Phytochemicals: Potential Lead Molecules for MDR Reversal
Boshra Tinoush1, Iman Shirdel2, Michael Wink1
1Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany.
Abstract:
Multidrug resistance (MDR) is one of the main impediments in the treatment of cancers. MDR cancer cells are resistant to multiple anticancer drugs. One of the major mechanisms of MDR is the efflux of anticancer drugs by ABC transporters. Increased activity and overexpression of these transporters are important causes of drug efflux and, therefore, resistance to cancer chemotherapy. Overcoming MDR is a fundamental prerequisite for developing an efficient treatment of cancer. To date, various types of ABC transporter inhibitors have been employed but no effective anticancer drug is available at present, which can completely overcome MDR. Phytochemicals can reverse MDR in cancer cells via affecting the expression or activity of ABC transporters, and also through exerting synergistic interactions with anticancer drugs by addressing additional molecular targets. We have listed numerous phytochemicals which can affect the expression and activity of ABC transporters in MDR cancer cell lines. Phytochemicals in the groups of flavonoids, alkaloids, terpenes, carotenoids, stilbenoids, lignans, polyketides, and curcuminoids have been examined for MDR-reversing activity. The use of MDR-reversing phytochemicals with low toxicity to human in combination with effective anticancer agents may result in successful treatment of chemotherapy-resistant cancer. In this review, we summarize and discuss published evidence for natural products with MDR modulation abilities.
Insights
Multidrug resistance (MDR) in cancer is a major treatment challenge. This review highlights phytochemicals that can reverse MDR by modulating ABC transporters, offering potential for improved cancer chemotherapy.
Area of Science:
- Oncology
- Pharmacology
- Natural Products Chemistry
Background:
- Multidrug resistance (MDR) significantly impedes effective cancer chemotherapy.
- ATP-binding cassette (ABC) transporters are key mediators of MDR through drug efflux.
- Current MDR treatments are insufficient, necessitating novel therapeutic strategies.
Purpose of the Study:
- To review and discuss natural products, specifically phytochemicals, with MDR-reversing capabilities.
- To explore the mechanisms by which phytochemicals modulate ABC transporter activity and expression.
- To identify phytochemical classes with potential for combination therapy in resistant cancers.
Main Methods:
- Comprehensive literature search for studies on phytochemicals and MDR.
- Categorization of phytochemicals based on chemical structure (e.g., flavonoids, alkaloids, terpenes).
- Analysis of evidence for MDR modulation via ABC transporter interaction and synergistic effects.
Main Results:
- Numerous phytochemicals from various classes demonstrate MDR-reversing activity in cancer cell lines.
- Phytochemicals impact ABC transporter expression and/or function, reducing drug efflux.
- Synergistic interactions between phytochemicals and conventional anticancer drugs are observed.
Conclusions:
- Phytochemicals represent a promising avenue for overcoming MDR in cancer treatment.
- Combination therapy using low-toxicity phytochemicals with anticancer agents may enhance treatment efficacy.
- Further research into phytochemical mechanisms and clinical application is warranted.
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