Unprecedented anticancer activities of organorhenium sulfonato and carboxylato complexes against hormone-dependent MCF-7 and hormone-independent triple-negative MDA-MB-231 breast cancer cells

Wilder, Paul T.; Weber, David J.; Winstead, Angela; Parnell, Sabreea J.; Hinton, Tiara V.; Stevenson, Monet; Giri, Dipak K.; Azemati, Samira; Olczak, Pola; Powell, Brent V.; Odebode, Tijesunimi; Tadesse, Solomon; Zhang, Yongchao; Pramanik, Saroj K.; Wachira, James; Ghimire, Sujan; McCarthy, Pumtiwitt C.; Barfield, Alexis; Banerjee, Hirendra Nath; Chen, Chao; Golen, James A.; Rheingold, Arnold L.; Krause, Jeanette A.; Ho, Douglas M.; Zavalij, Peter Y.; Shaw, Roosevelt; Mandal, Santosh K.

doi:10.1007/s11010-017-3181-z

Cited by 31 publications

(22 citation statements)

References 25 publications

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“…1. This study is designed to investigate the cell killing efficacy of PDT using our actively targeted nanoformulation (PLGA-PEG hTf BPD, referred to as "ANP") and compare it to both BPD in its free form (referred to as "free BPD") and passively targeted (PLGA-PEG BPD or "PNP") nanoparticles on TNBC cell line MDA-MB-231 (34)(35)(36)(37)(38)(39).…”

Section: Introductionmentioning

confidence: 99%

Remotely Phototriggered, Transferrin‐Targeted Polymeric Nanoparticles for the Treatment of Breast Cancer

Jadia

Kydd

Rai

2018

Photochem & Photobiology

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Triple-negative breast cancer (TNBC) has the worst prognosis among all subtypes of breast cancer. Currently, no targeted treatment has been approved for TNBC. The goal of this study was to design a remotely triggered, targeted therapy for TNBC using polymeric nanoparticles and light. Active targeting of TNBC was achieved by conjugating the nanoparticles to a peptide (hTf) that binds to the transferrin receptor, which is overexpressed in TNBC. Photodynamic therapy (PDT) was explored for TNBC treatment by remotely triggering benzoporphyrin derivative monoacid (BPD), a photosensitizer, using near-infrared light. In this study, we investigated the use of actively targeting polymeric nanoparticles for PDT against TNBC using in vitro imaging and cytotoxicity studies. Fluorescence imaging confirmed that the BPD-loaded nanoparticles showed greater fluorescence in TNBC cells compared to free BPD, but more importantly, actively targeted nanoparticles displayed stronger fluorescence compared to passively targeted nanoparticles. Moreover, fluorescence imaging following competition with empty targeted nanoparticles validated the specificity of the targeted nanoparticles for TNBC cells. The PDT killing results were in line with the fluorescence imaging results, where actively targeting nanoparticles exhibited the highest phototriggered cytotoxicity in TNBC cells, making them an attractive nanoplatform for TNBC treatment.

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Section: Introductionmentioning

confidence: 99%

Remotely Phototriggered, Transferrin‐Targeted Polymeric Nanoparticles for the Treatment of Breast Cancer

Jadia

Kydd

Rai

2018

Photochem & Photobiology

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“…To our knowledge, a direct comparative results showing the difference in curcumin efficiency between non-malignant and cancer cells using folate decorated liposomes has not been demonstrated thus far. To test this comparison in vitro and challenge the selective attribute of curcumin when encapsulated in a targeted liposomal modality, we decided to conduct a parallel study using non-malignant mammary epithelial cells, MCF-12A, and triple negative breast cancer cells (TNBC), MDA-MB-231 [51,[59][60][61][62][63].…”

Section: Ivyspringmentioning

confidence: 99%

Liposomes Aid Curcumin's Combat with Cancer in a Breast Tumor Model

Jadia¹,

Kydd²,

Piel³

et al. 2018

Oncomedicine

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Curcumin (CUR), a natural compound, has multiple antineoplastic properties and specificity toward tumor cells, however its bioavailability and water solubility are poor. Liposomes increase the therapeutic index of CUR by protecting the drug from enzymatic degradation and can be made long circulating by surface modification with polyethylene glycol (PEG). Folate receptor α (FRα) is overexpressed in several types of cancer. Therefore, a folate-conjugated liposomal CUR nanoconstruct can enhance tumor targeted drug therapy. In this study, we synthesized, characterized and tested the cytotoxicity of CUR loaded liposomes (folate modified and non-folate modified) and CUR free drug in non-malignant breast epithelial cells and breast cancer cells, in addition to assessing the effects of CUR on cell cycle. The breast cancer cells not only had increased uptake of liposomes compared to non-malignant cells, but also more showed greater cytotoxicity resulted from treatments with free CUR and liposomal CUR (folate surface-modified and non-folate liposome types). The imaging and killing results, indicated that the liposomal CUR formulations do not alter the therapeutic efficacy and selectivity of CUR to provide anticancer benefits. Moreover, the differences in cellular uptake between the two liposomal nanoconstructs were studied using flow cytometry which showed targeting of folate surface-modified liposomes in cancer cells based on the findings presented.

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“…Organometallic rhenium compounds are strong anticancer agents. Sometimes the IC 50 values of many organometallic rhenium compounds against numerous cancer cells have been found to be in nM ranges [ 5 ]. We and others have demonstrated that organometallic rhenium compounds are not active on normal cells [ 5 - 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…Sometimes the IC 50 values of many organometallic rhenium compounds against numerous cancer cells have been found to be in nM ranges [ 5 ]. We and others have demonstrated that organometallic rhenium compounds are not active on normal cells [ 5 - 8 ]. Many rhenium compounds have been found to be highly active on cancer cells resistant to chemo drugs [ 7 - 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…Although scores of similar organometallic rhenium complexes are now known [ 15 ], examples of the cytotoxic activity of these compounds on glioblastoma are scarce. We have recently synthesized a series of organometallic rhenium complexes (ASP-G) bearing the polypyridyl ligands, N ︵ N [ 5 ]. A scaffold for ASP-G is shown in Scheme II .…”

Section: Introductionmentioning

confidence: 99%

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The Effects of Synthesized Rhenium Acetylsalicylate Compounds on Human Astrocytoma Cell Lines

Banerjee¹,

Vaughan²,

Boston³

et al. 2018

J Cancer Sci Ther

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PurposeBecause of the scarcity of suitable brain cancer drugs, researchers are frantically trying to discover novel and highly potent drugs free of side effects and drug-resistance. Rhenium compounds are known to be nontoxic and exhibit no drug resistance. For that reason, we have developed a series of novel rhenium acetylsalicylato (RAC or ASP) complexes to test their cytotoxicity on brain cancer cells. Also we have attempted to explore the DNAbinding properties of these compounds because many drugs either directly or indirectly bind to DNA.MethodsWe have treated the RAC series compounds on human astrocytoma brain cancer cell lines and rat normal brain astrocyte cells and determined the efficacy of these complexes through in vitro cytotoxicity assay. We carried out the DNA-binding study through UV titrations of a RAC compound with DNA. Also we attempted to determine the planarity of the polypyridyl ligands of the RAC series compounds using DFT calculations.ResultsRAC6 is more potent than any other RAC series compounds on HTB-12 human astrocytoma cancer cells as well as on Glioblastoma Multiforme D54 cell lines. In fact, The IC-50 value of RAC6 on HTB-12 cancer cells is approximately 2 μM. As expected, the RAC series compounds were not active on normal cells. The DFT calculations on the RAC series compounds were done and suggest that the polypyridyl ligands in the complexes are planar. The UV-titrations of RAC9 with DNA were carried out. It suggests that RAC9 and possibly all RAC series compounds bind to minor grooves of the DNA.ConclusionBecause of the very low activity of RAC6 on normal cells and low lC50 value of on astrocytoma (HTB-12) cell lines, it is possible that RAC6 and its derivatives may potentially find application in the treatment of brain cancers. The DFT calculations and UV titrations suggest that RAC series compounds either bind to DNA intercalatively or minor grooves of the DNA or both. However, it is highly premature to make any definite statement in the absence of other techniques.

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Unprecedented anticancer activities of organorhenium sulfonato and carboxylato complexes against hormone-dependent MCF-7 and hormone-independent triple-negative MDA-MB-231 breast cancer cells

Cited by 31 publications

References 25 publications

Remotely Phototriggered, Transferrin‐Targeted Polymeric Nanoparticles for the Treatment of Breast Cancer

Remotely Phototriggered, Transferrin‐Targeted Polymeric Nanoparticles for the Treatment of Breast Cancer

Liposomes Aid Curcumin's Combat with Cancer in a Breast Tumor Model

The Effects of Synthesized Rhenium Acetylsalicylate Compounds on Human Astrocytoma Cell Lines

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