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

Abstract

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.

Medicinal Plants Used in Traditional Management of Cancer in Uganda: A Review of Ethnobotanical Surveys, Phytochemistry, and Anticancer Studies

“…In peripheral blood mononuclear cells, the extract reduced the production of IL-2 and IL-4 whereas it increased the production of 1 types cytokines such as IL-12p40, IL-12p70, INF-c, and TNF-∝ . e expression of 23 immunomodulatory genes was enhanced by the addition of papaya extract [114] Leaf juice not only exhibited a stronger cytotoxic effect on human squamous cell carcinoma (SCC25 cancer) cells but also produced a significant cancer-selective effect as shown by tests on noncancerous human keratinocyte HaCaT cells [115] Catharanthus roseus (L.) G. Don.…”

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“…[99] Chlorophyll found in green Carica papaya leaves shows cytotoxicity toward human squamous cell carcinoma. [100] Green plant extracts stop adhesion, invasion, and migration in SK-Hep1 human hepatoma cancer cells. [101] Photodynamic therapy shows synergistic effect with doxorubicin on multiple drug-resistant uterine sarcoma cell MES-SA/Dx5.…”

Ftir Spectroscopic Analysis of Ethanolic and N-Hexane Extracts of Male and Female Tree Leaves of Carica Papaya Linn

“…Traditionally, various extracts of Carica papaya Linn tree leaves are consumed in various ailments including dengue hemorrhagic fever 1,5 . Leaves of Carica papaya L. exhibit beneficial effects and in Asia leaves of the plant are widely used as medicine [6][7][8][9] Phytoconstituents of leaves shows hepatoprotective, hypoglycemic, anti-fertility, immunomodulatory, wound healing as well as antiviral properties [10][11][12] .…”