Antiproliferative Activity of Flavonoids: Influence of the Sequential Methoxylation State of the Flavonoid Structure

Abstract

Dracocephalum kotschyi Boiss. has been used as part of an ethnobotanical remedy against many forms of human cancer in Iran. It has been demonstrated that a flavonoid named xanthomicrol from D. kotschyi contributes to its preferential antiproliferative activity against malignant cells. In the present study, the antiproliferative activity of its flavonoid fraction was further characterized. Using liquid-liquid extraction and a semi-preparative reversed-phase HPLC method, eight flavonoid aglycones were isolated from the aerial parts of the plant and their identities were confirmed through MS and NMR analyses as luteolin, naringenin, apigenin, isokaempferide, cirsimaritin, penduletin, xanthomicrol and calycopterin. The in vitro antiproliferative activity of each compound was evaluated against a panel of established normal and malignant cell lines using the MTT assay and some structure-activity relationships were observed. The hydroxyflavones (luteolin, apigenin and isokaempferide) exerted comparable antiproliferative activities against malignant and normal cells, while the methoxylated hydroxyflavones (cirsimaritin, penduletin, xanthomicrol and calycopterin) showed preferential activities against tumor cells. This activity may be of value in treating tumors as it would exert few side effects in normal tissues. Xanthomicrol selectively inhibited the growth of human gastric adenocarcinoma, while calycopterin selectively prevented human acute promyelocytic leukemia and human colon carcinoma cells proliferation.

Overproduction of valuable methoxylated flavones in induced tetraploid plants of Dracocephalum kotschyi Boiss

“…Recent pharmacological studies have confirmed presence of several methoxylated flavonoids with anti-cancer properties (Jahaniani et al 2005;Moghaddam et al 2012) and inhibitory effects on the lectin-induced cellular immune response in this plant (Faham et al 2008). Its leaf extract has been reported to have antihyperlipidemic (Ebrahim Sajjadi et al 1998), immunomodulatory (Amirghofran et al 2000), antinociceptive (Golshani et al 2004) and cytotoxic (Jahaniani et al 2005) effects.…”

“…This diversity of structural patterns has made flavonoids a rich source of compounds with potential anticancer properties. Recent pharmacological studies suggested some methoxylated flavonoids (Xanthomicrol and Calycopterin) of D. kotschyi with anti-cancer properties (Jahaniani et al 2005;Moghaddam et al 2012).…”

Dracocephalum: Novel Anticancer Plant Acting on Liver Cancer Cell Mitochondria

“…The extract was filtered and dried. Then 0.5 g dried extract was reconstituted in 2 mL DMSO for our mitochondrial experiments [13]. For standardization process the amounts of the eight flavonoids were measured in this extract.…”

Characterization of Natural Aryl Hydrocarbon Receptor Agonists from Cassia Seed and Rosemary

“…In the present study, nepitrin (15) and homoplantagenin (16), which are flavone glucosides, were found to have noticeable AhR activity. (14) [17], and nepitrin (15) has been reported to have anti-inflammatory and gastroprotective activity [18,19]. Recently, several studies have reported that activation of AhR may be involved in various immune responses as described above; therefore, natural AhR ligands are expected to have beneficial regulatory roles in humans, mediating anti-allergy and anti-cancer effects.…”