Targeting Drug Chemo-Resistance in Cancer Using Natural Products

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.

Keywords: anticancer natural products; drug detoxification; drug efflux; plants derived natural products.

Figure 1

Illustration of drug chemoresistance mechanisms in cancer cells [1]. ABC: ATP binding cassette, RTK: receptor tyrosine kinase, TKI: tyrosine kinase inhibitors.

Figure 2

Summary of the main natural compounds targeting multidrug resistance biomarkers in cancer.

Figure 3

Natural products mechanism of action in promoting non-apoptotic cell death in cancer cells. RIPK1, receptor-interacting serine/threonine-protein kinase 1; MLKL, mixed lineage kinase domain-like; ROS, reactive species; TNF-α, tumor necrosis factor; ATG5, autophagy related 5; LC-II, light chain 2; STIM1, stromal interaction molecule 1; AKT, protein kinase B; mTOR, mammalian target of rapamycin; AMPK, AMP-activated protein kinase; HIF-1, hypoxia-inducible factor-1; BECN1, beclin1; NF-kB, nuclear factor kappa B.