摘要：ABSTRACT The effect of mahkota dewa polyphenol in the cell proliferation and apoptosis in BaP induced Balb/c rats Background: The polyphenol of mahkota dewa (Phaleria macrocarpa [Scheff.] Boerl) has the potency as antioxidant and anticancer which can handle free radicals, but there has not been extensive research on this. This research is aimed to prove the role of mahkota dewa polyphenol in the cell proliferation inhibition and induct lung carcinogenesis apoptosis in strain Balb/c mice which inducted with benzo(a)pyrene (BaP). Methods: Posttest control group design was carried out among 40 strain Balb/c mice sample, aged 1-2 weeks, weighed 20-30 grams, healthy mice condition. All mice were inducted with BaP and then randomized into 2 groups, as control group and the treatment group. The development of the lung tumor was observed by tissue surgery in the 8th, 17th and 26th week. The data collected were AgNORs, and IHC-TUNEL-apoptosis index dying. The data analysis was conducted using Kruskal-Wallis, Mann-Whitney, One-way ANOVA, and Post hoc test LSD with significance degree of p<α (0.05). Results: The oral administration of mahkota dewa polyphenol showed significantly decreasing cell proliferation, increasing apoptosis index in treatment group in week 8, 17 and 26 (p=0.000). Carcinogenesis incidence for the treatment group week 8 and 26 were 2.32±0.26 and 3.93±0.46, while for the treatment group were 1.88±0.38 and 0.88±0.22 (p=0.000). The cell proliferations for control group week 8 and 26 were 1.57±0.12 and 2.29±0.15, while for the treatment group were 1.53±0.11 and 1.60±0.04 (p=0.000). Apoptosis index for the control group for week 8 was 0.00±0.00 and 0.92±0.22 in week 26, while the treatment group was 1.12±0.71 and 2.02±1.05 (p=0.000). Conclusion: T he administration of mahkota dewa polyphenol effectively inhibited the cell proliferation activity and increased apoptosis measured by apoptosis index. Therefore polyphenol has anticancer and antioxidant activities which can inhibit lung carcinogenesis in Balb/c mice. Keywords: Polyphenol, mahkota dewa (Phaleria macrocarpa [Scheff.] Boerl), apoptosis index, strain Balb/c mice, benzo(a)pyrene (BaP). ABSTRAK Latar belakang: Polifenol mahkota dewa (Phaleria macrocarpa [Scheff.] Boerl) berpotensi sebagai antioksidan dan antikanker yang mampu menangkap radikal bebas, namun belum banyak diteliti. Penelitian ini bertujuan membuktikan peran polifenol mahkota dewa dalam menginhibisi proliferasi sel dan menginduksi apoptosis pada mencit strain Balb/c hasil induksi Benzo(a)pyrene (BaP). Metode: Posttest control group design dengan sampel 40 mencit strain Balb/c, umur 1-2 minggu, berat 20-30 g, kondisi mencit sehat. Semua mencit diinduksi BaP kemudian hewan dirandomisasi menjadi 2 kelompok yaitu kelompok kontrol dan kelompok perlakuan polifenol 50 mg. Perkembangan tumor paru diamati dengan pembedahan jaringan pada minggu ke-8, 17 dan 26. Data dikumpulkan meliputi AgNORs, pengecatan IHC-TUNEL-indeks apoptosis. Analisis data dengan Kruskal-Wallis, Mann-Whitney, One-way ANOVA, post hoc test LSD dengan derajat kemaknaan p<α (0,05). Hasil: Pemberian oral polifenol mahkota dewa sebesar 50 mg secara bermakna memperlihatkan penurunan insidens karsinogenesis paru, proliferasi sel, protein Bax dan peningkatan indeks apoptosis, protein p53, Bcl-2, ekspresi caspase 3, 8, 9 pada kelompok perlakuan pada minggu ke-8, 17 dan 26 (p=0,000). Insidens karsinogenesis untuk kelompok kontrol minggu ke-8, dan 26 sebesar 2,32±0,26 dan 3,93±0,46, sedangkan kelompok perlakuan sebesar 1,88±0,38 dan 0,88±0,22 (p=0,000). Proliferasi sel untuk kelompok kontrol minggu ke-8 dan 26 sebesar 1,57±0,12 dan 2,29±0,15, sedangkan kelompok perlakuan sebesar 1,53±0,11 dan 1,60±0,04 (p=0,000). Indeks apoptosis pada kelompok kontrol minggu ke-8 sebesar 0,00±0,00 dan 0,92±0,22 minggu ke-26, sedangkan kelompok perlakuan sebesar 1,12±0,71 dan 2,02±1,05 (p=0,000). Simpulan: Pemberian polifenol mahkota dewa efektif meng-inhibisi proliferasi sel dan menginduksi apoptosis melalui peningkatan indeks apoptosis. Jadi polifenol mahkota dewa memiliki aktivitas antikanker dan antioksidan mampu menghambat karsinogenesis paru mencit Balb/c.
