Synergistic Antiproliferative Effects of Co-nanoencapsulated Curcumin and Chrysin on MDA-MB-231 Breast Cancer Cells Through Upregulating miR-132 and miR-502c

Javan, Naser; Ansari, Mohammad Hassan Khadem; Dadashpour, Mehdi; Khojastehfard, Mehran; Bastami, Milad; Rahmati-Yamchi, Mohammad

doi:10.1080/01635581.2019.1599968

Cited by 45 publications

(22 citation statements)

References 56 publications

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“…Figure S11, SI). The induction of apoptotic cell death by curcumin has been found in many different breast cancer [60,61], gastric [62] and lung cancer cell lines [63], and has also been reported for HeLa [64], T24 [65] and MDA MB-231 [66] cells as were used in this manuscript.…”

Section: Effective Suppression Of Proliferation and Cell Viability Afsupporting

confidence: 66%

Curcumin Encapsulated in Crosslinked Cyclodextrin Nanoparticles Enables Immediate Inhibition of Cell Growth and Efficient Killing of Cancer Cells

2021

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The efficiency of anti-cancer drugs is commonly determined by endpoint assays after extended incubation times, often after days. Here we demonstrate that curcumin encapsulated in crosslinked cyclodextrin nanoparticles (CD-NP) acts extremely rapidly on cell metabolism resulting in an immediate and complete inhibition of cell growth and in efficient cancer-cell killing only few hours after incubation. This early onset of anti-cancer action was discovered by live-cell high-throughput fluorescence microscopy using an environmental stage. To date, only very few examples of covalently crosslinked nanoscale CD-based (CD-NP) drug carriers exist. Crosslinking cyclodextrins enables the adsorption of unusually high payloads of hydrophobic curcumin (762 µg CC/mg CD-NP) reflecting a molar ratio of 2.3:1 curcumin to cyclodextrin. We have investigated the effect of CD-NP encapsulated curcumin (CD-CC-NP) in comparison to free, DMSO-derived curcumin nanoparticles (CC-NP) on 4 different cell lines. Very short incubations times as low as 1 h were applied and cell responses after medium change were subsequently followed over two days. We show that cell proliferation is inhibited nearly immediately in all cell lines and that a cell- and concentration dependent cancer-cell killing occurs. Anti-cancer effects were similar with free and encapsulated curcumin, however, encapsulation in CD-NP drastically extends the long-term photostability and anti-cancer activity of curcumin. Curcumin-sensitivity is highest in HeLa cells reaching up to 90% cell death under these conditions. Sensitivity decreased from HeLa to T24 to MDA MB-231 cells. Strikingly, the immortalized non-cancerous cell line MCF-10A was robust against curcumin concentrations that were highly toxic to the other cell lines. Our results underline the potential of curcumin as gentle and yet effective natural anti-cancer agent when delivered solvent-free in stabilizing and biocompatible drug carriers such as CD-NP that enable efficient cellular delivery.

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Section: Effective Suppression Of Proliferation and Cell Viability Afsupporting

confidence: 66%

Curcumin Encapsulated in Crosslinked Cyclodextrin Nanoparticles Enables Immediate Inhibition of Cell Growth and Efficient Killing of Cancer Cells

2021

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“…Further, flavonoids such as chrysin have been shown exert positive effects on cancer cell inhibition at comparatively low concentrations, through synergistic effects influenced by one or more other phytochemicals and in low concentrations, compared to acting alone. Therefore, the study of the combinatorial effects of multiple flavonoids/flavonoids and phytochemicals in in vitro, pre-clinical and clinical conditions can be encouraged, which may have the ability to exert chemopreventive effects at lower concentrations [ 224 , 225 ]. Furthermore, due to the low oral bioavailability of luteolin, apigenin and chrysin, the special emphasis should be given to alternative modes of administration, such as intraperitoneal administration, concerning the potential use of these compounds in cancer treatment, but at safer doses [ 101 , 199 , 210 ].…”

Section: Discussionmentioning

confidence: 99%

Regulation of Nrf2/ARE Pathway by Dietary Flavonoids: A Friend or Foe for Cancer Management?

et al. 2020

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The nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cell signaling mechanism in maintaining redox homeostasis in humans. The role of dietary flavonoids in activating Nrf2/ARE in relation to cancer chemoprevention or cancer promotion is not well established. Here we summarize the dual effects of flavonoids in cancer chemoprevention and cancer promotion with respect to the regulation of the Nrf2/ARE pathway, while underlying the possible cellular mechanisms. Luteolin, apigenin, quercetin, myricetin, rutin, naringenin, epicatechin, and genistein activate the Nrf2/ARE pathway in both normal and cancer cells. The hormetic effect of flavonoids has been observed due to their antioxidant or prooxidant activity, depending on the concentrations. Reported in vitro and in vivo investigations suggest that the activation of the Nrf2/ARE pathway by either endogenous or exogenous stimuli under normal physiological conditions contributes to redox homeostasis, which may provide a mechanism for cancer chemoprevention. However, some flavonoids, such as luteolin, apigenin, myricetin, quercetin, naringenin, epicatechin, genistein, and daidzein, at low concentrations (1.5 to 20 µM) facilitate cancer cell growth and proliferation in vitro. Paradoxically, some flavonoids, including luteolin, apigenin, and chrysin, inhibit the Nrf2/ARE pathway in vitro. Therefore, even though flavonoids play a major role in cancer chemoprevention, due to their possible inducement of cancer cell growth, the effects of dietary flavonoids on cancer pathophysiology in patients or appropriate experimental animal models should be investigated systematically.

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“…Current challenges for cancer therapy with phytochemicals are, for example, the low solubility of compounds, cancer-specific delivery of compounds, and limited penetration of compounds into cancer. To overcome these impediments, the delivery of phytochemicals using nanoparticles has been investigated [ 38 , 337 ]. Moreover, the co-delivery of phytochemicals using nanoparticles displays synergistic effects on cancer cells ( Section 3.3.3 ), demonstrating an opportunity to develop a new combination strategy for cancer therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Besides, both chrysin and curcumin can stimulate the expression of miR-132 in breast cancer cells ( Figure 2 and Table 4 ). Additionally, the combinatorial treatment of chrysin with curcumin using nanoparticles boosts miR-132 expression and shows synergistic anti-cancer effects [ 38 ]. Through targeting forkhead box A1 (FOXA1), miR-132 shows an anti-proliferation effect on breast cancer cells [ 238 ].…”

Section: Tumor-suppressive Mirnas Induced By Phytochemicals Currenmentioning

confidence: 99%

Participation of MicroRNAs in the Treatment of Cancer with Phytochemicals

et al. 2020

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Cancer is a global health concern and one of the main causes of disease-related death. Even with considerable progress in investigations on cancer therapy, effective anti-cancer agents and regimens have thus far been insufficient. There has been compelling evidence that natural phytochemicals and their derivatives have potent anti-cancer activities. Plant-based anti-cancer agents, such as etoposide, irinotecan, paclitaxel, and vincristine, are currently being applied in medical treatments for patients with cancer. Further, the efficacy of plenty of phytochemicals has been evaluated to discover a promising candidate for cancer therapy. For developing more effective cancer therapy, it is required to apprehend the molecular mechanism deployed by natural compounds. MicroRNAs (miRNAs) have been realized to play a pivotal role in regulating cellular signaling pathways, affecting the efficacy of therapeutic agents in cancer. This review presents a feature of phytochemicals with anti-cancer activity, focusing mainly on the relationship between phytochemicals and miRNAs, with insights into the role of miRNAs as the mediators and the regulators of anti-cancer effects of phytochemicals.

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Synergistic Antiproliferative Effects of Co-nanoencapsulated Curcumin and Chrysin on MDA-MB-231 Breast Cancer Cells Through Upregulating miR-132 and miR-502c

Cited by 45 publications

References 56 publications

Curcumin Encapsulated in Crosslinked Cyclodextrin Nanoparticles Enables Immediate Inhibition of Cell Growth and Efficient Killing of Cancer Cells

Curcumin Encapsulated in Crosslinked Cyclodextrin Nanoparticles Enables Immediate Inhibition of Cell Growth and Efficient Killing of Cancer Cells

Regulation of Nrf2/ARE Pathway by Dietary Flavonoids: A Friend or Foe for Cancer Management?

Participation of MicroRNAs in the Treatment of Cancer with Phytochemicals

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