Imperatorin as a Promising Chemotherapeutic Agent against Human Larynx Cancer and Rhabdomyosarcoma Cells

Abstract

Naturally occurring coumarins are bioactive compounds widely used in Asian traditional medicine. They have been shown to inhibit proliferation, induce apoptosis, and/or enhance the cytotoxicity of currently used drugs against a variety of cancer cell types. The aim of our study was to examine the antiproliferative activity of different linear furanocoumarins on human rhabdomyosarcoma, lung, and larynx cancer cell lines, and dissolve their cellular mechanism of action. The coumarins were isolated from fruits of Angelica archangelica L. or Pastinaca sativa L., and separated using high-performance counter-current chromatography (HPCCC). The identity and purity of isolated compounds were confirmed by HPLC-DAD and NMR analyses. Cell viability and toxicity assessments were performed by means of methylthiazolyldiphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, respectively. Induction of apoptosis and cell cycle progression were measured using flow cytometry analysis. qPCR method was applied to detect changes in gene expression. Linear furanocoumarins in a dose-dependent manner inhibited proliferation of cancer cells with diverse activity regarding compounds and cancer cell type specificity. Imperatorin (IMP) exhibited the most potent growth inhibitory effects against human rhabdomyosarcoma and larynx cancer cell lines owing to inhibition of the cell cycle progression connected with specific changes in gene expression, including CDKN1A. As there are no specific chemotherapy treatments dedicated to laryngeal squamous cell carcinoma and rhabdomyosarcoma, and IMP seems to be non-toxic for normal cells, our results could open a new direction in the search for effective anti-cancer agents.

Synergy, Additivity, and Antagonism between Cisplatin and Selected Coumarins in Human Melanoma Cells

“…Additionally, naturally occurring compounds often attenuate CDDP toxicity through their antioxidant and anti-inflammatory effects [ 22 ]. Considering the molecular mechanism(s) of action of the most promising combination of CDDP and OST, it should be stressed that the antitumor activity of coumarins is mainly related to the induction of apoptosis through the caspase-dependent mechanism [ 58 ]. As regards OST, it was observed that the drug produced upregulation of the ratio of Bax/Bcl-2 proteins and inhibited Akt kinase activity [ 59 ].…”

“…It should be stressed that in this study, we did not determine the cytotoxicity of the tested coumarins on normal (healthy) cells. However, some reports revealed that IMP, ISO, XIN, XOL, and OST do not exert cytotoxic effects on normal skin cells [ 58 , 59 ]. Thus, it can be assumed that combination of OST with CDDP can enhance the cytotoxic effect of the latter drug.…”

Direct Targeting of CREB1 with Imperatorin Inhibits TGFβ2‐ERK Signaling to Suppress Esophageal Cancer Metastasis

“…For example, imperatorin has been reported as a potential chemotherapeutic agent in human larynx cancer. [24] Another study showed that imperatorin could suppress drug-resistant liver cancer through inducing Mcl-1 degradation to cooperatively trigger Bax translocation and Bak activation. [12] However, most of the studies focus on the function of imperatorin in chemoresistance, we provide the first evidence suggesting the potential of imperatorin in suppressing tumor invasion and metastasis.…”

Magnoflorine—Isolation and the Anticancer Potential against NCI-H1299 Lung, MDA-MB-468 Breast, T98G Glioma, and TE671 Rhabdomyosarcoma Cancer Cells

“…Despite significant advances in cancer therapy, patient survival rates are still low. The inadequate efficacy of standard anti-cancer therapies and their serious side effects led to a renewed interest in natural medicine to identify bioactive compounds of plant origin with promising chemotherapeutic properties [ 30 ]. MGN, a quaternary aporphine alkaloid widely distributed in many species of plants, seems to be a promising active agent with potential anti-cancer properties.…”