Reversal of Multidrug Resistance in Cancer by Multi-Functional Flavonoids

Abstract

Multidrug resistance (MDR) resulting from different defensive mechanisms in cancer is one of the major obstacles of clinical treatment. To circumvent MDR many reversal agents have been developed, but most of them fail in clinical trials due to severely adverse effects. Recently, certain natural products have been reported to overcome MDR, including flavonoids which are abundant in plants, foods, and herbs. The structure of flavonoids can be abbreviated as C6-C3-C6 (C for carbon), and further categorized into flavonoids, iso-flavonoids and neo-flavonoids, according to their structural backbones. Flavonoids possess multiple bioactivities, and a growing body of research has indicated that both flavonoids and iso-flavonoids can either kill or re-sensitize conventional chemotherapeutics to resistant cancer cells. Here, we summarize the research and discuss the underlying mechanisms, concluding that these flavonoids do not function as specific regulators of target proteins, but rather as multi-functional agents that negatively regulate the key factors contributing to MDR.

A trimethoxy flavonoid isolated from stem extract of Tabebuia chrysantha suppresses angiogenesis in angiosarcoma

“…[ 25 ] Researchers reported that flavonoids and iso‐flavonoids possess multiple bioactivities and can either kill or resensitise conventional chemotherapeutics to resistant cancer cells. [ 26 ] So we are in search of a novel angiosarcoma‐targeting agent that has minimal side effects and null tumour resistance nature and can be suitable for old patients with angiosarcoma.…”

Alleviation of Multidrug Resistance by Flavonoid and Non-Flavonoid Compounds in Breast, Lung, Colorectal and Prostate Cancer

“…Due to toxicity and lack of specificity of synthetic MDR agents, recent researches have focused on beneficial effects of natural compounds in overcoming MDR in cancer. According to recent research, polyphenols might overcome MDR through various mechanisms, which will be further discussed in our work [32][33][34][35].…”

Synthesis and Anticancer Cytotoxicity of Azaaurones Overcoming Multidrug Resistance

“…For each azaaurone, carbon, hydrogen, and nitrogen atoms were analyzed and were found in nearly full (96-98%) agreement with the expected values. The compounds were fully characterized by 1 H NMR, 13 C NMR, and high-resolution mass spectrometry (HRMS) (data shown in Supplementary Materials, Table S5).…”

“…We screened a library of 140 compounds consisting of flavonoidic derivatives and thiosemicarbazones (Figure 1, full structures are provided in Supplementary Materials, Table S1). Flavonoidic derivatives have been widely studied as candidates for cancer treatment and prevention, with various naturally occurring substances reported to be effective against resistant tumors [13,14]. On the other hand, thiosemicarbazones were included since several compounds belonging to this class have been reported to possess increased toxicity against otherwise drug-resistant cells [15][16][17][18].…”