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Ngo, Cao, Woo, and Min: Cytotoxic Lactones from the Pericarps of Litsea japonica
Original Article

Natural Product Sciences 2019;25(1):23-27.

Published online: 17 December 2019

DOI: https://doi.org/10.20307/nps.2019.25.1.23

Cytotoxic Lactones from the Pericarps of Litsea japonica

Quynh-Mai Thi Ngo†, , Thao Quyen Cao†, , Mi Hee Woo, Byung Sun Min∗

College of Pharmacy, Drug Research and Development Center, Daegu Catholic University, Gyeongbuk 38430, Republic of Korea

∗Author for correspondence Byung Sun Min, College of Pharmacy, Drug Research and Development Center, Daegu Catholic University, Gyeongbuk 38430, Republic of Korea. Tel: +82-53-850-3613; E-mail: bsmin@cu.ac.kr

† These authors contributed equally to this work

Received 15 May 2018       Revised 10 September 2018       Accepted 17 September 2018

Copyright © 2019 The Korean Society of Pharmacognosy

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

From the pericarps of Litsea japonica (Thunb.) Jussieu, eighteen butanolide derivatives (1–18) were evaluated for their cytotoxic activity against HeLa, HL-60, and MCF-7 cells. Compounds 1–9 with 2-alkylidene-3-hydroxy-4-methylbutanolides structure exhibited cytotoxic activities against cancer-cell lines. Among them, compound 8 (litsenolide D2) exhibited the most potent cytotoxicity against the tested cell lines, including HeLa, HL-60, and MCF-7, with IC50 values of 17.6 ± 1.3, 4.2 ± 0.2, and 12.8 ± 0.0 µM, respectively. Compound 8 induced apoptosis in a dose-dependent manner. Annexin V/Propidium Iodide (PI) double staining confirmed that 8 effectively induced apoptosis in MCF-7 cells. To the best of our knowledge, we have reported cytotoxic activity of butanolides from L. japonica against these cancer-cell lines for the first time.

Keywords: Litsea japonica, Lauraceae, butanolide, lactone, cytotoxic activity, apoptosis

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Fig. 1.
The structures of compounds 1–18 from the pericarps of Litsea japonica.
nps-25-23f1.tif
Fig. 2.
SAR summary of butanonolide derivatives.
nps-25-23f2.tif
Fig. 3.
Flow cytometric analysis of compound 8-induced apoptosis in MCF-7 cell using annexin-V-FLUOS/PI. Cells (1 × 106 cells) were incubated with indicated concentration of 8 for 24 h and stained with annexin-V-FLUOS/PI to analysis apoptosis and necrotic cell populations. Cells in the lower right quadrant represented apoptosis and upper right quadrant. Data are representative of one of three similar experiments.
nps-25-23f3.tif
Table 1.
Cytotoxic activities of compounds 1–18 against Hela, HL-60, and MCF-7 cell lines
Compds IC50, µ Ma
HeLa HL-60 MCF-7
1 47.0 ± 0.2 ± 0.4 38.7 ± 0.3
2 18.4 ± 0.8 5.5 ± 0.6 38.2 ± 0.5
3 45.2 ± 0.9 22.1 ± 1.8 72.2 ± 0.6
4 34.2 ± 0.4 14.0 ± 0.6 24.4 ± 0.7
5 80.3 ± 2.0 26.3 ± 0.0 67.5 ± 0.1
6 100 29.6 ± 0.8 > 100
7 27.7 ± 0.2 11.2 ± 1.5 27.2 ± 0.2
8 17.6 ± 1.3 4.2 ± 0.2 12.8 ± 0.0
9 19.1 ± 1.1 8.1 ± 0.3 22.9 ± 1.1
10 100 23.2 ± 0.5 > 100
11 100 54.9 ± 0.6 > 100
12 54.5 ± 0.3 47.6 ± 0.7 -
13 - 30.2 ± 0.9 > 100
14 100 37.0 ± 1.2 > 100
15 95.4 ± 0.3 28.3 ± 1.6 > 100
16 - - -
17 - 27.4 ± 1.3 > 100
18 - 32.6 ± 0.9 -
Adriamycinb 0.67 ± 0.5 0.24 ± 0.06 53.4 ± 0.2

a The results are presented as mean ± SEM (n = 3).

b Positive control.

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