Effect of protein fraction of Carica papaya L. leaves on the expressions of p53 and Bcl-2 in breast cancer cells line

Rumiyati ., Sismindari ., Ariyani .


Carica papaya L. leave was known containing Ribosome-inactivating proteins (RIPs), which demonstrated to have an in vitro cytotoxic effect on cancer cell lines. This researh examined the effect of protein fraction containing RIPs isolated from Carica papaya L. on the expressions of p53 and Bcl-2, regulator proteins on apoptosis process, in breast cancer cell lines (T47D).

RIPs from Carica papaya L. leaves were isolated by amonium sulfat precipitation. This fraction was analyzed by the activity of cleaving supercoiled double stranded DNA, in order to identify the presence of RIP. The active fraction was then tested of the citotoxic activity on breast cancer cell lines followed by analysing the expressions of p53 and bcl2 using immunohistochemistry technique.

The results indicated that the protein fraction possessed cytotoxic activity in breast cancer cell line with the IC50 of 2.8 mg/mL. The expression level of p53 was increased by 59.4%, while Bcl-2 protein was \ decreased by 63%. These results suggested that this protein could induce apoptotic process.

Key words : protein fraction, Carica papaya L. , expression of p53 and Bcl-2

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Barbieri, L., and Batteli, M.G., 1993, Ribosome - inactivating protein From Plants, Biochem et Biophys, Acta,1164,237-282.

Burlacu, A., 2003, Regulation of Apoptosis by Bcl-2 amily proteins (Review), J. Cell. Mol. Med., Vol.7, No. 3, 249-257.

Bagga, S., Seth, D. and Batra , J.K., 2002, The Cytotoxic Activity of Ribosome-inactivating Protein Saporin-6 Is Attributed to Its rRNA N-Glycosidase and Internucleosomal DNA Fragmentation Activities, J. Biol. Chem., Vol. 278, Issue 7, 4813-4820.

Eperon, I., 1989, Biochemistry Department Univ. of Leicester UK (Personal communication).

Goldmacher, Y.S., Bourret, L.A., Levine, B.A., Rasmussen, R.A., Pourshadi, M., Lambert, J.M., and Andeson, K.C., 1994, Anti-CD38-blocked ricin : An Immunotoxin For The Treatment Of Multiple Myeloma, Blood 84, 3017 - 3025.

Hanif, R., Qiao, L., Shiff, S.J., and Rigas, B., 1997, Curcumin, a Natural Plant phenolic Food Additive, Inhibits Cell Proliferation and Induce Cell Cycle Changes in Colon Adenocarcinoma Cell Lines by a Prostaglandin-independent Pathway, J. Lab. Clin. Med., 577-579.

Ikawati Z., Sudjadi, Widyaningsih E, Puspitasari D and Sismindari, 2003, Induction of apoptosis by protein fraction isolated from the leaves of M. jalapa L on HeLa and Raji cell-lines, Opem 3, 151-156.

Ikawati, Z., Sudjadi and Sismindari, 2006, Cytotoxic against tumor cell lines of a Ribosomeinactivating like protein isolated from leaves of Mirabilis jalapa L , Malaysian J. Pharm. Sciences, 4 (1) in press.

Ling, J., Lia, and W. Wang , T.P., 1994, Cleavage of Supercoiled Double Stranded DNA by Several Ribosom - inactivating protein in Vitro, FEBS Letters, 143-146.

Kuwana, T., and Newmeyer, D.D., 2003, Bcl-2-family proteins and role of mitochondria in apoptosis, Current Opinion in Cell Biology, Elsevier,15:1-9.

Miller, L.D., Smeds, Johanna, George, Joshy, and Vega, VB., 2005, Genetics, PNAS, 102 (38) : 13550-13555.

Narayanan, S., Surendranathb, K., Borap, N., and Suroliaa, A., 2005, Ribosome Inactivating Proteins and Apoptosis, FEBS Letters, 579 (6 ) : 1324-1331.

Purnamawati, D., 1997, Identifikasi Ribosome-inactivating protein dari Tanaman Carica papaya L. dengan Metode Pemotongan DNA Superkoil, Skripsi, Fakultas Farmasi, Universitas Gadjah Mada, Yogyakarta.

Rumiyati, Sismindari and Sudjadi, 2000, Aktivitas N-glikosidase Fraksi Protein Aktif daun Carica papaya L. pada rRNA yeast, Majalah Farmasi Indonesia 11(1), 25 – 30.

Rumiyati, Sismindari and Sudjadi, 2003, Uji Sitotoksisitas Fraksi Protein Daun Carica papaya L. Pada sel HeLa, Majalah Farmasi Indonesia, (14)1, 270 – 275.

Sismindari, Husaana A. and Mubarika S., 1998, In-vitro cleavage of supercoiled double stranded DNA by crude extract of Annona squamosa L. Indon J Pharm 9, 146-152.

Sismindari and Lord, J.M., 2000, RNA-N-glicosidase Activity of Leaves Crude Extract from Carica papaya L., Morinda citrofolia L., Mirabilis jalapa L., J. Biotechnology; Spesial Issue, 342-345

Xu, Z.W., Friess, H., Buchler, M.W., and Solioz, M., 2001,Overexpression of Bax sensitizes human pancreatic cancer cells to apoptosis induced by chemotherapeutic agents, Cancer Chemother. Pharmacol, 49 : 504 - 510.

Vita, V.T., Hellman, S., and Roenberg, S.A., 2001, Cancer Principles and Practise of Oncology 6 th , 1633-1647, Lippincott Williams & Wilkins, USA.

DOI: http://dx.doi.org/10.14499/indonesianjpharm0iss0pp170-176


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