The palladacycle, BTC2, exhibits anti-breast cancer and breast cancer stem cell activity

Kimani, Serah; Chakraborty, Suparna; Irene, Ikponmwosa; Mare, Jo‐Anne de la; Edkins, Adrienne L.; Toit, André du; Loos, Ben; Blanckenberg, Angelique; Niekerk, Anton van; Costa-Lotufo, Letı́cia V.; ArulJothi, K.N.; Mapolie, Selwyn F.; Prince, Sharon

doi:10.1016/j.bcp.2021.114598

Cited by 17 publications

(6 citation statements)

References 44 publications

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“…Cell cycle progression is a tightly regulated process that is essential for the growth and division of cells. Recent studies have suggested that inducing G2/M phase cell cycle arrest can lead to the inhibition of cell proliferation and the induction of apoptosis [ 63 , 64 ]. In our study, we also found that DHA treatment, alone or in combination with doxorubicin, arrested the cell cycle of MCF-7/Dox cells at the G2/M phase.…”

Section: Discussionmentioning

confidence: 99%

Docosahexaenoic Acid, a Key Compound for Enhancing Sensitization to Drug in Doxorubicin-Resistant MCF-7 Cell Line

et al. 2023

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Drug resistance is a well-known and significant obstacle in the battle against cancer, rendering chemotherapy treatments often ineffective. To improve the effectiveness of chemotherapy, researchers are exploring the use of natural molecules that can enhance its ability to kill cancer cells and limit their spread. Docosahexaenoic acid (DHA), a lipid found in marine fish, has been shown to enhance the cytotoxicity of various anti-cancer drugs in vitro and in vivo. While the combined use of chemotherapeutic drugs with DHA demonstrated promising preliminary results in clinical trials, there is still a significant amount of information to be discovered regarding the precise mechanism of action of DHA. As the biological pathways involved in the chemosensitization of already chemoresistant MCF-7 cells are still not entirely unraveled, in this study, we aimed to investigate whether DHA co-treatment could enhance the ability of the chemotherapy drug doxorubicin to inhibit the growth and invasion of MCF-7 breast cancer cells (MCF-7/Dox) that had become resistant to the drug. Upon treating MCF-7/Dox cells with DHA or DHA–doxorubicin, it was observed that the DHA–doxorubicin combination effectively enhanced cancer cell death by impeding in vitro propagation and invasive ability. In addition, it led to an increase in doxorubicin accumulation and triggered apoptosis by arresting the cell cycle at the G2/M phase. Other observed effects included a decrease in the multi-drug resistance (MDR) carrier P-glycoprotein (P-gp) and TG2, a tumor survival factor. Augmented quantities of molecules promoting apoptosis such as Bak1 and caspase-3 and enhanced lipid peroxidation were also detected. Our findings in the cell model suggest that DHA can be further investigated as a natural compound to be used alongside doxorubicin in the treatment of breast cancer that is unresponsive to chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Docosahexaenoic Acid, a Key Compound for Enhancing Sensitization to Drug in Doxorubicin-Resistant MCF-7 Cell Line

et al. 2023

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“…PTX increases the level of ROS in many types of cancer cells, including PTX-resistant cell lines (Mohiuddin and Kasahara 2021 ; Sugiyama et al 2020 ; Chen et al 2017 ). Phosphorylated γ-H2AX and CHK2 as sensitive indicators of DNA damage are commonly used to assess PTX-induced DNA damage or DNA replication stress (Kimani et al 2021 ; Gutiérrez-González et al 2013 ). In addition, altered microtubule dynamics, due to changes in the expression or post-translational modifications of microtubule-associated proteins (MAPs), may contribute to tumor resistance to PTX in a wide range of cancer types (Safinya et al 2016 ; Orr et al 2003 ; Xie et al 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Asparagus officinalis combined with paclitaxel exhibited synergistic anti-tumor activity in paclitaxel-sensitive and -resistant ovarian cancer cells

Zhang

Wang

Fan

et al. 2022

J Cancer Res Clin Oncol

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Purpose Although paclitaxel is a promising first-line chemotherapeutic drug for ovarian cancer, acquired resistance to paclitaxel is one of the leading causes of treatment failure, limiting its clinical application. Asparagus officinalis has been shown to have anti-tumorigenic effects on cell growth, apoptosis, cellular stress and invasion of various types of cancer cells and has also been shown to synergize with paclitaxel to inhibit cell proliferation in ovarian cancer. Methods Human ovarian cancer cell lines MES and its PTX-resistant counterpart MES-TP cell lines were used and were treated with Asparagus officinalis and paclitaxel alone as well as in combination. Cell proliferation, cellular stress, invasion and DMA damage were investigated and the synergistic effect of a combined therapy analyzed. Results In this study, we found that Asparagus officinalis combined with low-dose paclitaxel synergistically inhibited cell proliferation, induced cellular stress and apoptosis and reduced cell invasion in paclitaxel-sensitive and -resistant ovarian cancer cell lines. The combined treatment effects were dependent on DNA damage pathways and suppressing microtubule dynamics, and the AKT/mTOR pathway and microtubule-associated proteins regulated the inhibitory effect through different mechanisms in paclitaxel-sensitive and -resistant cells. Conclusion These findings suggest that the combination of Asparagus officinalis and paclitaxel have potential clinical implications for development as a novel ovarian cancer treatment strategy.

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“…The product was recrystallized by slow evaporation from an acetonitrile/dioxane solution to give colorless single crystals of dioxan solvate, [Zn( 2Me bpy) 3 ](ClO 4 ) 2 •1.5(dioxane), suitable for X-ray single crystal analysis. Yield: 0.69 g (79% /M -1 cm -1 ): 248 (27), 292 (41), and 304 (35).…”

Section: Instrumentationmentioning

confidence: 99%

Biological studies of a substituted bipyridine-coordinated Zn(II) ion: In vitro cytotoxicity, ROS-induced apoptosis, anti-metastatic and nuclease-like activity plus in silico binding affinity towards cancer-related proteins

Anjomshoa,

Sahihi,

Janczak

et al. 2023

Preprint

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A new dimethyl-substituted bipyridine-Zn(II) complex was synthesized and structurally characterized. Single-crystalline structure of the complex was successfully elucidated as [Zn(2Mebpy)3](ClO4)2•1.5(dioxane) by X-ray diffraction, where 2Mebpy represents 4,4′-dimethyl-2,2′-bipyridine. Also, the three-dimensional electrostatic potential maps (3D ESP) were plotted for [Zn(2Mebpy)3]2+ cation and [Zn(2Mebpy)3](ClO4)2 molecule. The in vitro cytotoxicity of the complex, compared with cisplatin, was evaluated towards the human breast (MCF-7) and glioblastoma (U-87MG) cancer cells as well as normal murine embryo cells (NIH/3T3). Noteworthily, great cytotoxicity and selectivity of the Zn(II) complex against MCF˗7 cells was confirmed by IC50 value of 5.1±0.5 μM and selectivity index of 3.2 over 48 h. The complex-induced MCF-7 and U-87 cells death mostly proceeded through an apoptotic pathway in a dose-dependent manner as evidenced by the flow cytometric results. The complex demonstrated potential anti-metastatic activity against MCF-7 cells as evidenced by inhibition of colony formation and cell migration. The apoptotic mechanism in the complex-treated MCF-7 cells was probably associated with the overproduction of reactive oxygen species (ROS). The comet assay results also showed that the complex could induce DNA damage in MCF-7 cells. Moreover, the complex exhibited hydrolytic cleavage of pUC19 DNA, which may be responsible for their observed cytotoxic effect to some extent. Finally, binding affinity of the complex towards cancer therapeutic targets such as anti-apoptotic proteins, estrogen receptor α, tubulin, and topoisomerase II was predicted by in silico molecular docking. In conclusion, the complex can be introduced as a potential therapeutic agent in breast cancer. This work indicate that other metal-cored complexes baring bypyridine derivatives can also exhibit promissing anticancer effects, opening the window towards a battery of similar candidate structures.

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The palladacycle, BTC2, exhibits anti-breast cancer and breast cancer stem cell activity

Cited by 17 publications

References 44 publications

Docosahexaenoic Acid, a Key Compound for Enhancing Sensitization to Drug in Doxorubicin-Resistant MCF-7 Cell Line

Docosahexaenoic Acid, a Key Compound for Enhancing Sensitization to Drug in Doxorubicin-Resistant MCF-7 Cell Line

Asparagus officinalis combined with paclitaxel exhibited synergistic anti-tumor activity in paclitaxel-sensitive and -resistant ovarian cancer cells

Biological studies of a substituted bipyridine-coordinated Zn(II) ion: In vitro cytotoxicity, ROS-induced apoptosis, anti-metastatic and nuclease-like activity plus in silico binding affinity towards cancer-related proteins

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