Marine Natural Products as Models to Circumvent Multidrug Resistance

Long, Solida; Sousa, Emı́lia; Kijjoa, Anake; Pinto, Madalena

doi:10.3390/molecules21070892

Cited by 33 publications

(29 citation statements)

References 224 publications

(341 reference statements)

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“…The P-gp inhibitory activity of natural marine compounds including Ningalin B and terpenoids was comprehensively summarized in the review article by Long et al [ 43 ]. Ningalin B is a natural marine product isolated from the ascidian (sea squirt) family of the genus Didemnum [ 44 , 45 , 46 ].…”

Section: Abcb1/p-gpmentioning

confidence: 99%

The Effects of Synthetically Modified Natural Compounds on ABC Transporters

et al. 2018

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Multidrug resistance (MDR) is a major hurdle which must be overcome to effectively treat cancer. ATP-binding cassette transporters (ABC transporters) play pivotal roles in drug absorption and disposition, and overexpression of ABC transporters has been shown to attenuate cellular/tissue drug accumulation and thus increase MDR across a variety of cancers. Overcoming MDR is one desired approach to improving the survival rate of patients. To date, a number of modulators have been identified which block the function and/or decrease the expression of ABC transporters, thereby restoring the efficacy of a range of anticancer drugs. However, clinical MDR reversal agents have thus far proven ineffective and/or toxic. The need for new, effective, well-tolerated and nontoxic compounds has led to the development of natural compounds and their derivatives to ameliorate MDR. This review evaluates whether synthetically modifying natural compounds is a viable strategy to generate potent, nontoxic, ABC transporter inhibitors which may potentially reverse MDR.

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Section: Abcb1/p-gpmentioning

confidence: 99%

The Effects of Synthetically Modified Natural Compounds on ABC Transporters

et al. 2018

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“…Indeed, fish oils are marine-derived products that have been in use for millennia. Actually, several reviews on this topic have been published [52,53,54,55,56,57,58]. Different marines organisms (from fishes such as salmon and herring, to krill and squid) contain so-called “marine ω-3 fatty acids” and specifically eicosapentaenoic acid (EPA; 20:5 n -3), docosapentaenoic acid (DPA; 22:5 n -3) and docosahexaenoic acid (DHA; 22:6 n -3) [59].…”

Section: Treatment Of Obesitymentioning

confidence: 99%

Metabolic Disorder in Chronic Obstructive Pulmonary Disease (COPD) Patients: Towards a Personalized Approach Using Marine Drug Derivatives

et al. 2017

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Metabolic disorder has been frequently observed in chronic obstructive pulmonary disease (COPD) patients. However, the exact correlation between obesity, which is a complex metabolic disorder, and COPD remains controversial. The current study summarizes a variety of drugs from marine sources that have anti-obesity effects and proposed potential mechanisms by which lung function can be modulated with the anti-obesity activity. Considering the similar mechanism, such as inflammation, shared between obesity and COPD, the study suggests that marine derivatives that act on the adipose tissues to reduce inflammation may provide beneficial therapeutic effects in COPD subjects with high body mass index (BMI).

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“…Drug-resistance in cancer cells develops as a result of numerous different mechanisms, of which understanding has improved owing to the use of novel research techniques. These mechanisms include the lowering of the intracellular drug concentration, activation of detoxification enzymes, changes in drug metabolism inside of the cell and the inhibition of cancer cell apoptosis (33,34). The most well-known and frequently described MDR mechanism is the increased expression of transport proteins at the membrane of cancer cells (35).…”

Section: Discussionmentioning

confidence: 99%

Expression of genes and proteins of multidrug resistance in gastric cancer cells treated with resveratrol

et al. 2018

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Abstract. Multidrug resistance (MDR) is a notable problem in the use of chemotherapy. Therefore, studies aimed at identifying substances capable of overcoming resistance of cancer cells are required. Examples of these compounds are polyphenols, including resveratrol, that exert a range of various biological activities. The aim of the present study was to demonstrate the effect of 3,5,4'-trihydroxy-trans-stilbene (resveratrol) on the expression of ATP binding cassette subfamily B member 1, Annexin A1 (ANXA1) and thioredoxin (TXN) genes, and the proteins encoded by these genes, which are associated with MDR. The experiments were performed in human gastric cancer cell lines EPG85-257RDB (RDB) and EPG85-257RNOV (RNOV), which are resistant to daunorubicin and mitoxantrone, respectively, in addition to EPG85-257P (control), which is sensitive to cytostatic drugs. Cells were treated with 30 or 50 µM resveratrol for 72 h and changes in the expression levels of the genes were analysed with the use of a reverse transcription-quantitative polymerase chain reaction. The cellular levels of P-glycoprotein (P-gp), ANXA1 and TXN were evaluated using immunofluorescence and western blot analysis. Resveratrol in both concentrations has been shown to have a statistically significant influence on expression of the mentioned genes, compared with untreated cells. In RDB cells, resveratrol reduced the expression level of all analyzed genes, compared with untreated cells. Similar results at the protein level were obtained for P-gp and TXN. In turn, in the RNOV cell line, resveratrol reduced TXN expression at mRNA and protein levels, compared with untreated cells. The results of the present study indicate that resveratrol may reduce the resistance of cancer cells by affecting the expression of a number of the genes and proteins associated with MDR. IntroductionResveratrol belongs to the stilbenoid group of polyphenols, possessing two phenol rings linked to each other by an ethylene bridge (1). In 1940, resveratrol was isolated from the root of Veratrum grandiflorum (1,2). A primary dietary source of resveratrol is red wine, as a very high resveratrol concentration is present in the skin of red grapes (50-100 µg/g) (3). In natural conditions, resveratrol is synthesized by plants in response to external environmental factors, including ultraviolet radiation and heavy metals (3,4). Resveratrol is identified in two isomeric forms, cis and trans-resveratrol ( Fig. 1) (5,6).The trans form is dominant in terms of its prevalence and biological activity (7). The hydrophobic nature of resveratrol considerably contributes to its limited bioavailability (8).Owing to the varied biological activity of resveratrol, it has been the subject of numerous studies aimed at revealing its health-enhancing properties, and its use in prevention and treatment of many diseases (1,3,5,9). The results of in vitro and in vivo studies have proved that resveratrol exhibits anticancer activity at all three stages of the oncogenic process: initiation, promotion and progr...

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Marine Natural Products as Models to Circumvent Multidrug Resistance

Cited by 33 publications

References 224 publications

The Effects of Synthetically Modified Natural Compounds on ABC Transporters

The Effects of Synthetically Modified Natural Compounds on ABC Transporters

Metabolic Disorder in Chronic Obstructive Pulmonary Disease (COPD) Patients: Towards a Personalized Approach Using Marine Drug Derivatives

Expression of genes and proteins of multidrug resistance in gastric cancer cells treated with resveratrol

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