Figure 1 - uploaded by Franklyn S. De Silva
Content may be subject to copyright.
Combination effect of Metformin with secoisolariciresinol (SECO) and enterolactone (ENL) in SKBR3 cells. Cells were treated with metformin (0.3-20 mM) (open circle, solid line) and with 25 mM (closed circle, dashed line) or 50 mM (open triangle, dashed line) of A: SECO or B: ENL for 72 h. Cell viability was determined using Calcein AM cell viability assay conducted in triplicate on three separate occasions. Panel A, 50 mM SECO combined with 2.5, 5.0, or 10 mM metformin significantly reduced cell viability (P < 0.0001). Panel B, only 50 mM ENL combined with 0.3 mM metformin demonstrated significant reductions in cell viability (P < 0.05). Enterolactone-glucuronide did not alter cell viability in combination with metformin (data not shown).
Source publication
Systemic cytotoxic chemotherapy remains the mainstay of metastatic breast cancer; however, prognosis and overall survival is unfavorable due to inadequate treatment response and/or unacceptable toxicity. Natural compounds and their active metabolites receive increasing attention as possible adjuvant therapy with cancer chemotherapeutics to improve...
Contexts in source publication
Context 1
... investigate whether flaxseed lignans may enhance cytotoxicity of anticancer agents in HER2 positive breast cancer, cytotoxicity assays with four different anticancer drugs were conducted in SKBR3 cells in the absence and presence of SECO, ENL, and ENL-Gluc (Table 2 and Fig. 1). SECO and ENL, but not ENL-Gluc, decreased the IC 50 values of docetaxel in SKBR3 cells, while doxorubicin and carboplatin IC 50 values remain unchanged. The DRI values for docetaxel showed a concentration-dependent response, with 3.9-and 4.4-fold increase in cytotoxicity when combined with 50 mM SECO and ENL, respectively (Table 3). ...
Context 2
... solubility limited the maximum concentration of metformin (20 mM). When metformin was combined with 50 mM SECO and ENL, but not ENLGluc, significant decreases in cell viability were observed at metformin concentrations of 2.5, 5, and 10 mM with 50 mM SECO, while 50 mM ENL significantly reduced cell viability when combined with 0.3 mM metformin (Fig. ...
Context 3
... vitro studies have demonstrated that metformin induced cancer cell apoptosis via inhibition of FASN mRNA and protein expression, an effect observed only in the presence of lower glucose levels in cell culture (2.5 mM) (49,50). Studies have also shown that ENL can decrease FASN expression (51,52). Coincidentally, the breast cancer cell line, SKBR3, in this study was maintained in McCoy's 5a medium containing 15 mM glucose, while MDA-MB-231 cells were cultured in L-15 medium containing 5 mM galactose. ...
Citations
... It has been demonstrated by various studies that SDG exhibits protective effects against various cancers such as colon, prostate, and breast, with its antiproliferative, antioxidant, and anti-estrogenic properties and/or by inhibiting metabolic-related enzymes [2,10,[12][13][14]. There are more studies showing the anti-cancer treatment potential of the SDG metabolites enterodiol and enterolactone alone or in combination [7,8,15,16]. There are relatively few studies in the literature on the effects of SDG alone on cancer cells. ...
Objective: Lignans are important biologically active compounds in diphenolic structure. Secoisolariciresinol diglucoside (SDG) is a significant type of lignan known to have anti-cancer properties. This study aimed to investigate the antiproliferative activity properties of SDG on hepatocellular carcinoma cells (HepG2), colorectal cancer cells (DLD-1), lung carcinoma (A549), and prostate cancer (PC3) cell lines. Material and Method: Cell viability of cancer cells was determined by the MTT method after treatment with various concentrations of SDG at 48 or 72 hours. The DFT (Density Functional Theory) analysis of the SDG was performed using Spartan'10 and visualized. Drug-likeness and absorption, distribution, metabolism, excretion, and toxicity (ADME-Tox) properties of this compound were examined. Molecular docking was carried out to research the biological activity of SDG. Result and Discussion: Our results showed that SDG exhibited significant cytotoxicity only against DLD-1 cells with IC50 value of 37.45 µM, but inactive against other cancer cell lines as in vitro. 4UYA, which biomarker for colon cancer, is the crystal structure of the MLK4 kinase domain. The binding energy value for the SDG-MLK4 kinase domain was calculated as -6.1 kcal/mol. Anticancer potential was verified by in vitro assay and in silico molecular docking study. In conclusion, this study revealed the protective aspect of SDG against colon cancer and showed that it has promising anticancer activity.
... In addition, flaxseed lignans, by affecting connections in molecular signaling networks, modulate signaling cascades in various stages of cancer. Therefore, flaxseed lignans can inhibit the progression of various types of cancers [24,25]. ...
... Di et al. [25] investigated the effect of the combination of flaxseed lignans (SDG and ENL) and metformin with classic chemotherapeutic agents (docetaxel, doxorubicin, and carboplatin) on the cytotoxic effect of such drugs in the metastatic breast cancer cell lines (SKBR-3 and MDA-MB-231). Each cell line was divided into two groups. ...
Flaxseed contains high amounts of biologically active components such as α-linolenic acid, lignans, and dietary fiber. Due to its numerous nutritional properties, flaxseed has been classified as a "superfood", that is, a food of natural origin with various bioactive components and many health-promoting benefits. Flaxseed consumption can be an important factor in the prevention of diseases, particularly related to nutrition. The regular consumption of flaxseed may help to improve lipid profile and lower blood pressure, fasting glucose, and insulin resistance index (HOMA-IR). Moreover, flaxseed is characterized by anticancer and antioxidant properties and can significantly reduce the intensity of symptoms associated with menopause, constipation, and mental fatigue, improve skin condition, and accelerate wound healing. In addition to its bioactive compounds, flaxseed also contains antinutrients such as cyanogenic glycosides (CGs), cadmium, trypsin inhibitors, and phytic acid that can reduce the bioavailability of essential nutrients and/or limit its health-promoting effects. Three common forms of flaxseed available for human consumption include whole flaxseed, ground flaxseed, and flaxseed oil. The bioavailability of ALA and lignans is also dependent on the form of flaxseed consumed. To ensure high bioavailability of its bioactive components, flaxseed should be consumed in the ground form.
... Nevertheless, FLs have been considered as promising bioactive compounds with various health-benefitting properties such as antidiabetic, antioxidant, anticancer, anti-inflammatory and cardiovascular protective. 3,4 Particularly, FLs have been revealed to exhibit both chemopreventive and chemotherapeutic properties, 5,6 including the anticancer activity of synthetic SDG. The aim of the present work is to provide a superior comprehension of the anticancer molecular mechanisms of lignin and their metabolites by using both experimental in vivo and in vitro models. ...
Lignans are known dietary polyphenols found in cereals, plants and seeds. Flaxseed is one of the major sources of lignans mainly existing in the form of secoisolariciresinol diglucoside (SDG) which can be metabolised by the gut microbes into secoisolariciresinol (SECO) and mammalian lignan (enterodiol and enterolactone) that are easily absorbed through the intestines. Numerous studies reveal that flaxseed lignans (FLs) can be promising chemotherapeutics/chemopreventive agents. Their anticancer activity can occur through the induction of apoptosis, inhibition of cell proliferation, and the hindering of metastasis and angiogenesis. The anti-carcinogenesis of flaxseed lignans is achieved through multiple molecular mechanisms involving biochemical entities such as cellular kinases, cell cycle mediators, transcription factors, inflammatory cytokines, reactive oxygen species, and drug transporters. This review summarizes the bioavailability of FLs, their anticancer mechanisms in relevance to molecular targets, safety, and the scope of future research. Overall, FLs can be utilized in functional foods, dietary supplements, and pharmaceuticals for the management and prevention of cancers.
... The cytotoxicity of PFH-G9 against the ER-positive breast cell lines MCF7 and T47D was the most remarkable, with IC 50 values of 13.8 and 15.8 μg/ml, respectively (Ezzat et al. 2018).Furthermore, mice with 5% flaxseed in their diet had less growth and development of transgenic prostate cancer (Lin et al. 2002). In a study, it was investigated that, combining flaxseed lignans with traditional chemotherapeutic treatments like Docetaxel and Carboplatin greatly increased the cytotoxic effect of these medications against the metastatic breast cancer cell lines, SKBR3 and MDA-MB-231 (Di et al. 2018). Scherbakov et al. (2021) showed Secoisolariciresinol and Secoisolariciresinol-4′, 4″-diacetate to inhibit the MCF-7 cell lines with IC 50 values of 25 and 11 μM, respectively. ...
Lignans have long been known for their abundant therapeutic properties due to their polyphenolic structure. Linseed is the richest plant source of lignans and has been studied widely for their properties. The most prevalent lignan, secoisolariciresinol diglucoside (SDG), is consumed with linseed and converted into mammalian lignans, enterodiol (END) and enterolactone (ENL), by the gut microbiota. SDG can easily be assessed using HPLC and its deglycosylated form viz secoisolariciresinol can be asses using GC–MS techniques. Variety of extraction and analysis methods has been reported for plant lignans. SDG is known to have therapeutic properties including anti-oxidant, anti-cancerous, anti-inflammatory, modulation of gene expression, anti-diabetic, estrogenic and anti-estrogenic. Despite a large number of bioactivities, strong evidences for the underlying mechanisms for most of the properties are still unknown. SDG is most studied for its anti-cancerous properties. But the use of lignans as anti-carcinogenic agent is limited and commercially not reported due to challenges of purification at commercial level, rapid metabolism, untargeted delivery and toxic compounds associated with lignans. Exploration of more prominent and active derivatives of SDG and their targeted drug delivery should be an important research toward the use of bioactive lignans of linseed.
... This may be due to the increased lipophilicity of the compound, which facilitates its passage across the plasma membrane, or it may be due to the ability of the molecule to bind to lipophilic targets, such as ERs, which are expressed in MCF-7 cells (Lehraiki et al. 2010). Flaxseed lignans increased the cytotoxicity of chemotherapeutic agents on selected groups of breast cancer cells, and the combination of flaxseed lignans (SECO and EL) with commonly used chemotherapeutic drugs (docetaxel, doxorubicin and carboplatin), exhibits different mechanisms of therapeutic action by significantly increasing the chemotherapeutic capability to induce cytotoxicity in SKBR3 and MDA-MB-231 cancer cells (Di et al. 2018). ...
Flaxseed consumption (Linum usitatissimum L.) has increased due to its potential health benefits, such as protection against inflammation, diabetes, cancer, and cardiovascular diseases. However, flaxseeds also contains various anti-nutritive and toxic compounds such as cyanogenic glycosides, and phytic acids etc. In this case, the long-term consumption of flaxseed may pose health risks due to these non-nutritional substances, which may be life threatening if consumed in high doses, although if appropriately utilized these may prevent/treat various diseases by preventing/inhibiting and or reversing the toxicity induced by other compounds. Therefore, it is necessary to remove or suppress the harmful and anti-nutritive effects of flaxseeds before these are utilized for large-scale as food for human consumption. Interestingly, the toxic compounds of flaxseed also undergoes biochemical detoxification in the body, transforming into less toxic or inactive forms like α-ketoglutarate cyanohydrin etc. However, such detoxification is also a challenge for the development, scalability, and real-time quantification of these bioactive substances. This review focuses on the health affecting composition of flaxseed, along with health benefits and potential toxicity of its components, detoxification methods and mechanisms with evidence supported by animal and human studies.
... Likewise, in clinical trials, FS (25 g/day with 50 mg lignans for 32 days) supplementation suppressed tumor growth in breast cancer patients, whereas 50mg/day of lignans for a year reduced the risk in premenopausal women [203]. Further, FS lignans significantly sensitized SKBR3 and MDA-MB-231 breast cancer cell lines and enhanced the cytotoxic ability of chemotherapeutic agents such as docetaxel, doxorubicin, and carboplatin [204]. Secoisolariciresinol diglucoside (SDG) is an abundant lignan in FS with antiestrogenic activity in high estrogen environments. ...
... components enhance DOX cytotoxicity against breast cancer cell lines MDA-MB-231 and SKBR3 further increasing its translational impact [67]. Finally, a prospective randomized control trial is currently underway investigating the potential cardioprotective effects of flax 'milk' in women with breast cancer receiving cardiotoxic chemotherapy (ClinicalTrials. ...
While anthracyclines (ACs) are a class of chemotherapeutic agents that have improved the prognosis of many women with breast cancer, it is one of the most cardiotoxic agents used to treat cancer. Despite their reported dose-dependent cardiotoxicity, AC-based chemotherapy has become the mainstay of breast cancer therapy due to its efficacy. Elucidating the mechanisms of anthracycline-mediated cardiotoxicity and associated therapeutic interventions continue to be the main focus in the field of cardio-oncology. Herein, we summarized the current literature surrounding the mechanisms of anthracycline-induced cardiotoxicity, including the role of topoisomerase II inhibition, generation of reactive oxygen species, and elevations in free radicals. Furthermore, this review highlights the molecular mechanisms of potential cardioprotective interventions in this setting. The benefits of pharmaceuticals, including dexrazoxane, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, statins, and antioxidants in this setting, are reviewed. Finally, the mechanisms of emerging preventative interventions within this patient population including nutraceuticals and aerobic exercise are explored.
... They may also inhibit the activation of pre-carcinogens into electrophilic species and their subsequent interaction with DNA to prevent the occurrence of cancer [21]. For example, it can inhibit breast cancer growth and enhance chemotherapeutics' toxicity to tumors in vitro [22,23]. Lignans can be absorbed and metabolized by intestinal microflora into enterolactone. ...
Background: Some literature has studied the relationship between lignans intake and its metabolite, enterolactone, and breast cancer survival, but the results are far from consistent and conclusive. Therefore, we conducted a systematic review and meta-analysis in this situation.
Methods: From its inception to August 2020, we conducted a comprehensive search of PubMed, Embase, Web of Science, and Cochrane Library databases. This study reported the correlation between lignans intake and serum enterolactone concentrations and prognosis of breast carcinoma. The total hazard ratios (HRs) and 95% confidence interval (95% CI) were estimated, comparing the highest versus the lowest category of lignans intake and serum enterolactone concentrations, using a fixed or random-effects effect model.
Results: A total of 6 articles were included in reporting the all-cause mortality (ACM), breast cancer-specific mortality (BCSM), and recurrence of 2668, 1516, and 474 breast cancer patients in 18053 breast cancer patients. In postmenopausal women with breast cancer, lignans intake or enterolactone concentrations were associated with a reduced risk of all-cause mortality (maximum and minimum) (pooled HR = 0.73, 95% CI, 0.58-0.91), as was the association with breast cancer-specific mortality (maximum and minimum) (pooled HR = 0.72, 95% CI, 0.60, 0.87). Stratified analysis showed that exposure type and diagnosis time might be the sources of heterogeneity. In premenopausal women, the relationship seemed to be the opposite, showing an increased risk of all-cause mortality (maximum and minimum) in breast cancer patients (pooled HR = 1.57, 95% CI, 1.11-2.23). No significant association was found between lignans intake or enterolactone concentrations and breast cancer recurrence (pooled HR = 0.91, 95% CI, 0.69, 1.20).
Conclusion: This study provides limited evidence that lignans intake and higher serum enterolactone concentrations in postmenopausal women are beneficial to breast cancer patients' prognosis. In premenopausal women, however, the relationship may be reversed.
... Likewise, in clinical trials, FS (25 g/day with 50 mg lignans for 32 days) supplementation suppressed tumor growth in breast cancer patients, whereas 50mg/day of lignans for a year reduced the risk in premenopausal women [203]. Further, FS lignans significantly sensitized SKBR3 and MDA-MB-231 breast cancer cell lines and enhanced the cytotoxic ability of chemotherapeutic agents such as docetaxel, doxorubicin, and carboplatin [204]. Secoisolariciresinol diglucoside (SDG) is an abundant lignan in FS with antiestrogenic activity in high estrogen environments. ...
Breast cancer is one of the leading causes of death in humans worldwide and is the most common type of cancer in women. Several factors are responsible for the development of breast cancer in women. Disturbances in various molecular pathways and the concomitant altered expression of several molecular markers have been well reported. Despite the potent beneficial effects of various therapeutic strategies such as surgery, chemotherapy, and radiotherapy, the associated detrimental side effects of these strategies has spurred the scientific community to search for alternatives. Phytotherapy is one such potential therapeutic strategy involving the usage of traditional medicinal plants to target various molecular markers altered during cancer and thereby to protect from cancer without inducing side effects. In this chapter we explain the possible beneficial effects of a few traditional Indian medical plants against breast cancer.
... Araştırmalar, SDG'nin MDA-MB-231 meme kanseri hücre hattında proliferasyonu, adhezyonu, migrasyonu ve invazyonu azalttığını göstermekte ve bu hücrelerin radyasyona ve kemoterapiye yanıtını arttırdığını belirtmektedir(Bigdeli et al., 2016;Chen & Thompson, 2003;Di, De Silva, Krol, & Alcorn, 2018;Lindahl, Saarinen, Abrahamsson, & Dabrosin, 2011;Saarinen et al., 2010; Xiong et al., 2015). Ancak bu etkilerin oluşumunda hangi moleküler mekanizmaların sorumlu olduğu henüz tam olarak açıklanamamıştır SDG'nin bazı yararlı etkileri, antioksidan özelliği ile ilişkili bulunmaktadır. ...
Despite many advances in food sanitation techniques, foodborne diseases remain as one of the
major causes of death worldwide. Traditional antimicrobial methods not only reduce the
microbial population in foods to a varying extent, but damage the beneficial microorganisms
found naturally in foods. Increasing number of foodborne outbreaks due to the pathogens
resistant to antibiotics also require novel strategies. Although novel food processing
technologies (pulsed electric field, high pressure applications, ultrasound, plasma treatment,
and irradiation) are prominent processes in preventing bacterial contamination and bacteria
multiplication in food, they are extremely costly and time consuming processes. Alternatively,
the use of bacteriophages as biocontrol agents in food safety is attracting attention as a cheap
and fast method. Phages are viruses that infect bacterial cells only and harmless to humans,
animals, and plants. Phages are categorized as lytic or lysogenic based on their life cycles.
Lytic phages have various potential applications as biocontrol agents in the food industry.
Phage products developed for the main pathogenic bacteria that cause foodborne diseases
have been used as antimicrobial agents on foods by obtaining GRAS (Generally Recognized
As Safe) status and FDA approval. Phages have also been proposed as an alternative to
antibiotics in animal health. The use of phages as an alternative method in food industry and
health is today a popular topic that is gaining importance. In this report, it is aimed to provide
an overview of the use of phages as biocontrol agents against foodborne pathogens and to
provide up-to-date information on the common use of phages in food safety.
Keywords: Bacteriophage, phage, pathogens, food safety
