Studies on Coumarins and Coumarin-Related Compounds to Determine their Therapeutic Role in the Treatment of Cancer

Abstract

The Benzopyrones are a group of compounds whose members include coumarins and flavonoids. Dietary exposure to benzopyrones is quite significant, as these compounds are found in vegetables, fruit, seeds, nuts, coffee, tea and wine. It is estimated that the average western diet contains approximately 1 g/day of mixed benzopyrones. It is, therefore, not difficult to see why extensive research into their pharmacological and therapeutic properties is underway over many years. Coumarin is a natural substance that has shown anti-tumour activity in vivo, with the effect believed to be due to its metabolites (e.g. 7-hydroxycoumarin). This review is based on recent studies of coumarins and coumarin related compounds. Therefore, the focus will be on these relevant compounds and their therapeutic importance. A recent study has shown that 7-hydroxycoumarin inhibits the release of Cyclin D1, which is overexpressed in many types of cancer. This knowledge may lead to its use in cancer therapy. Esculetin inhibits growth and cell cycle progression by inducing arrest of the G(1) phase in HL-60 leukaemia cells, resulting from the inhibition of retinoblastoma protein phosphorylation. Recent studies investigating the potential of flavonoids as therapeutic agents have suggested they may have use in various therapeutic settings ranging from leukaemia treatment to the treatment of patients with HIV. Genistein is a well-known isoflavone and is a tyrosine kinase inhibitor. Studies have indicated that genistein elicits inhibitory effects on cell growth of various carcinoma cell-lines and may be a potential candidate for cancer therapy. In our research, we have investigated the effects of coumarins and coumarin-related compounds on a panel of cell-lines. The most recent work involves two cell-lines, MCF-7 a breast carcinoma and A549 a lung carcinoma. Microtitre assays were performed along with real-time analysis of cell viability using a biosensor called the Cytosensor microphysiometer. These studies suggest that both genistein and esculetin exerted the most potent inhibitory effect on cell growth in comparison to the other two compounds.

Potential antiproliferative effect of isoxazolo- and thiazolo coumarin derivatives on breast cancer mediated bone and lung metastases

“…Some coumarins display cytostatic properties while others have cytotoxic activities (2). Their inhibitory eff ect on cell proliferation was confi rmed in various carcinoma cell lines, including those of melanoma, leukaemia, renal carcinoma, prostate and breast cancer (1,(3)(4)(5). This activity was further validated by other investigators in human subjects as well (6,7).…”

“…The reagents used for this purpose include DNA intercalating agents, topoisomerase inhibitors, cytoskeleton-disrupting agents and antimetabolites. Among these coumarin and coumarin-related compounds, members of the benzo-α-pyrone family, have been proven to exert antitumour eff ects and cause signifi cant changes in the regulation of immune responses, cell growth and diff erentiation (1). Antitumour activity is believed to be due to coumarin metabolites (e.g., 7-hydroxycoumarin).…”

Natural Polyphenols that Display Anticancer Properties through Inhibition of Kinase Activity

“…Later, many other types of biological activities were discovered ranging from photosensitization to vasodilatation. Coumarin derivatives reported to exert anticancer activity through kinase targeting include esculetin (36), scopoletin (37) and daphnetin (38, Table 4) [77][78][79][80].…”

“…Esculetin (36) has been shown to induce apoptosis in various human cancer cells [77] and, more particularly, U937 human leukemia cells [78]. This anticancer activity was associated with selective activation of the phosphorylation of extracellular-regulated kinase (ERK) and c-Jun Nterminal kinase (JNK) [78].…”

Phytochemical Screening of Medicinal Plants of the Kakamega Country, Kenya Commonly Used against Cancer

“…A recent study has shown that 7-hydroxycoumarin inhibited the release of cyclin D1, which is overexpressed in many cancer types [13]. Many compounds derived from coumarin have numerous therapeutic applications, which include photochemotherapy, antitumor and anti-HIV therapy [14].…”