Targeted Delivery of Colloidal Silver for MCF-7 Breast Cancer Treatment

2020 ◽  
Vol 17 (7) ◽  
pp. 613-621
Author(s):  
Shweta Rajawat ◽  
Manzar M. Malik

Background: Amongst various cancer diseases, breast cancer is frequently diagnosed malignancy in women. Existing treatments are inadequate, painful and toxic. New ways of treatments need to be explored. Methods: The present work proposes preparation and targeted delivery of a formulation, F-1, for MCF-7 breast cancer treatment. The formulation, colloidal silver (0.76 ppm), was prepared by electrolytic deposition technique and multi surface coatings. Black tea extract (2.25%v/v) was used as a capping agent to tune the morphology of silver nanoparticle and potato extract (6.25%v/v) as a functionalizing agent for targeting MCF-7 breast cancer site. Results: Characterization results show highly pure spherical silver nanoparticles with an average particle size of 15nm. The shift of peaks in the FTIR spectra of formulation confirms the interaction between nanoparticles and extracts. The UV-visible peak was obtained at 525nm, a typical characteristic of silver nanoparticles. In-vivo anti-cancer study of formulation gave a moderate therapeutic effect in Non-Obese Diabetic Severe Combined Immune Deficiency (NOD-SCID) mice. Conclusion: It is observed that tumor volumes obtained in the case of Formulation-1 were moderately inhibited from days 5 to 9. However, one of the mice in the Formulation-1 group inhibited tumor volume to 1.52 cc similar to one of the mice of positive control group (Adriamycin 1.42cc).

2020 ◽  
Vol 21 (6) ◽  
Author(s):  
Nusrat Chowdhury ◽  
Shanzay Chaudhry ◽  
Nicholas Hall ◽  
George Olverson ◽  
Qian-Jin Zhang ◽  
...  

Nutrients ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 59 ◽  
Author(s):  
Paramita Basu ◽  
Elizabeth Meza ◽  
Michael Bergel ◽  
Camelia Maier

Estrogen receptor antagonists are effective in breast cancer treatment. However, the side effects of these treatments have led to a rise in searching for alternative therapies. The present study evaluated the estrogenic, antiestrogenic, and antiproliferative activities of Euphorbia bicolor (Euphorbiaceae), a plant native to south-central USA. Estrogenic and antiestrogenic activities of latex extract and its phytochemicals were evaluated with a steroid-regulated yeast system expressing the human estrogen receptor α and antiproliferative properties were assessed in the ER-positive MCF-7 and T47-D and triple-negative MDA-MB-231 and MDA-MB-469 breast carcinomas. Genistein and coumestrol identified in the latex extract induced higher estrogenic and antiestrogenic activities compared to diterpenes and flavonoids. The latex extract, resiniferatoxin (RTX) and rutin induced antiproliferative activities in all cell lines in a dose-dependent manner, but not in human normal primary dermal fibroblast cultures. A biphasic effect was observed with MDA-MB-468 breast carcinoma in which the latex extract at low concentrations increased and at high concentrations decreased cell proliferation. Treatments with latex extract in combination with RTX or rutin reduced even more the proliferation of MCF-7 breast carcinoma compared to the individual latex, RTX, and rutin treatments. E. bicolor latex phytochemicals could contribute to developing commercial therapeutic agents for breast cancer treatment.


2020 ◽  
Author(s):  
yongxia chen ◽  
yunlu jia ◽  
misha mao ◽  
Yifeng Gu ◽  
Chenpu Xu ◽  
...  

Abstract Background Adriamycin (ADM) is currently one of the most effective chemotherapeutic agents in breast cancer treatment. However, growing resistance to ADM can lead to treatment failure and poor outcome. The underlying molecular mechanisms in ADM resistance in breast cancer remains unclear. PLAC8 is reported as a novel highly-conserved protein and functions as an oncogene or tumor suppressor in various tumors. Methods Here, we analyzed the expression profile of PLAC8 in breast cancer tissues and breast cancer cell lines, and explored the correlation of PLAC8 expression levels with patients’ outcomes and ADM response. One ADM resistant MCF-7 breast cancer cell (MCF-7/ADM) and its parental cell was used as in vitro models to identify the underlying mechanism of PLAC8 and ADM resistance. Breast cancer cells were transfected with PLAC8 knockdown and overexpression vectors, and MTT and colony formation assays were performed to test the cell response to ADM. Then, we tested the effect of PLAC8 on autophagy pathway by flow cytometry and immunofluorescence analysis, and the change of main autophagy-correlated factors expressions: LC3 and p62. Next, combining treatment of autophagy inhibitor/inducer and PLAC8 downregulation/upregulation revealed the participation of PLAC8 in autophagy pathway to synergistically regulate ADM resistance in breast cancer. Results Here, higher PLAC8 expression was correlated with poorer outcome and aggressive phenotype in breast cancer, and breast cancer patients with higher PLAC8 expression showed potential ADM resistance. PLAC8 expression level was also significantly elevated in ADM resistant MCF-7 breast cancer cells (MCF-7/ADM), compared to parental MCF-7 cells. In vitro experiments further confirmed that PLAC8 inhibition by siRNA or enforced overexpression by infecting pcDNA3.1(C)-PLAC8 plasmid correspondingly decreased or increased the ADM resistance. Subsequently, we demonstrated that ectopic PLAC8 expression in MCF-7/ADM cell blocked the accumulation of the autophagy-associated protein LC3II, and resulted in cellular accumulation of p62. Rapamycin-triggered autophagy significantly increased cell response to ADM, while the autophagy inhibitor 3-MA enhanced ADM resistance. Actually, 3-MA and PLAC8 could synergistically enhance ADM resistance via blocking the autophagy process. Additionally, the downregulation of p62 by siRNA attenuated the activation of autophagy and PLAC8 expression in breast cancer cells. Conclusion Our findings suggest that PLAC8, through participation of p62, inhibits autophagy and consequently results in ADM resistance in breast cancer. PLAC8/p62/autophagy pathway may act as novel therapeutic targets in breast cancer treatment and has potential clinical application in overcoming ADM resistance.


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