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Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and immunomodulatory effects.
J Ethnopharmacol. 2010 Feb 17; 127(3):760-7.JE

Abstract

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 [(3)H]-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-gamma and TNF-alpha 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.

Authors+Show Affiliations

Division of Clinical Immunology, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19961915

Citation

Otsuki, Noriko, et al. "Aqueous Extract of Carica Papaya Leaves Exhibits Anti-tumor Activity and Immunomodulatory Effects." Journal of Ethnopharmacology, vol. 127, no. 3, 2010, pp. 760-7.
Otsuki N, Dang NH, Kumagai E, et al. Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and immunomodulatory effects. J Ethnopharmacol. 2010;127(3):760-7.
Otsuki, N., Dang, N. H., Kumagai, E., Kondo, A., Iwata, S., & Morimoto, C. (2010). Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and immunomodulatory effects. Journal of Ethnopharmacology, 127(3), 760-7. https://doi.org/10.1016/j.jep.2009.11.024
Otsuki N, et al. Aqueous Extract of Carica Papaya Leaves Exhibits Anti-tumor Activity and Immunomodulatory Effects. J Ethnopharmacol. 2010 Feb 17;127(3):760-7. PubMed PMID: 19961915.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and immunomodulatory effects. AU - Otsuki,Noriko, AU - Dang,Nam H, AU - Kumagai,Emi, AU - Kondo,Akira, AU - Iwata,Satoshi, AU - Morimoto,Chikao, Y1 - 2009/12/02/ PY - 2009/08/21/received PY - 2009/11/17/revised PY - 2009/11/24/accepted PY - 2009/12/8/entrez PY - 2009/12/8/pubmed PY - 2010/8/7/medline SP - 760 EP - 7 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 127 IS - 3 N2 - 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 [(3)H]-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-gamma and TNF-alpha 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. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/19961915/Aqueous_extract_of_Carica_papaya_leaves_exhibits_anti_tumor_activity_and_immunomodulatory_effects_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(09)00731-4 DB - PRIME DP - Unbound Medicine ER -