Malaysian Applied Biology Journal

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29-1&2-16

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Malays. Appl. Biol. (December 2000) 29(1&2): 121-126

INCREASED LEVELS OF APOPTOSIS CORRELATE WITH p53 PROTEIN ACCUMULATION IN RESPONSE TO STYRYLPYRONE DERIVATIVE (SPD) TREATMENT OF THE "HUGGINS TUMOR"

MEENAKSHII, N., LEE, A., AZIMAHTOL, H.L.P. and HASIDAH, S.

School of Biosciences & Biotechnology, Faculty of Science & Technology Universiti Kebangsaan Malaysia 43600 Bangi, Selangor, Malaysia

ABSTRACT

Styrylpyrone derivative (SPD), an active pharmacological compound purified from a local plant has been extensively studied in regard to its anticancer activity in both in vitro and in vivo models. The following experimentation is an endeavour to profile/map the mechanism of action of this chemopreventive agent with emphasis on tumor suppressor function - p53 protein and elicitation of apoptosis. Sprague-Dawley rats bearing the "Huggins tumor" were subjected to a 10 mg/kg BW of Styrylpyrone derivative(SPD) dissolved in the excipient, Nigella saliva oil. for a treatment period of 12 weeks. Tumors excised at the end of the 12 week treatment period were paraffin embedded and sectioned for apoptosis detection employing the TUNEL assay. p53 status of mammary tumor samples was determined by electrophoresing crude protein extracts of tumors on SDS-PAGE; western blotting, probing with anti-wild type p53 clone PAb 122 and finally detection. An increased level of apoptosis was observed in all tumors from SPD-treated rats in comparison with the controls. Likewise, wild type p53 protein accumulation was more profound in tumor samples from SPD treated rats. These results imply that SPD might have triggered an increased tumor suppressor function on the part of p53 protein accumulation which then elicits augmented levels of apoptosis. Hence, SPD is capable oi tumoricidal and tumoristatic effects, possibly through a p53-dependent apoptotic mechanism.


ABSTRAK

Terbitan stirilpiron (SPD), sebatian farmakologi aktif yang dipencilkan daripada suatu tumbuhan tempatan banyak dikaji akan aktiviti antikansernya pada kedua-dua model in vitro dan in vivo. Eksperimen ini merupakan suatu usaha untuk mencirikan mekanisme tindakan agen kemopreventif ini dengan penumpuan pada fungsi penindasan tumor-protein p53 dan pencetusan apoptosis. Tikus-tikus Sprague-Dawley yang bertumor "Huggin" diberikan perlakuan 10 mg/kg BT SPD yang dilarutkan dalam eksipien - minyak Nigella saliva untuk tempoh 12 minggu. Tumor yang dieksisikan pada penghujung minggu 12 dibenamkan dengan parafin, dihiris dan dikesan untuk apoptosis menggunakan asai TUNEL. Status p53 sampel tumor mamari ditentukan dengan mengelektroforesiskan ekstrak kasar protein pada SDS-PAGE, pendapan western; pengeraman dengan antibodi anti-p53 liar, PAb 122 dan pengesanan. Peningkatan aras apoptosis yang lebih nyata dicerap pada sampel tumor tikus perlakuan SPD berbanding kawalan. Begitu juga, penggumpulan protein p53 jenis liar lebih ketara pada sampel tumor tikus perlakuan SPD. Kajian ini mendapati SPD mungkin mencetuskan peningkatan fungsi penindasan tumor dengan penggumpulan protein p53 yang seterusnya meningkatkan aras apoptosis. Maka, kesar tumorisidal dan tumoristatik SPD mungkin disebabkan oleh mekanisme apoptosis bersandar-p53.

Key words: Styrylpyrone derivative, "Huggins tumor", p53 protein, apoptosis.

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