62 publications

Sulforaphane metabolites reduce resistance to paclitaxel via microtubule disruption

Sulforaphane metabolites reduce resistance to paclitaxel via microtubule disruption

MicroRNAs as novel targets of sulforaphane in cancer therapy: The beginning of a new tale?

In vitro assays and techniques utilized in anticancer drug discovery

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