Genistein potentiates Centchroman induced antineoplasticity in breast cancer via PI3K/Akt deactivation and ROS dependent induction of apoptosis

Kaushik, Shweta; Shyam, Hari; Agarwal, S. C.; Sharma, Rishi; Nag, Tapas Chandra; Dwivedi, Anil Kumar; Balapure, Anil K.

doi:10.1016/j.lfs.2019.117073

Cited by 45 publications

(20 citation statements)

References 32 publications

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“…Isoflavone genistein promoted breast cancer cell arrest at G2/M phase and subsequent ROS dependent apoptosis [59]. Daidzein promoted apoptosis in breast cancer MCF-7 cells due to the ROS generation [60].…”

Section: Flavonoids In Oxidative Stressmentioning

confidence: 99%

Flavonoids as Anticancer Agents

et al. 2020

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Flavonoids are polyphenolic compounds subdivided into 6 groups: isoflavonoids, flavanones, flavanols, flavonols, flavones and anthocyanidins found in a variety of plants. Fruits, vegetables, plant-derived beverages such as green tea, wine and cocoa-based products are the main dietary sources of flavonoids. Flavonoids have been shown to possess a wide variety of anticancer effects: they modulate reactive oxygen species (ROS)-scavenging enzyme activities, participate in arresting the cell cycle, induce apoptosis, autophagy, and suppress cancer cell proliferation and invasiveness. Flavonoids have dual action regarding ROS homeostasis—they act as antioxidants under normal conditions and are potent pro-oxidants in cancer cells triggering the apoptotic pathways and downregulating pro-inflammatory signaling pathways. This article reviews the biochemical properties and bioavailability of flavonoids, their anticancer activity and its mechanisms of action.

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Section: Flavonoids In Oxidative Stressmentioning

confidence: 99%

Flavonoids as Anticancer Agents

et al. 2020

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“…Reactive oxygen species (ROS) are important signalling molecules in cells, which participate in the transmission of information via multiple signalling pathways [2,3]. Excessive ROS induce tumour cell autophagy and apoptosis by inhibiting PI3K/Akt and other pathways, thereby inhibiting the occurrence and development of tumours [4].…”

Section: Introductionmentioning

confidence: 99%

BDH2 triggers ROS-induced cell death and autophagy by promoting Nrf2 ubiquitination in gastric cancer

Liu

Feng

et al. 2020

J Exp Clin Cancer Res

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Background: 3-Hydroxy butyrate dehydrogenase 2 (BDH2) is a short-chain dehydrogenase/reductase family member that plays a key role in the development and pathogenesis of human cancers. However, the role of BDH2 in gastric cancer (GC) remains largely unclear. Our study aimed to ascertain the regulatory mechanisms of BDH2 in GC, which could be used to develop new therapeutic strategies. Methods: Western blotting, immunohistochemistry, and RT-PCR were used to investigate the expression of BDH2 in GC specimens and cell lines. Its correlation with the clinicopathological characteristics and prognosis of GC patients was analysed. Functional assays, such as CCK-8 and TUNEL assays, transmission electron microscopy, and an in vivo tumour growth assay, were performed to examine the proliferation, apoptosis, and autophagy of GC cells. Related molecular mechanisms were clarified by luciferase reporter, coimmunoprecipitation, and ubiquitination assays. Results: BDH2 was markedly downregulated in GC tissues and cells, and the low expression of BDH2 was associated with poor survival of GC patients. Functionally, BDH2 overexpression significantly induced apoptosis and autophagy in vitro and in vivo. Mechanistically, BDH2 promoted Keap1 interaction with Nrf2 to increase the ubiquitination level of Nrf2. Ubiquitination/degradation of Nrf2 inhibited the activity of ARE to increase accumulation of reactive oxygen species (ROS), thereby inhibiting the phosphorylation levels of Akt Ser473 and mTOR Ser2448. Conclusions: Our study indicates that BDH2 is an important tumour suppressor in GC. BDH2 regulates intracellular ROS levels to mediate the PI3K/Akt/mTOR pathway through Keap1/Nrf2/ARE signalling, thereby inhibiting the growth of GC.

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“…It causes proteolytic cleavage dependent activation of PARP as well as activator and executioner caspases of the intrinsic pathway. It also causes aberration in Bcl2/Bax, leading to the disruption of the mitochondrial membrane and production of ROS [ 38 , 40 , 41 ]. An in vitro study demonstrated that long-term exposure to genistein significantly reduced cellular levels of the EGF receptor, which is upstream of the Akt and JAK/STAT pathway [ 40 ].…”

Section: Introductionmentioning

confidence: 99%

Genistein as a regulator of signaling pathways and microRNAs in different types of cancers

et al. 2021

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Cancers are complex diseases orchestrated by a plethora of extrinsic and intrinsic factors. Research spanning over several decades has provided better understanding of complex molecular interactions responsible for the multifaceted nature of cancer. Recent advances in the field of next generation sequencing and functional genomics have brought us closer towards unravelling the complexities of tumor microenvironment (tumor heterogeneity) and deregulated signaling cascades responsible for proliferation and survival of tumor cells. Phytochemicals have begun to emerge as potent beneficial substances aimed to target deregulated signaling pathways. Isoflavonoid genistein is an essential phytochemical involved in regulation of key biological processes including those in different types of cancer. Emerging preclinical evidence have shown its anti-cancer, anti-inflammatory and anti-oxidant properties. Testing of this substance is in various phases of clinical trials. Comprehensive preclinical and clinical trials data is providing insight on genistein as a modulator of various signaling pathways both at transcription and translation levels. In this review we have explained the mechanistic regulation of several key cellular pathways by genistein. We have also addressed in detail various microRNAs regulated by genistein in different types of cancer. Moreover, application of nano-formulations to increase the efficiency of genistein is also discussed. Understanding the pleiotropic potential of genistein to regulate key cellular pathways and development of efficient drug delivery system will bring us a step towards designing better chemotherapeutics.

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Genistein potentiates Centchroman induced antineoplasticity in breast cancer via PI3K/Akt deactivation and ROS dependent induction of apoptosis

Cited by 45 publications

References 32 publications

Flavonoids as Anticancer Agents

Flavonoids as Anticancer Agents

BDH2 triggers ROS-induced cell death and autophagy by promoting Nrf2 ubiquitination in gastric cancer

Genistein as a regulator of signaling pathways and microRNAs in different types of cancers

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