Polyphenols act synergistically with doxorubicin and etoposide in leukaemia cell lines

Mahbub, AA; Maitre, Christine L. Le; Haywood-Small, SL; Cross, Neil; Jordan-Mahy, Nicola

doi:10.1038/cddiscovery.2015.43

Cited by 54 publications

(86 citation statements)

References 23 publications

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“…Similar effects were seen with its isomer, emodin (1,3,8-trihydroxy-6-methylanthraquinone) (23). Both compounds produced a synergistic effect when combined with etoposide and doxorubicin on both lymphoid cell lines (24). The combination of aloe emodin and radiation enhanced radiosensitivity and apoptosis of cervical cancer cells, HeLa, compared to treatment with aloe emodin or radiation alone (25).…”

Section: Discussionsupporting

confidence: 54%

ALOE EMODIN ENHANCES TAMOXIFEN CYTOTOXICITY EFFECT ON ERa-POSITIVE BREAST CANCER CELLS, MCF-7, THROUGH DOWNREGULATION OF MEK1 AND MEK2

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et al. 2016

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The positive response to tamoxifen in ERa-positive breast cancer patients is usually of a short duration as many of the patients eventually develop resistance. Our preliminary results show that aloe emodin extracted from the leaves of the Aloe barbadensis Miller demonstrated a cytotoxicity that is selective to ERa-positive breast cancer cells (MCF-7), but not to ERa-negative breast cancer cells (MDA-MB-231) and to the control cells (MCF-10A). The objective of this study was to test the hypothesis that aloe emodin may enhance the response of MCF-7 cells to treatment with tamoxifen. MCF-7 cells were treated with aloe emodin alone, tamoxifen alone or a combination of emodin and tamoxifen, at their respective IC 50 concentrations and at different time points of 24 hours, 48 hours and 72 hours. The respective IC 50s were the concentrations of aloe emodin and tamoxifen required to achieve 50% inhibition of the cells in the study. Cell viability and apoptosis were determined using trypan blue exclusion and DNA fragmentation assays, respectively. The involvement of RAS/MEKs/ERKs genes of MAPK signalling pathways with aloe emodin was determined using QuantiGene 2.0 Plex assay. Data was evaluated using the one-way ANOVA test. Our findings showed that aloe emodin enhanced the cytotoxicity of tamoxifen on MCF-7 cells through apoptosis by downregulation of MEK1/2 genes. Our research may provide a rational basis for further in vivo studies to verify the efficacy of a combination of aloe emodin and tamoxifen on the viability of ERa-positive-breast cancer cells.

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Section: Discussionsupporting

confidence: 54%

ALOE EMODIN ENHANCES TAMOXIFEN CYTOTOXICITY EFFECT ON ERa-POSITIVE BREAST CANCER CELLS, MCF-7, THROUGH DOWNREGULATION OF MEK1 AND MEK2

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et al. 2016

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“…To enhance their antitumor effects and to minimize their limitation, co-administration with other targeted drugs has been widely tested and has achieved great success in clinical applications. Studies have shown that co-administration with apigenin significantly enhances the anti-cancer efficacy of chemodrugs and helps overcome their limitations in various types of cancers by targeting multiple signaling pathways (Table 2 ) [ 44 , 114 – 122 ].…”

Section: Combination Therapy For Apigeninmentioning

confidence: 99%

Apigenin in cancer therapy: anti-cancer effects and mechanisms of action

et al. 2017

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Apigenin is a common dietary flavonoid that is abundantly present in many fruits, vegetables and Chinese medicinal herbs and serves multiple physiological functions, such as strong anti-inflammatory, antioxidant, antibacterial and antiviral activities and blood pressure reduction. Therefore, apigenin has been used as a traditional medicine for centuries. Recently, apigenin has been widely investigated for its anti-cancer activities and low toxicity. Apigenin was reported to suppress various human cancers in vitro and in vivo by multiple biological effects, such as triggering cell apoptosis and autophagy, inducing cell cycle arrest, suppressing cell migration and invasion, and stimulating an immune response. In this review, we focus on the most recent advances in the anti-cancer effects of apigenin and their underlying mechanisms, and we summarize the signaling pathways modulated by apigenin, including the PI3K/AKT, MAPK/ERK, JAK/STAT, NF-κB and Wnt/β-catenin pathways. We also discuss combinatorial strategies to enhance the anti-cancer effect of apigenin on various cancers and its use as an adjuvant chemotherapeutic agent to overcome cancer drug resistance or to alleviate other adverse effects of chemotherapy. The functions of apigenin against cancer stem cells are also summarized and discussed. These data demonstrate that apigenin is a promising reagent for cancer therapy. Apigenin appears to have the potential to be developed either as a dietary supplement or as an adjuvant chemotherapeutic agent for cancer therapy.

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“…However, anti-tumor actions of flavonoids aid in the increase in the effectiveness of chemotherapy [ 8 ]. There have been several reports of sensitization of cancer cells to doxorubicin by apigenin and hesperidin [ 23 , 36 , 37 , 38 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…The second mechanism of action is related to the generation of oxidative stress, both in cancer and healthy cells [ 34 , 35 ]. Synergistic effects of doxorubicin and certain flavonoids, including apigenin and hesperidin, have been repeatedly demonstrated in different types of cancer cells [ 23 , 36 , 37 , 38 , 39 ]. However, the exact mechanism of this phenomenon has not been explained.…”

Section: Introductionmentioning

confidence: 99%

Apigenin and Hesperidin Downregulate DNA Repair Genes in MCF-7 Breast Cancer Cells and Augment Doxorubicin Toxicity

et al. 2020

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A number of studies have confirmed anti-tumor activity of flavonoids and their ability to enhance the effectiveness of classical anticancer drugs. The mechanism of this phenomenon is difficult to explain because of the ambivalent nature of these compounds. Many therapeutic properties of these compounds are attributed to their antioxidant activity; however, it is known that they can act as oxidants. The aim of this study was to assess the influence of apigenin and hesperidin on MCF-7 breast cancer cells with doxorubicin. The cytotoxic effect was determined using an MTT test and cell cycle analysis. To evaluate the possible interaction mechanism, reduced glutathione levels, as well as the DNA oxidative damage and the double strand breaks, were evaluated. Additionally, mRNA expression of genes related to DNA repair was assessed. It was demonstrated that flavonoids intensified the cytotoxic effect of doxorubicin despite flavonoids reduced oxidative damage caused by the drug. At the same time, the number of double strand breaks significantly increased and expression of tested genes was downregulated. In conclusion, both apigenin and hesperidin enhance the cytotoxic effects of doxorubicin on breast cancer cells, and this phenomenon occurs regardless of oxidative stress but is accompanied by disorders of DNA damage response mechanisms.

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Polyphenols act synergistically with doxorubicin and etoposide in leukaemia cell lines

Cited by 54 publications

References 23 publications

ALOE EMODIN ENHANCES TAMOXIFEN CYTOTOXICITY EFFECT ON ERa-POSITIVE BREAST CANCER CELLS, MCF-7, THROUGH DOWNREGULATION OF MEK1 AND MEK2

ALOE EMODIN ENHANCES TAMOXIFEN CYTOTOXICITY EFFECT ON ERa-POSITIVE BREAST CANCER CELLS, MCF-7, THROUGH DOWNREGULATION OF MEK1 AND MEK2

Apigenin in cancer therapy: anti-cancer effects and mechanisms of action

Apigenin and Hesperidin Downregulate DNA Repair Genes in MCF-7 Breast Cancer Cells and Augment Doxorubicin Toxicity

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