Plumbagin triggers DNA damage response, telomere dysfunction and genome instability of human breast cancer cells

Sameni, Safoura; Hande, M. Prakash

doi:10.1016/j.biopha.2016.05.007

Cited by 21 publications

(21 citation statements)

References 42 publications

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“…Several studies have reported the pharmacological properties of plumbagin, including anticancer activities on various types of cancer cell lines. The anticancer mechanisms of plumbagin are mostly associated with its anti-proliferative and apoptotic-inducing effects [ 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. However, the effect under the hypoxic conditions of plumbagin has not yet been investigated in breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Plumbagin Suppresses Breast Cancer Progression by Downregulating HIF-1α Expression via a PI3K/Akt/mTOR Independent Pathway under Hypoxic Condition

et al. 2022

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Hypoxia-inducible factor-1α (HIF-1α) is a major transcriptional regulator that plays a crucial role in the hypoxic response of rapidly growing tumors. Overexpression of HIF-1α has been associated with breast cancer metastasis and poor clinical prognosis. Plumbagin, the main phytochemical from Plumbago indica, exerts anticancer effects via multiple mechanisms. However, its precise mechanisms on breast cancer cells under hypoxic conditions has never been investigated. This study aims to examine the anticancer effect of plumbagin on MCF-7 cell viability, transcriptional activity, and protein expression of HIF-1α under normoxia and hypoxia-mimicking conditions, as well as reveal the underlying signaling pathways. The results demonstrate that plumbagin decreased MCF-7 cell viability under normoxic conditions, and a greater extent of reduction was observed upon exposure to hypoxic conditions induced by cobalt chloride (CoCl2). Mechanistically, MCF-7 cells upregulated the expression of HIF-1α protein, mRNA, and the VEGF target gene under CoCl2-induced hypoxia, which were abolished by plumbagin treatment. In addition, inhibition of HIF-1α and its downstream targets did not affect the signaling transduction of the PI3K/Akt/mTOR pathway under hypoxic state. This study provides mechanistic insight into the anticancer activity of plumbagin in breast cancer cells under hypoxic conditions by abolishing HIF-1α at transcription and post-translational modifications.

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Section: Introductionmentioning

confidence: 99%

Plumbagin Suppresses Breast Cancer Progression by Downregulating HIF-1α Expression via a PI3K/Akt/mTOR Independent Pathway under Hypoxic Condition

et al. 2022

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“…A similar observation was made in the study by Giovanna et al (2020), using Hep-G2/C3A cells, where PLB was shown to trigger double-strand DNA damage (DSBs) [ 22 ]. In human breast cancer cells, plumbagin was also shown to induce DSBs in all the studied cell types, which may initiate compensatory and self-destructive mechanisms [ 40 ]. In this study, cells containing phosphorylated H2AX (γ-H2AX) foci clearly increased at high PLB concentrations.…”

Section: Discussionmentioning

confidence: 99%

Plumbagin Exhibits Genotoxicity and Induces G2/M Cell Cycle Arrest via ROS-Mediated Oxidative Stress and Activation of ATM-p53 Signaling Pathway in Hepatocellular Cells

Liu

Zhang

Jin

et al. 2023

IJMS

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Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone, PLB), a naturally occurring naphthoquinone mainly isolated from the plant Plumbago zeylanica L., has been proven to possess anticancer activities towards multiple types of cancer. Although there has been an increasing amount of research regarding its anticancer effects, the association between oxidative stress, genotoxicity and the cell cycle arrest induced by PLB still remains unclear. Therefore, it is important to investigate their potential connections and the involvement of DNA damage and the ataxia telangiectasia mutated protein (ATM)-p53 signaling pathway in PLB’s anticancer mechanism. The present study showed that PLB exposure significantly reduced HCC cell viability and colony formation. In addition, PLB-induced G2/M cell cycle arrest, oxidative stress, and DNA damage was detected, which could be almost blocked by NAC pretreatment. PLB could trigger a DNA damage response by activating cell cycle checkpoints such as ATM, checkpoint kinase 1 (Chk1), checkpoint kinase 2 (Chk2) and p53. Meanwhile, the key modulator of the G2/M transition factor, Cell Division Cycle 25C (cdc25C), was significantly downregulated in an ROS-dependent manner. Furthermore, pretreatment with ATM and p53 inhibitors (KU55933 and Pifithrin-α) could reduce the occurrence of G2/M cell cycle arrest by inhibiting the activation of the ATM-p53 pathway. Taken together, these results indicate that ROS-mediated oxidative stress plays a key role in PLB-induced G2/M cell cycle arrest mediated by the ATM-p53 pathway.

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“…Chrysin [25] Plumbagin [26] DNA damage and condensation DNA double-strand break repair DNA damage Sustained proliferative signaling Resveratrol [27] Perillyl alcohol [28] Artemisinin [29] Cell cycle…”

Section: Genomic Instability Allyl Isothiocyanatementioning

confidence: 99%

Tackling heterogeneity in treatment-resistant breast cancer using a broad-spectrum therapeutic approach

Lowe¹,

LaValley²,

Felsher³

2022

Cancer Drug Resist

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Tumor heterogeneity can contribute to the development of therapeutic resistance in cancer, including advanced breast cancers. The object of the Halifax project was to identify new treatments that would address mechanisms of therapeutic resistance through tumor heterogeneity by uncovering combinations of therapeutics that could target the hallmarks of cancer rather than focusing on individual gene products. A taskforce of 180 cancer researchers, used molecular profiling to highlight key targets responsible for each of the hallmarks of cancer and then find existing therapeutic agents that could be used to reach those targets with limited toxicity. In many cases, natural health products and re-purposed pharmaceuticals were identified as potential agents. Hence, by combining the molecular profiling of tumors with therapeutics that target the hallmark features of cancer, the heterogeneity of advanced-stage breast cancers can be addressed.

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Plumbagin triggers DNA damage response, telomere dysfunction and genome instability of human breast cancer cells

Cited by 21 publications

References 42 publications

Plumbagin Suppresses Breast Cancer Progression by Downregulating HIF-1α Expression via a PI3K/Akt/mTOR Independent Pathway under Hypoxic Condition

Plumbagin Suppresses Breast Cancer Progression by Downregulating HIF-1α Expression via a PI3K/Akt/mTOR Independent Pathway under Hypoxic Condition

Plumbagin Exhibits Genotoxicity and Induces G2/M Cell Cycle Arrest via ROS-Mediated Oxidative Stress and Activation of ATM-p53 Signaling Pathway in Hepatocellular Cells

Tackling heterogeneity in treatment-resistant breast cancer using a broad-spectrum therapeutic approach

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