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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2023

Open Access 01-12-2023 | Ovarian Cancer | Research

Effects of Leea indica leaf extracts and its phytoconstituents on natural killer cell-mediated cytotoxicity in human ovarian cancer

Authors: Soek-Ying Neo, Yin-Yin Siew, Hui-Chuing Yew, Yaqian He, Keng-Ling Poh, Yi-Chen Tsai, Shu-Ling Ng, Wei-Xun Tan, Teck-Ian Chong, Claire Sophie En-Shen Lim, Samuel Shan-Wei Ho, Deepika Singh, Azhar Ali, Yeh-Ching Linn, Chay-Hoon Tan, See-Voon Seow, Hwee-Ling Koh

Published in: BMC Complementary Medicine and Therapies | Issue 1/2023

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Abstract

Background

The rich biodiversity of medicinal plants and their importance as sources of novel therapeutics and lead compounds warrant further research. Despite advances in debulking surgery and chemotherapy, the risks of recurrence of ovarian cancer and resistance to therapy are significant and the clinical outcomes of ovarian cancer remain poor or even incurable.

Objective

This study aims to investigate the effects of leaf extracts from a medicinal plant Leea indica and its selected phytoconstituents on human ovarian cancer cells and in combination with oxaliplatin and natural killer (NK) cells.

Methods

Fresh, healthy leaves of L. indica were harvested and extracted in 70% methanol by maceration. The crude extract was partitioned with n-hexane, dichloromethane and ethyl acetate. Selected extracts and compounds were analyzed for their effects on cell viability of human ovarian cancer cells, NK cell cytotoxicity, and stress ligands expression for NK cell receptors. They were also evaluated for their effects on TNF-α and IL-1β production by enzyme-linked immunosorbent assay in lipopolysaccharide-stimulated human U937 macrophages.

Results

Leaf extracts of L. indica increased the susceptibility of human ovarian tumor cells to NK cell-mediated cytotoxicity. Treatment of cancer cells with methyl gallate but not gallic acid upregulated the expression of stress ligands. Tumor cells pretreated with combination of methyl gallate and low concentration of oxaliplatin displayed increased levels of stress ligands expression and concomitantly enhanced susceptibility to NK cell-mediated cytolysis. Further, NK cells completely abrogated the growth of methyl gallate-pretreated ovarian cancer cells. The leaf extracts suppressed TNF-α and IL-1β production in human U937 macrophages. Methyl gallate was more potent than gallic acid in down-regulating these cytokine levels.

Conclusions

We demonstrated for the first time that leaf extracts of L. indica and its phytoconstituent methyl gallate enhanced the susceptibility of ovarian tumor cells to NK cell cytolysis. These results suggest that the combined effect of methyl gallate, oxaliplatin and NK cells in ovarian cancer cells warrants further investigation, for example for refractory ovarian cancer. Our work is a step towards better scientific understanding of the traditional anticancer use of L. indica.
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Metadata
Title
Effects of Leea indica leaf extracts and its phytoconstituents on natural killer cell-mediated cytotoxicity in human ovarian cancer
Authors
Soek-Ying Neo
Yin-Yin Siew
Hui-Chuing Yew
Yaqian He
Keng-Ling Poh
Yi-Chen Tsai
Shu-Ling Ng
Wei-Xun Tan
Teck-Ian Chong
Claire Sophie En-Shen Lim
Samuel Shan-Wei Ho
Deepika Singh
Azhar Ali
Yeh-Ching Linn
Chay-Hoon Tan
See-Voon Seow
Hwee-Ling Koh
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2023
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-023-03904-1

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