Abstract
Cancer is one of the leading causes of death globally. The development of drug resistance is the main contributor to cancer-related mortality. Cancer cells exploit multiple mechanisms to reduce the therapeutic effects of anticancer drugs, thereby causing chemotherapy failure. Natural products are accessible, inexpensive, and less toxic sources of chemotherapeutic agents. Additionally, they have multiple mechanisms of action to inhibit various targets involved in the development of drug resistance. In this review, we have summarized the basic research and clinical applications of natural products as possible inhibitors for drug resistance in cancer. The molecular targets and the mechanisms of action of each natural product are also explained. Diverse drug resistance biomarkers were sensitive to natural products. P-glycoprotein and breast cancer resistance protein can be targeted by a large number of natural products. On the other hand, protein kinase C and topoisomerases were less sensitive to most of the studied natural products. The studies discussed in this review will provide a solid ground for scientists to explore the possible use of natural products in combination anticancer therapies to overcome drug resistance by targeting multiple drug resistance mechanisms.
Highlights
Cancer is the second most common cause of death after cardiovascular diseases
Previous studies on cell lines and animal models revealed that drug resistance in cancer can be achieved by complex mechanisms, including drug efflux using adenosine triphosphate (ATP)-binding cassette (ABC) transporter [5], altering the expression of proteins targeted by anticancer drugs [6], drug detoxification [7], augmenting repair mechanisms in DNA [8], and evasion of apoptosis [1]
We summarize natural products that have the potential to overcome drug resistance in cancer
Summary
Cancer is the second most common cause of death after cardiovascular diseases. Statistics from the USA showed that the number of people diagnosed with cancer was 1.7 million in 2017 with 0.6 million deaths [1]. Ninety percent of deaths from cancer result from the development of drug resistance, which leads to the ineffectiveness of chemotherapeutic agents [2]. In some types of cancer such as renal cancer and hepatocellular carcinoma, malignant cells start resistance without previous exposure to chemotherapeutic agents (intrinsic resistance) resulting in a poor response to initial treatment [4]. Extensive research was conducted to explore the potential of natural products in cancer therapy. These efforts resulted in the development of some effective drugs derived from natural phytochemicals [10]. We summarize natural products that have the potential to overcome drug resistance in cancer. I1ll.uIsltlruastitornatoifodnruogfcdhreumgorcehsiestmanocreemsiescthaanncisemms iencchaannceisrmcesllsin[1]c.aAnBcCe:rAcTePllbsin[1d]i.ngAcBaCss:etAteT, RPTKb:inredcienpgtor tycraosssientetkei,nRasTeK, T:KrIe:ctyerpotsoinretkyirnoassieninehkibinitaorsse., TKI: tyrosine kinase inhibitors
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