Xanthomicrol Activity in Cancer HeLa Cells: Comparison with Other Natural Methoxylated Flavones

Abstract

The methoxylated flavone xanthomicrol represents an uncommon active phenolic compound identified in herbs/plants with a long application in traditional medicine. It was isolated from a sample of Achillea erba-rotta subsp. moschata (musk yar-row) flowering tops. Xanthomicrol promising biological properties include antioxidant, anti-inflammatory, antimicrobial, and anticancer activities. This study mainly focused on the evaluation of the xanthomicrol impact on lipid metabolism in cancer HeLa cells, together with the investigation of the treatment-induced changes in cell growth, morphology, and apoptosis. At the dose range of 5–100 μM, xanthomicrol (24 h of incubation) significantly reduced viability and modulated lipid profile in cancer Hela cells. It induced marked changes in the phospholipid/cholesterol ratio, significant decreases in the levels of oleic and palmitic acids, and a marked increase of stearic acid, involving an inhibitory effect on de novo lipogenesis and desaturation in cancer cells. Moreover, marked cell morphological alterations, signs of apoptosis, and cell cycle arrest at the G2/M phase were observed in cancer treated cells. The bioactivity profile of xanthomicrol was compared to that of the anticancer methoxylated flavones eupatilin and artemetin, and structure–activity relationships were underlined.

Comparative Evaluation of Anticancer Activity of Natural Methoxylated Flavones Xanthomicrol and Eupatilin in A375 Skin Melanoma Cells

“…The O-methylated flavones eupatilin (5,7-dihydroxy-3′,4′,6-trimethoxyflavone) (EUP, 2) and xanthomicrol (5,4′-dihydroxy-6,7,8-trimethoxyflavone) (XAN, 3) are naturally occurring pharmacologically active compounds ( Figure 1 ) [ 13 , 14 ].…”

“…This phenol has been indicated as a potential therapeutic/chemopreventive agent for the treatment of different types of cancer [ 18 ]. The main mechanisms of EUP antitumor activity include the inhibition of cancer cell growth and proliferation [ 13 , 18 , 22 , 23 , 24 , 25 ], induction of apoptosis [ 13 , 18 , 24 ] cell differentiation [ 25 ], cell cycle arrest [ 14 , 22 , 23 , 25 ], mitochondria membrane potential reduction [ 13 , 18 ], alteration of cytoskeletal organization [ 26 ], and modulation of cancer cell signaling pathways [ 18 , 22 , 23 , 24 ]. Moreover, its anticancer activity has been reported to be mediated through its prooxidant activity [ 18 ].…”

“…This methoxylated flavone is a bioactive compound present in several plants and herbs with a long application in traditional medicine, such as Varthemia iphionoides , Achillea erba-rotta subsp. moschata (Wulfen) I. Richardson, Clinopodium douglasii , Dracocephalum kotschyi Boiss, Baccharis pentlandii D.C., Baccharis densiflora Wedd, Ocimum gratissimum L., and Artemisia campestris L. [ 9 , 14 , 27 , 28 , 29 , 30 ]. XAN has antioxidant [ 9 ], antimicrobial [ 9 ], anti-inflammatory [ 9 ], and anticancer properties [ 9 , 14 , 27 , 28 , 29 , 30 ].…”

“…moschata (Wulfen) I. Richardson, Clinopodium douglasii , Dracocephalum kotschyi Boiss, Baccharis pentlandii D.C., Baccharis densiflora Wedd, Ocimum gratissimum L., and Artemisia campestris L. [ 9 , 14 , 27 , 28 , 29 , 30 ]. XAN has antioxidant [ 9 ], antimicrobial [ 9 ], anti-inflammatory [ 9 ], and anticancer properties [ 9 , 14 , 27 , 28 , 29 , 30 ]. The XAN antitumor properties are linked to its capacity to inhibit the proliferation and viability in cancer cells [ 9 , 14 , 27 , 28 , 29 ], angiogenesis [ 27 ], cancer-related enzymes [ 27 , 30 ], and to induce apoptosis [ 9 , 14 , 27 , 30 ] and cell cycle arrest [ 9 , 14 , 27 , 30 ].…”

“…XAN has antioxidant [ 9 ], antimicrobial [ 9 ], anti-inflammatory [ 9 ], and anticancer properties [ 9 , 14 , 27 , 28 , 29 , 30 ]. The XAN antitumor properties are linked to its capacity to inhibit the proliferation and viability in cancer cells [ 9 , 14 , 27 , 28 , 29 ], angiogenesis [ 27 ], cancer-related enzymes [ 27 , 30 ], and to induce apoptosis [ 9 , 14 , 27 , 30 ] and cell cycle arrest [ 9 , 14 , 27 , 30 ].…”