Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and immunomodulatory effects

Journal of Ethnopharmacology 127 (2010) 760–767

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Journal of Ethnopharmacology

journal homepage: www.elsevier.com/locate/jethpharm

Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and

immunomodulatory effects

Noriko Otsukia,1, Nam H. Dangb,1, Emi Kumagaia, Akira Kondoc, Satoshi Iwataa, Chikao Morimotoa,d,∗

a Division of Clinical Immunology, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Japan

b Division of Hematology/Oncology, The University of Florida, Gainesville, FL, USA

c Kondo Hospital, 1-6-25, Nishishinhama, Tokushima, Tokushima 770-8008, Japan

d Department of Rheumatology and Allergy, Research Hospital, The Institute of Medical Science, The University of Tokyo, Japan

a b s t r a c t

Aim of the study: Various parts of Carica papaya Linn. (CP) have been traditionally used as ethnomedicine

for a number of disorders, including cancer. There have been anecdotes of patients with advanced cancers

achieving remission following consumption of tea extract made from CP leaves. However, the precise

cellular mechanism of action of CP tea extracts remains unclear. The aim of the present study is to

examine the effect of aqueous-extracted CP leaf fraction on the growth of various tumor cell lines and

on the anti-tumor effect of human lymphocytes. In addition, we attempted to identify the functional

molecular weight fraction in the CP leaf extract.

Materials and methods: The effect of CP extract on the proliferative responses of tumor cell lines and

human peripheral blood mononuclear cells (PBMC), and cytotoxic activities of PBMC were assessed by

[3H]-thymidine incorporation. Flow cytometric analysis and measurement of caspase-3/7 activities were

performed to confirm the induction of apoptosis on tumor cells. Cytokine productions by PBMC were

measured by ELISA. Gene profiling of the effect of CP extract treatment was performed by microarray

analysis and real-time RT-PCR.

Results: We observed significant growth inhibitory activity of the CP extract on tumor cell lines. In PBMC,

the production of IL-2 and IL-4 was reduced following the addition of CP extract, whereas that of IL-

12p40, IL-12p70, IFN-_ and TNF-_ was enhanced without growth inhibition. In addition, cytotoxicity of

activated PBMC against K562 was enhanced by the addition of CP extract. Moreover, microarray analyses

showed that the expression of 23 immunomodulatory genes, classified by gene ontology analysis, was

enhanced by the addition of CP extract. In this regard, CCL2, CCL7, CCL8 and SERPINB2 were representative

of these upregulated genes, and thus may serve as index markers of the immunomodulatory effects of

CP extract. Finally, we identified the active components of CP extract, which inhibits tumor cell growth

and stimulates anti-tumor effects, to be the fraction with M.W. less than 1000.

Conclusion: Since Carica papaya leaf extract can mediate a Th1 type shift in human immune system,

our results suggest that the CP leaf extract may potentially provide the means for the treatment and

prevention of selected human diseases such as cancer, various allergic disorders, and may also serve as

immunoadjuvant for vaccine therapy.

© 2009 Elsevier Ireland Ltd. All rights reserved.


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