Targeting oncogenic transcription factors by polyphenols: A novel approach for cancer therapy

Rajagopal, Chitra; Lankadasari, Manendra Babu; Aranjani, Jesil Mathew; Harikumar, Kuzhuvelil B.

doi:10.1016/j.phrs.2017.12.034

Cited by 99 publications

(73 citation statements)

References 278 publications

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“…Many phytochemicals have been found to suppress the growth of cancer cells without affecting normal cells, to exhibit chemoprophylaxis effects, and to promote the sensitivity of cancer cells to DOX . Resveratrol (RES), known as a type of polyphenol compounds extracted from peanut, grape (red wine), tiger cane, mulberry, and other plants, has attracted increasing attention because of its varied healthy benefits . RES is of key importance in aging, neurological dysfunction, angiocardiopathy, and inflammation diseases.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol promotes sensitization to Doxorubicin by inhibiting epithelial‐mesenchymal transition and modulating SIRT1/β‐catenin signaling pathway in breast cancer

et al. 2019

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Breast cancer is one of the leading fatal diseases for women worldwide who cannot have surgery typically have to rely on systemic chemotherapy to extend their survival. Doxorubicin (DOX) is one of the most commonly used chemotherapeutic agents against breast cancer, but acquired resistance to DOX can seriously impede the efficacy of chemotherapy, leading to poor prognosis and recurrences of cancer. Resveratrol (RES) is a phytoalexin with pharmacological antitumor properties, but its underlying mechanisms are not clearly understood in the treatment of DOX‐resistant breast cancer. We used cell viability assays, cell scratch tests, and transwell assays combined with Western blotting and immunofluorescent staining to evaluate the effects of RES on chemoresistance and the epithelial‐mesenchymal transitions (EMTs) in adriamycin‐resistant MCF7/ADR breast cancer cells, and to investigate its underlying mechanisms. The results showed that a treatment of RES combining with DOX effectively inhibited cell growth, suppressed cell migration, and promoted cell apoptosis. RES reversed EMT properties of MCF7/ADR cells by modulating the connection between SIRT1 and β‐catenin, which provides a hopeful therapeutic avenue to conquer DOX‐resistance and thereby prolong survival rates in breast cancer patients.

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Section: Introductionmentioning

confidence: 99%

Resveratrol promotes sensitization to Doxorubicin by inhibiting epithelial‐mesenchymal transition and modulating SIRT1/β‐catenin signaling pathway in breast cancer

et al. 2019

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“…It is possible that some of the cardioprotective effects of this agent occur in part through promotion of cellular stress resistance in cardiomyocytes, although importantly we have not directly assessed the effects of carvedilol on this cell type. Likewise, cardamonin is a spice-derived nutraceutical with anti-neoplastic and 21 anti-inflammatory properties, which may involve modulation of the activity of STAT3 and other transcription factors 62 .…”

Section: Discussionmentioning

confidence: 99%

High throughput small molecule screening reveals NRF2-dependent and - independent pathways of cellular stress resistance

Lombard

Köhler

Guo

et al. 2019

Preprint

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Biological aging is the dominant risk factor for most chronic diseases. Development of anti-aging interventions offers the promise of preventing many such illnesses simultaneously. Cellular stress resistance is an evolutionarily conserved feature of longevity. Here, we identify compounds that induced resistance to the superoxide generator paraquat (PQ), the heavy metal cadmium (Cd), and the DNA alkylator methyl methanesulfonate (MMS). Some rescue compounds conferred resistance to a single stressor, while others provoked multiplex resistance. Induction of stress resistance in fibroblasts was predictive of longevity extension in a published large-scale longevity screen in C. elegans. Transcriptomic analysis implicated Nrf2 signaling in stress resistance provided by two protective compounds, cardamonin and AEG 3482.Molecules that conferred stress resistance also induced cellular inflammatory pathways, and other core pathways such as AMPK signaling. Small molecules identified in this work may represent attractive candidates to evaluate for their potential pro-health and pro-longevity effects in mammals.

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“…The anticancer properties of natural products have been suggested to play an important role in the prevention of cancers (Li et al, ). Gossypin is traditionally used for the treatment of diabetes (Venkatesan & Sorimuthu Pillai, ) and exerts anti‐inflammatory (Rajagopal, Lankadasari, Aranjani, & Harikumar, ), antioxidant (Katary & Salahuddin, ), and anticancer activities (Babu et al, ). However, the mechanistic targets of gossypin have not been clearly elucidated.…”

Section: Discussionmentioning

confidence: 99%

Gossypin inhibits gastric cancer growth by direct targeting of AURKA and RSK2

Wang

Chen

et al. 2018

Phytotherapy Research

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Gossypin is a flavone extracted from Hibiscus vitifolius, which has been reported to exhibit anti‐inflammatory, antioxidant, and anticancer activities. However, the anticancer properties of gossypin and its molecular mechanism of action against gastric cancer have not been fully investigated. In the present study, we report that gossypin is an Aurora kinase A (AURKA) and RSK2 inhibitor that suppresses gastric cancer growth. Gossypin attenuated anchorage‐dependent and anchorage‐independent gastric cancer cell growth as well as cell migration. Based on the results of in vitro screening and cell‐based assays, gossypin directly binds to and inhibits AURKA and RSK2 activities and their downstream signaling proteins. Gossypin decreased S phase and increased G2/M phase cell cycle arrest by reducing the expression of cyclin A2 and cyclin B1 and the phosphorylation of the CDC protein. Additionally, gossypin also induced intrinsic apoptosis by activating caspases and PARP and increasing the expression of cytochrome c. Our results demonstrate that gossypin is an AURKA and RSK2 inhibitor that could be useful for treating gastric cancer.

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Targeting oncogenic transcription factors by polyphenols: A novel approach for cancer therapy

Cited by 99 publications

References 278 publications

Resveratrol promotes sensitization to Doxorubicin by inhibiting epithelial‐mesenchymal transition and modulating SIRT1/β‐catenin signaling pathway in breast cancer

Resveratrol promotes sensitization to Doxorubicin by inhibiting epithelial‐mesenchymal transition and modulating SIRT1/β‐catenin signaling pathway in breast cancer

High throughput small molecule screening reveals NRF2-dependent and - independent pathways of cellular stress resistance

Gossypin inhibits gastric cancer growth by direct targeting of AURKA and RSK2

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