Anti-Neoplastic Activity of Two Flavone Isomers Derived from Gnaphalium elegans and Achyrocline bogotensis

Christan M Thomas,Ruben D Torrenegra,Jarrett E Wyatt,Maria Ballester,Robert C Wood,Victoria P Ramsauer,Morgan H Pendleton,Oscar E Rodriguez,Sam Harirforoosh,Koyamangalath Krishnan,Janet Lightner,Kamyar Afarinkia

doi:10.1371/journal.pone.0039806

Abstract

Over 4000 flavonoids have been identified so far and among these, many are known to have antitumor activities. The basis of the relationships between chemical structures, type and position of substituent groups and the effects these compounds exert specifically on cancer cells are not completely elucidated. Here we report the differential cytotoxic effects of two flavone isomers on human cancer cells from breast (MCF7, SK-BR-3), colon (Caco-2, HCT116), pancreas (MIA PaCa, Panc 28), and prostate (PC3, LNCaP) that vary in differentiation status and tumorigenic potential. These flavones are derived from plants of the family Asteraceae, genera Gnaphalium and Achyrocline reputed to have anti-cancer properties. Our studies indicate that 5,7-dihydroxy-3,6,8-trimethoxy-2-phenyl-4H-chromen-4-one (5,7-dihydroxy-3,6,8-trimethoxy flavone) displays potent activity against more differentiated carcinomas of the colon (Caco-2), and pancreas (Panc28), whereas 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H-chromen-4-one (3,5-dihydroxy-6,7,8-trimethoxy flavone) cytototoxic action is observed on poorly differentiated carcinomas of the colon (HCT116), pancreas (Mia PaCa), and breast (SK-BR3). Both flavones induced cell death (>50%) as proven by MTT cell viability assay in these cancer cell lines, all of which are regarded as highly tumorigenic. At the concentrations studied (5–80 µM), neither flavone demonstrated activity against the less tumorigenic cell lines, breast cancer MCF-7 cells, androgen-responsive LNCaP human prostate cancer line, and androgen-unresponsive PC3 prostate cancer cells. 5,7-dihydroxy-3,6,8-trimethoxy-2-phenyl-4H-chromen-4-one (5,7-dihydroxy-3,6,8-trimethoxy flavone) displays activity against more differentiated carcinomas of the colon and pancreas, but minimal cytotoxicity on poorly differentiated carcinomas of these organs. On the contrary, 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H-chromen-4-one (3,5-dihydroxy-6,7,8-trimethoxy flavone) is highly cytotoxic to poorly differentiated carcinomas of the colon, pancreas, and breast with minimal activity against more differentiated carcinomas of the same organs. These differential effects suggest activation of distinct apoptotic pathways. In conclusion, the specific chemical properties of these two flavone isomers dictate mechanistic properties which may be relevant when evaluating biological responses to flavones.

Highlights

There is a group of medicinal plants commonly known in the Andean regions of South America as vira-viras
In this study we present the antineoplastic effects of two known flavone isomers: 5,7-dihydroxy-3,6,8-trimethoxy-2-phenyl-4Hchromen-4-one (5,7-dihydroxy-3,6,8-trimethoxy flavone or flavone A), and 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H-chromen-4-one (3,5-dihydroxy-6,7,8-trimethoxy flavone or flavone B) isolated from Gnaphalium elegans [3] and Achyrocline bogotensis [1] respectively
Flavone A and flavone B are known isomers Flavone A derived from Gnaphalium elegans and previously described by Torrenegra et al, [3] as 5,7 dihydroxy-3,6,8 trimethoxy flavone, and flavone B derived from Achyrocline bogotensis and previously described by Torrenegra et al, [1] as 3,5dihydroxy-6,7,8-trimethoxy flavone, are isomers as shown in figure 1

Summary

Introduction

There is a group of medicinal plants commonly known in the Andean regions of South America as vira-viras. These plants belong to the family Asteraceae, tribe Inuleae, and to the genera Gnaphalium, Achyrocline, and Gamochaeta [1,2,3]. They are annuals or perennials that grow between 2000 and 3200 meters above sea level, to an average height of 1.5 meters.

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Conclusion