Traditional Aboriginal Preparation Alters the Chemical Profile of Carica papaya Leaves and Impacts on Cytotoxicity towards Human Squamous Cell Carcinoma

Thao T Nguyen; Marie-Odile Parat; Paul N Shaw; Amitha K Hewavitharana; Mark P Hodson

doi:10.1371/journal.pone.0147956

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Traditional Aboriginal Preparation Alters the Chemical Profile of Carica papaya Leaves and Impacts on Cytotoxicity towards Human Squamous Cell Carcinoma

Thao T Nguyen, Marie-Odile Parat, Paul N Shaw, Amitha K Hewavitharana and Mark P Hodson

PloS one, Vol.11(2), e0147956

2016

DOI: https://doi.org/10.1371/journal.pone.0147956

PMCID: PMC4734615

PMID: 26829042

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Abstract

Plant Leaves - chemistry

Cell Survival - drug effects

Metabolomics

Multivariate Analysis

Plant Extracts - pharmacology

Carcinoma, Squamous Cell - pathology

Humans

Carica - chemistry

Chlorophyll - analogs & derivatives

Keratinocytes - cytology

Reference Standards

Keratinocytes - drug effects

Mass Spectrometry

Cell Line, Tumor

Chromatography, Liquid

Cell Death - drug effects

Chlorophyll - pharmacology

Oceanic Ancestry Group

Carica papaya leaf decoction, an Australian Aboriginal remedy, has been used widely for its healing capabilities against cancer, with numerous anecdotal reports. In this study we investigated its in vitro cytotoxicity on human squamous cell carcinoma cells followed by metabolomic profiling of Carica papaya leaf decoction and leaf juice/brewed leaf juice to determine the effects imparted by the long heating process typical of the Aboriginal remedy preparation. MTT assay results showed that in comparison with the decoction, the leaf juice not only exhibited a stronger cytotoxic effect on SCC25 cancer cells, but also produced a significant cancer-selective effect as shown by tests on non-cancerous human keratinocyte HaCaT cells. Furthermore, evidence from testing brewed leaf juice on these two cell lines suggested that the brewing process markedly reduced the selective effect of Carica papaya leaf on SCC25 cancer cells. To tentatively identify the compounds that contribute to the distinct selective anticancer activity of leaf juice, an untargeted metabolomic approach employing Ultra High Performance Liquid Chromatography-Quadrupole Time of Flight-Mass Spectrometry followed by multivariate data analysis was applied. Some 90 and 104 peaks in positive and negative mode respectively were selected as discriminatory features from the chemical profile of leaf juice and >1500 putative compound IDs were obtained via database searching. Direct comparison of chromatographic and tandem mass spectral data to available reference compounds confirmed one feature as a match with its proposed authentic standard, namely pheophorbide A. However, despite pheophorbide A exhibiting cytotoxic activity on SCC25 cancer cells, it did not prove to be the compound contributing principally to the selective activity of leaf juice. With promising results suggesting stronger and more selective anticancer effects when compared to the Aboriginal remedy, Carica papaya leaf juice warrants further study to explore its activity on other cancer cell lines, as well as investigation to confirm the identity of compounds contributing to its selective effect, particularly those compounds altered by the long heating process applied during the traditional Aboriginal remedy preparation.

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Title: Traditional Aboriginal Preparation Alters the Chemical Profile of Carica papaya Leaves and Impacts on Cytotoxicity towards Human Squamous Cell Carcinoma
Creators: Thao T Nguyen - University of Queensland
Marie-Odile Parat - University of Queensland
Paul N Shaw - University of Queensland
Amitha K Hewavitharana - University of Queensland
Mark P Hodson - University of Queensland
Publication Details: PloS one, Vol.11(2), e0147956
Publisher: United States
Identifiers: 991012894199302368
Academic Unit: Faculty of Science and Engineering; Southern Cross Plant Science; Science
Language: English
Resource Type: Journal article

Traditional Aboriginal Preparation Alters the Chemical Profile of Carica papaya Leaves and Impacts on Cytotoxicity towards Human Squamous Cell Carcinoma

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