Anticancer potential of myricetin bulk and nano forms in vitro in lymphocytes from myeloma patients
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GENOTOXICITY AND CARCINOGENICITY
Anticancer potential of myricetin bulk and nano forms in vitro in lymphocytes from myeloma patients Shabana Akhtar1 · Mojgan Najafzadeh1 · Mohammad Isreb2 · Lisa Newton3 · Rajendran C. Gopalan2 · Diana Anderson1 Received: 20 August 2020 / Accepted: 20 October 2020 © The Author(s) 2020
Abstract Evading apoptosis and chemo-resistance are considered as very important factors which help tumour progression and metastasis. Hence, to overcome chemo-resistance, there is an urgent requirement for emergence of more effective treatment options. Myricetin, a naturally occurring flavonoid, is present in various plant-derived foods and shows antitumour potential in different cancers. In the present in vitro study, results from the comet assay demonstrated that myricetin bulk (10 µM) and nano (20 µM) forms exhibited a non-significant level of genotoxicity in lymphocytes from multiple myeloma patients when compared to those from healthy individuals. Western blot results showed a decrease in Bcl-2/Bax ratio and an increase in P53 protein levels in lymphocytes from myeloma patients, but not in lymphocytes from healthy individuals. A significant increase in intracellular reactive oxygen species level was also observed, suggesting that regulation of apoptotic proteins triggered by myricetin exposure in lymphocytes from myeloma patients occurred through P53 and oxidative stress-dependent pathways. The potency of myricetin against lymphocytes from myeloma patients marks it a potential candidate to be considered as an alternative to overcome chemo-resistance in cancer therapies. Keywords Myricetin · Lymphocytes · Myeloma · Intrinsic-apoptotic proteins · Oxidative stress · P53
Introduction Cancer is a serious threat to human health and life at present that is constantly increasing (Yang et al. 2011). Chemotherapy, steroids, biological therapies and possibly stem cell transplant are the treatment methods currently being utilised for the therapy of multiple myeloma (MM) cancer. Initially, chemotherapy combined with other treatment works effectively, but myeloma patients usually always have a relapse and these drugs also cause various side effects including alopecia, nausea, neuropathy, etc.; therefore, more careful drugs and novel therapies are required for human cancers (Huang et al. 2015).
* Diana Anderson [email protected] 1
School of Chemistry and Biosciences, University of Bradford, Bradford, UK
2
School of Pharmacy and Medical Sciences, University of Bradford, Bradford, UK
3
Bradford Royal Infirmary (BRI), Bradford, UK
Cell cycle ensures the homeostasis in an organ, while a dysregulation in any of its steps or components could lead to cancer development. The molecular targets involved in the cell cycle regulatory mechanisms are the main focus of investigational anticancer drugs (Diaz-Moralli et al. 2013). The maintenance of apoptosis balance is highly essential for normal cellular growth, as excessive apoptosis causes atrophy, whereas faulty apoptosis leads to uncontrolled
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