6-C-Methyl Flavonoids Isolated from Pinus densata Inhibit the
                    Proliferation and Promote the Apoptosis of the HL-60 Human Promyelocytic
                    Leukaemia Cell Line

Rongcai Yue; Bo Li; Yunheng Shen; Huawu Zeng; Bo Li; Hu Yuan; Yiren He; Lei Shan; Weidong Zhang

doi:10.1055/s-0033-1350617

Planta Medica, Table of Contents

Planta Med 2013; 79(12): 1024-1030
DOI: 10.1055/s-0033-1350617

Biological and Pharmacological Activity

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

6-C-Methyl Flavonoids Isolated from Pinus densata Inhibit the Proliferation and Promote the Apoptosis of the HL-60 Human Promyelocytic Leukaemia Cell Line

Rongcai Yue

¹School of Pharmacy, Second Military Medical University, Shanghai, China

,

Bo Li

¹School of Pharmacy, Second Military Medical University, Shanghai, China

,

Yunheng Shen

¹School of Pharmacy, Second Military Medical University, Shanghai, China

,

Huawu Zeng

¹School of Pharmacy, Second Military Medical University, Shanghai, China

,

Bo Li

¹School of Pharmacy, Second Military Medical University, Shanghai, China

,

Hu Yuan

²School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China

,

Yiren He

¹School of Pharmacy, Second Military Medical University, Shanghai, China

,

Lei Shan

¹School of Pharmacy, Second Military Medical University, Shanghai, China

,

Weidong Zhang

¹School of Pharmacy, Second Military Medical University, Shanghai, China

²School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China

› Author Affiliations

Abstract

Three structurally related 6-C-methyl flavonoids isolated from Pinus densata, including 5,4′-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone (PD1), 5,7,4′-trihydroxy-3,8-dimethoxy-6-C-methylflavone (PD2), and 5,7,4′-trihydroxy-3-methoxy-6-C-methylflavone (PD3), were tested for their ability to inhibit the proliferation and promote the apoptosis of the HL-60 human leukaemia cell line. Cytotoxicity assays in the HL-60 human cancer cell line demonstrated that 5,4′-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone exhibited the most potent cytotoxicity of the three structurally related 6-C-methyl flavonoids. 5,4′-Dihydroxy-3,7,8-trimethoxy-6-C-methylflavone inhibited the proliferation of HL-60 cells in a dose-dependent manner with an IC₅₀ of 7.91 µM (48 h treatment). Furthermore, 5,4′-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone-induced apoptosis was associated with mitochondrial membrane disruption and cytochome c release. Flow cytometry analyses revealed an increase in the hypodiploid population in 5,4′-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone-treated HL-60 cells. Treatment with a concentration of 5,4′-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone that induced apoptosis activated caspase-3 but did not activate caspase-1. A caspase-3 inhibitor (Ac-DEVD-CHO), but not a caspase-1 inhibitor (Ac-YVAD-CHO), reversed the cytotoxic effects of 5,4′-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone in HL-60 cells. These data demonstrated that 5,4′-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone effectively induced the apoptosis of HL-60 cells and exhibited significant anticancer activity via the mitochondrial caspase-3-dependent apoptosis pathway.

Key words

Pinus densata - Pinaceae - apoptosis - HL-60 - caspase-3 - 6-C-methyl flavonoids

Full Text

References

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