HANDAYANI, 090710158 D (2012) EFEK PEMBERIAN EKSTRAK ETANOL PHYSALIS MINIMA Linn TERHADAP EKSPRESI PROTEIN c-Myc, p53 wild type, Apaf-1, MITOSIS DAN APOPTOSIS SEL KANKER PAYUDARA Penelitian Eksperimental Pada Tikus Wistar. Disertasi thesis, UNIVERSITAS AIRLANGGA.

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Abstract

Physalis minima Linn, widely available in various regions in Indonesia and has been used traditionally as anticancer agent. Ethanol extract of Physalis minima Linn contains some active steroid compound known as physalins, that shows cytotoxic effects on breast cancer cell lines : MCF-7, MDA-MB 231, and several other cancer cells. Ethanol extract of Physalis minima Linn also contains other active compound like flavonoid, poliphenol, clorogenic acid, tanin, vitamin C and glucose etc. Until now there is no accurate data of the ethanol extract of Physalis minima Linn effect on breast cancer in vivo. The aims of this study was to clarify the effect of ethanol extract of Physalis minima Linn on the c-Myc, p53 wild-type, Apaf-1 protein expression, mitosis and apoptosis count on Wistar-rat breast cancer induced N-nitrosomethylurea. An experimental research was performed using female Wistar-rat as animal models. Animal models were divided into 5 groups (n=8). K0 group without induction, while K1, P1, P2, and P3 groups were induced with N-nitrosomethylurea 50 mg/kg body weight, subcutaneous injection at mammary area, once a week for 5 times. At week 15, P1, P2 and P3 groups were administered with ethanol extract of Physalis minima Linn, per oral, 100, 250 and 400 mg/kg body weight, everyday for 4 weeks. At week 20, the termination was done, and breast cancer induced N-nitrosomethylurea was removed for preparations of the slides. The changes in c-Myc, p53 wild-type, Apaf-1 protein expression, mitosis and apoptosis count in all groups were examined and analyzed using multivariate analysis of variance (MANOVA),SPSS 17 for Windows, SPSS Inc. USA (p : 0.05). The result indicates that ethanol extract of Physalis minima Linn has anticancer effect on Wistar-rat breast cancer induced N-nitrosomethylurea (in vivo). Ethanol extract of Physalis minima Linn 100 mg/kg body weight effectively increased p53 wild-type, Apaf-1 protein expression, and apoptosis count, but it is not effective in reducing c-Myc protein expression and mitosis count. The dose of 250 mg/kg body weight of ethanol extract of Physalis minima Linn was effectively lowered c-Myc protein expression and mitosis count; increased p53 wild-type, Apaf-1 expression, and apoptosis count. The dose of 400 mg/kg body weight of ethanol extract of Physalis minima Linn was effectively lowered c-Myc protein expression and mitosis count; increased p53 wild-type, Apaf-1 expression, and apoptosis count, but it was not more effective than 250 mg/kg body weight, in lowering c-Myc protein expression and mitosis count, as well as in increasing Apaf-1 protein expression. Correlation analysis shown there was strong correlation between c-Myc protein expression and mitosis count (r :+0,707; P<0,001), p53 wild type and apoptosis cell count (r :+ 0,858; P<0,001), also Apaf-1 and apoptosis cell count (r :+ 0,922; P<0,001). The conclusions of this study is the ethanol extract of Physalis minima Linn has anticancer effect on Wistar-rat breast cancer induced N-nitrosomethylurea, inhibits cancer cell growth by lowering c-Myc protein expression, increasing the p53 wild type and Apaf-1 protein expression, lowering mitosis count and increasing apoptosis count. Apoptotic induction is more dominan than mitosis inhibition.

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