The synergistic impact of quinacrine on cell cycle and anti-invasiveness behaviors of doxorubicin in MDA-MB-231 breast cancer cells

Sabzichi, Mehdi; Ramezani, Mina; Mohammadian, Jamal; Ghorbani, Marjan; Mardomi, Alireza; Najafipour, Farzad; Mehdizadeh, Amir

doi:10.1016/j.procbio.2019.03.007

Cited by 24 publications

(16 citation statements)

References 33 publications

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“…The highest G 2 /M (1.6-fold) arrest was observed in PC. Conf with slight G 0 /G 1 (1.08-fold) and S (1.03-fold) arrest, which may be due to the inadequate Conf cell uptake as a result of its high hydrophobicity, insufficient concentration of Conf (sub IC 50 dose was used) and time-dependent function of Conf, which is consistent with results reported by Cheraghi et al 19 Dox caused an increase in the G 2 /M (1.33-fold) and sub-G 0 (6.62-fold) phases, but sub-G 0 was dominant, in agreement with that reported by Sabzichi et al 16 As could be understood from the above results, the nanoformulations (P2D, PD and PC) acted more efficiently than their related free drug forms (2D, Dox and Conf, respectively) in disturbing the cell cycle, consequently leading to cell apoptosis. 60,61 Fig.…”

Section: Cell Cycle Arrest Resultssupporting

confidence: 91%

“…5,6 A common way to decrease the side effects of Dox is the utilization of adjuvant compounds, which reduce the therapeutic dosage and keeps or increases the therapeutic outcome. 7 Different adjuvants are used in combination with Dox including cyclophosphamide, 8,9 5-uorouracil, 7,10 b-caryophyllene, 11 thiocyanoacetamide, 12 ifosfamide, 13 furanodiene, 14 quercetin, 15 quinacrine, 16 orange peel extract, naringin 17 and conferone. 18 Conferone is a natural and non-toxic compound, which is extracted from the fruits and roots of the self-growing Ferula species, which has signicant anticancer properties, such as antiangiogenic effects, suppressing P-glycoprotein (P-gp)mediated drug efflux, and increasing the cellular uptake and accumulation of Dox in cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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Novel pH-sensitive and biodegradable micelles for the combined delivery of doxorubicin and conferone to induce apoptosis in MDA-MB-231 breast cancer cell line

et al. 2020

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Section: Cell Cycle Arrest Resultssupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Novel pH-sensitive and biodegradable micelles for the combined delivery of doxorubicin and conferone to induce apoptosis in MDA-MB-231 breast cancer cell line

et al. 2020

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“…For this purpose, the cells were seeded on a 6-well plate (3×105 cells/well) and treated with docetaxel (2 nM), quinacrine (2.5 µM) or their combination for 24 hours. The cells were harvested from the plate and washed with phosphate buffer saline and then suspended in the binding buffer and stained with annexin V and propidium iodide (20). Flow cytometry analysis was performed using BD FACSCalibur ™ (BD Biosciences, Franklin Lakes, NJ, USA) and the FlowJo software (FlowJo LLC, Ashland, OR, USA).…”

Section: Methodsmentioning

confidence: 99%

Synergistic Effect of Docetaxel Combined with Quinacrine on Induction of Apoptosis and Reduction of Cell proliferation in a Lung Cancer Cell Line

Sofyani

Sharifi

2020

mljgoums

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Background and objectives: Combination chemotherapy with new adjuvants has been introduced as an innovative method of treating various types of cancer. The aim of this study was to investigate potential synergistic effect of quinacrine on the anti-proliferative and antiapoptotic activity of docetaxel in A549 lung cancer cells. Methods: Cell viability and apoptosis percentage were evaluated with MTT assay and annexin V staining. To understand the mechanisms through which quinacrine modulates expression of pro-apoptotic and anti-apoptotic genes, expression of Bcl-2, Bcl-xl and Bax genes were investigated using real-time RT-PCR. Results: The half maximal inhibitory concentration values for docetaxel and quinacrine was 3.16±1.5 nM and 4.4±0.58 μ M, respectively. The combination index value of docetaxel and quinacrine was 0.66 against A549 cells, indicating strong synergism. The expression of antiapoptotic genes Bcl-2 and Bcl-xl reduced significantly, while the expression of the pro-apoptotic gene Bax increased significantly after co-treatment with docetaxel and quinacrine (P<0.05). Treatment of cells with a combination of quinacrine and docetaxel significantly increased the inhibitory effect of docetaxel (reduced proliferation by 50%) and the percentage of apoptotic cells. Conclusion: Our findings suggest that the combination of quinacrine and docetaxel can be considered as a promising strategy for the treatment of patients with lung cancer.

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“…Adjuvants are the compounds that reduce the side-effects of anticancer drugs due to decrease of required therapeutic dose while keeping its desired therapeutic effects or even increasing it [1]. Various adjuvants were utilized for Doxorubicin (Dox) combination therapy, such as: orange peel and naringin extract [2], curcumin [3], quinacrine [4] and conferone [5,6]. Conferone (Conf) is an extraction of various parts (such as root and fruit) of Ferula class herbs.…”

Section: Introductionmentioning

confidence: 99%

Co-Delivery of Doxorubicin and Conferone by Novel pH-Responsive β-Cyclodextrin Grafted Micelles Triggers Apoptosis of Metastatic Human Breast Cancer Cells

Rahmani

Rahimi

Iranshahi

et al. 2021

Preprint

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Adjuvant-aided combination chemotherapy is one of the most effective ways of cancer treatment by overcoming the multidrug resistance (MDR) and reducing the side-effects of anticancer drugs. In this study Conferone (Conf) was used as adjuvant in combination with Doxorubicin (Dox) for induction of apoptosis to MDA-MB-231 cells. Herein, the novel biodegradable amphiphilic β-cyclodextrin grafted poly maleate-co-PLGA was synthesized by thiol-ene addition and ring-opening process. Micelles obtained from novel copolymer showed exceptional properties such as small size of around 34.5 nm, CMC of 0.1 μg/mL, and cell internalization of around 100 % at 30 min. These novel engineered micelles were used for combination delivery of doxorubicin-conferone with high encapsulation efficiency of near 100 % for both drugs. Our results show that combination delivery of Dox and Conf to MDA-MB-231 cells had synergistic effects (CI<1). According to cell cycle and Annexin-V apoptosis analysis, Dox-Conf loaded micelle significantly induce tumor cell apoptosis (more than 98 % of cells population showed apoptosis at IC50 = 0.259 μg/mL). RT-PCR and western-blot tests show that Dox-Conf loaded βCD-g-PMA-co-PLGA micelle induced apoptosis via intrinsic pathway. Therefore, the unique design of multi-functional pH-sensitive micelles open a new perspective for the development of nanomedicines for combination chemo-adjuvant therapy against malignant cancer.

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The synergistic impact of quinacrine on cell cycle and anti-invasiveness behaviors of doxorubicin in MDA-MB-231 breast cancer cells

Cited by 24 publications

References 33 publications

Novel pH-sensitive and biodegradable micelles for the combined delivery of doxorubicin and conferone to induce apoptosis in MDA-MB-231 breast cancer cell line

Novel pH-sensitive and biodegradable micelles for the combined delivery of doxorubicin and conferone to induce apoptosis in MDA-MB-231 breast cancer cell line

Synergistic Effect of Docetaxel Combined with Quinacrine on Induction of Apoptosis and Reduction of Cell proliferation in a Lung Cancer Cell Line

Co-Delivery of Doxorubicin and Conferone by Novel pH-Responsive β-Cyclodextrin Grafted Micelles Triggers Apoptosis of Metastatic Human Breast Cancer Cells

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