Quinacrine and curcumin synergistically increased the breast cancer stem cells death by inhibiting ABCG2 and modulating DNA damage repair pathway

Nayak, Deepika; Tripathi, Neha; Kathuria, Deepika; Siddharth, Sumit; Nayak, Anmada; Bharatam, Prasad V.; Kundu, Chanakya Nath

doi:10.1016/j.biocel.2019.105682

Cited by 35 publications

(31 citation statements)

References 50 publications

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“…The first discovered pharmacological activity of curcumin is an antibacterial effect, found in 1949 [29]. Further studies focused on revealing other therapeutic and biological activities of curcumin including antiproliferative [30], antimetastatic [31], antioxidant [32], anti-inflammatory [33], antidiabetic [34], antiangiogenic [35], immunomodulatory [36], antitumor [37], antiatherosclerotic [38] and a lipid lowering effect [39] and regulating blood pressure [40].…”

Section: Curcumin: Structure and Pharmacokineticsmentioning

confidence: 99%

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

et al. 2020

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Doxorubicin (DOX) is a well-known chemotherapeutic agent extensively applied in the field of cancer therapy. However, similar to other chemotherapeutic agents such as cisplatin, paclitaxel, docetaxel, etoposide and oxaliplatin, cancer cells are able to obtain chemoresistance that limits DOX efficacy. In respect to dose-dependent side effect of DOX, enhancing its dosage is not recommended for effective cancer chemotherapy. Therefore, different strategies have been considered for reversing DOX resistance and diminishing its side effects. Phytochemical are potential candidates in this case due to their great pharmacological activities. Curcumin is a potential antitumor phytochemical isolated from Curcuma longa with capacity of suppressing cancer metastasis and proliferation and affecting molecular pathways. Experiments have demonstrated the potential of curcumin for inhibiting chemoresistance by downregulating oncogene pathways such as MMP-2, TGF-β, EMT, PI3K/Akt, NF-κB and AP-1. Furthermore, coadministration of curcumin and DOX potentiates apoptosis induction in cancer cells. In light of this, nanoplatforms have been employed for codelivery of curcumin and DOX. This results in promoting the bioavailability and internalization of the aforementioned active compounds in cancer cells and, consequently, enhancing their antitumor activity. Noteworthy, curcumin has been applied for reducing adverse effects of DOX on normal cells and tissues via reducing inflammation, oxidative stress and apoptosis. The current review highlights the anticancer mechanism, side effects and codelivery of curcumin and DOX via nanovehicles.

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Section: Curcumin: Structure and Pharmacokineticsmentioning

confidence: 99%

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

et al. 2020

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“…As a complementary medicine to carboplatin, curcumin reduces its adverse effects by selectively activating nucleotide excision repair and homologous recombination in bone marrow cells through positive regulation of BRCA1, BRCA2, and ERCC1 expression, but it has the opposite effect on malignant cells (50). Together with quinacrine, curcumin binds DNA more efficiently, being able to cause further damage to breast cancer stem cells and preventing their repair by lowering the expression of DDB2, Polb, Pold, PolH, Rad51, Fen1, XRCC1, CHK1, and RPA proteins (51). Curcumin increases the apoptotic effects of cisplatin on cisplatinresistant lung adenocarcinoma cells by inhibiting FANCD2 monoubiquitination and, therefore, also preventing activation of the Fanconi anemia/BRCA pathway that enables DNA repair by homologous recombination (52).…”

Section: Curcuminmentioning

confidence: 99%

Natural Compounds That Target DNA Repair Pathways and Their Therapeutic Potential to Counteract Cancer Cells

Lagunas‐Rangel

Bermúdez‐Cruz

2020

Front. Oncol.

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Resistance to current cancer treatments is an important problem that arises through various mechanisms, but one that stands out involves an overexpression of several factors associated with DNA repair. To counteract this type of resistance, different drugs have been developed to affect one or more DNA repair pathways, therefore, to test different compounds of natural origin that have been shown to induce cell death in cancer cells is paramount. Since natural compounds target components of the DNA repair pathways, they have been shown to promote cancer cells to be resensitized to current treatments. For this and other reasons, natural compounds have aroused great curiosity and several research projects are being developed around the world to establish combined treatments between them and radio or chemotherapy. In this work, we summarize the effects of different natural compounds on the DNA repair mechanisms of cancer cells and emphasize their possible application to re-sensitize these cells.

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“…For example, Nayak et al [65] showed the ability of quinacrine and curcumin to regulate the apoptosis of cancer stem cells with an in vitro model. Curcumin is a diarylheptanoid, which is a natural phenol isolated from the Curcuma longa plant, and has multiple pleiotropic effects, such as the suppression of multiple signaling pathways, the inhibition of cell proliferation, and antimetastatic properties [66].…”

Section: Combination Of Drugsmentioning

confidence: 99%

“…Its antiapoptotic activity is shown by its ability to arrest the cell cycle in the S-phase via the inactivation of topoisomerase activity, the activation of p53 and p21, and the inhibition of NF-kβ [67]. The study of Nayak et al [65] analyzed the anticancer effects of curcumin and quinacrine, as well as their combination, using in vitro and molecular modeling. Multiple BC cells were used to characterize a metastatic model that demonstrated the effects of the combination of molecules on decreasing the migration and invasion and inducing apoptosis.…”

Section: Combination Of Drugsmentioning

confidence: 99%

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Integration of Molecular Docking and In Vitro Studies: A Powerful Approach for Drug Discovery in Breast Cancer

Cava

Castiglioni

2020

Applied Sciences

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Molecular docking in the pharmaceutical industry is a powerful in silico approach for discovering novel therapies for unmet medical needs predicting drug–target interactions. It not only provides binding affinity between drugs and targets at the atomic level, but also elucidates the fundamental pharmacological properties of specific drugs. The purpose of this review was to illustrate newer and emergent uses of docking when combined with in vitro techniques for drug discovery in metastatic breast cancer. We grouped the selected articles into five main categories; namely, systematic repositioning of drugs, natural drugs, new synthesized molecules, combinations of drugs, and drug latentiation. We focused on new promising drugs that have a good affinity with their targets, thus inducing a favorable biological response. This review suggests that the integration of molecular docking and in vitro studies can accelerate cancer drug discovery showing a good consistency of the results between the two approaches.

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Quinacrine and curcumin synergistically increased the breast cancer stem cells death by inhibiting ABCG2 and modulating DNA damage repair pathway

Cited by 35 publications

References 50 publications

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

Natural Compounds That Target DNA Repair Pathways and Their Therapeutic Potential to Counteract Cancer Cells

Integration of Molecular Docking and In Vitro Studies: A Powerful Approach for Drug Discovery in Breast Cancer

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