Main Article Content
Abstract
Background: Carcinogenic compound can cause cancer, one of which is 7,12- Dimethylbenz anthrasen (DMBA). Therapy used is chemotherapy using doxorubicin. However, doxorubicin can cause side effects and not specific enough, so it can also impair normal cells and cause resistance, so Long jack roots are needed as co- chemotherapy agent.
Objective: To assess the effect of giving co-chemotherapy ethyl acetate fraction of Long jack roots and doxorubicin on the development of breast cancer through inhibition interleukin-6 expression.
Methods: A total of 35 female rats SD strain were divided into 5 intervention group, each group contained 7 rats, namely Group 1 (baseline given feed and water), Group 2 (DMBA 20 mg / kg given 2x a week for 5 weeks), Group 3 (DMBA 20mg / kg + Long jack roots Ethyl acetate fraction 100 mg / kg), Group 4 (DMBA 20 mg / kg + Doxorubicin 1,17mg / kg), Group 5 (DMBA 20 mg / kg + Long jack roots ethyl acetate fraction 100 mg / kg + Doxorubicin 1,17mg / kg), then on the 16th week, surgery was done to remove animal’s mammae and organs and to conduct immunohistochemistry test with anti interleukin-6.
Results: Interleukin-6 expression test result% with the average value of group I, II, III, IV and V respectively, 6.56 ± 3.50%; 47.21 ± 9.48%; 20.83 ± 10.40%; 49.39 ± 9.87% and 58.37 ± 17.32%.
Conclusion: The administration of co-chemotherapy ethyl acetate fraction of longjack roots (Eurycoma longifolia Jack) and doxorubicin is effective in
lowering aromatase expression, however not effective in reducing IL-6 expression compared to single regiment doxorubicin in DMBA-induced rat models.
Keywords
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References
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- Smith L, Watson MB, Kane SLO, Drew PJ, Lind MJ, Cawkwell L. The analysis of doxorubicin resistance in human breast cancer cells using antibody microarrays. Molecular Cancer Therapeutics. 2006;5(August):2115–21.
- Wang LM, Chi YJ, Wang LN, Nie L, Zou YH, Zhao TN, et al. Expression of interleukin-6 in rat model of doxorubicin-induced nephropathy. Chinese Journal of Contemporary Pediatrics. 2010;12(11):912–4.
- Jenie RI, Meiyanto E. Aplikasi ko-kemoterapi fraksi daun sambung nyawa pada sel kanker payudara MCF-7. Majalah Ilmu Kefarmasian. 2009;VI(3):132–41.
- Tyagi AK, Agarwal C, Chan DC, Agarwal R. Synergistic anti-cancer effects of silibinin with conventional cytotoxic agents doxorubicin, cisplatin and carboplatin against human breast carcinoma MCF-7 and MDA-MB468 cells. Oncology Reports. 2004;11(2):493–9.
- Sharma G, Tyagi AK, Singh RP, Chan DC, Agarwal R. Synergistic anti-cancer effects of grape seed extract and conventional cytotoxic agent doxorubicin against human breast carcinoma cells. Breast Cancer Research and Treatment. 2004;85(1):1–12.
- Nurani LH. Kajian aktivitas antioksidan dan imunomodulator agen kemopreventif sediaan terstandar isolat aktif kuasinoid ekstrak akar pasak bumi (Eurycoma longifolia Jack) pada kanker payudara tikus putih yang diinduksi DMBA. Yogyakarta; 2010.
- Nurani LH, Widyarini S, Mursyidi A, Puspitawati F, Nugraheni SN, Nurliawati Y. Efek pemberian kombinasi fraksi etil asetat ekstrak etanol akar pasak bumi (Eurycoma longifolia Jack) dan doxorubicin terhadap gambaran histopatologik payudara, pankreas, paru, jantung dan otak pada tikus galur Sprague Dawley yang diinduksi 7.12-dimetilb. Yogyakarta; 2015.
- Niah R. Efek kombinasi fraksi etil asetat ekstrak etanol 70% akar pasak bumi (Eurycoma longifolia Jack) dengan doxorubicin terhadap apoptosis, antiproliferasi dan ekspresi RAS pada sel T47D. Universitas Ahmad Dahlan; 2015.
- Hurd C, Khattree N, Alban P, Nag K, Jhanwar SC, Dinda S, et al. Hormonal regulation of the p53 tumor suppressor protein in T47D human breast carcinoma cell line. Journal of Biological Chemistry. 1995;270(48):28507–10.
- King RJB. Cancer Biology. 2nd ed. London: Pearson Education Limited; 2000.
- Meiyanto E. Prosedur tetap pengamatan ekspresi protein dengan metode imunohistokimia. Yogyakarta; 2009.
- Wijayanti NR. Pengaruh krim ekstrak etanol akar pasak bumi (Eurycoma longifolia Jack) terhadap ekspresi IL-6 pada mencit Balb/c yang dipapar sinar UV-C. Universitas Ahmad Dahlan; 2013.
- Arifah AN, Nurkhasanah. Efek fraksi etil asetat ekstrak etanol akar pasak bumi (Eurycoma longifolia Jack) terhadap aktivitas fagositosis makrofag secara in vitro. Pharmaçiana. 2014;4(1):9–14.
- Leu C, Wong F, Chang C, Huang S, Hu C. Interleukin-6 acts as an antiapoptotic factor in human esophageal carcinoma cells through the activation of both STAT3 and mitogen- activated protein kinase pathways. Oncogene. 2003;22(49):7809–18.
- Hodge DR, Hurt EM, Farrar WL. The role of IL-6 and STAT3 in inflammation and cancer. European Journal Cancer 2005;41(16):2502–12.
- Meiyanto E, Tasminatun S, Susilowati S, Murwanti R, Sugiyanto. Penghambatan karsinogenesis kanker payudara tikus terinduksi DMBA pada fase post inisiasi oleh ekstrak etanolik daun Gynura procumbens (Lour). Majalah Farmasi Indonesia. 2007;18(4):169–75.
- Hakkak R, Holley AW, Macleod SL, Simpson PM, Fuchs GJ, Jo CH, et al. Obesity promotes 7,12-dimethylbenz(a)anthracene-induced mammary tumor development in female zucker rats. Breast Cancer Research. 2005;7(5):627–33.
- Hilakivi-clarke L. Estrogens, BRCA1, and breast cancer. Cancer Research. 2000; 60(18):4993–5001.
- Brunton LL, Lazo JS, Keith. Goodman and Gilman’s The pharmacological basis of therapeutics. 11th ed. McGraw-Hill; 2005.
- Sullivan NJ. Breast cancer: Focusing tumor microenvironment, stem cells and metastasis. In: Interleukin-6 in the breast tumor microenvironment. 2nd ed. In Tech; 2011. p. 165–182.
- Kim M, Oskarsson T, Acharyya S, Nguyen DX, Zhang XH, Norton L, et al. Tumor self-seeding by circulating cancer cells. Cell. 2009;139(7):1315–26.
- Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: A leading role for STAT3. Nature Reviews Cancer. 2009;9(11):798–809.
- Gewirtz DA. A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochemistry Pharmacology. 1999;57(7):727–41.
- Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines?: Molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacological Reviews. 2004;56(2):185–229.
References
Singletary KW, Matthew JS, Monica G, Richard BVB, Matthew W, Agnes R. Inhibition of rat mammary tumorigenesis by concord grape juice constituents. Journal of Agricultural and Food Chemistry. 2003;51(25):7280–6.
Smith L, Watson MB, Kane SLO, Drew PJ, Lind MJ, Cawkwell L. The analysis of doxorubicin resistance in human breast cancer cells using antibody microarrays. Molecular Cancer Therapeutics. 2006;5(August):2115–21.
Wang LM, Chi YJ, Wang LN, Nie L, Zou YH, Zhao TN, et al. Expression of interleukin-6 in rat model of doxorubicin-induced nephropathy. Chinese Journal of Contemporary Pediatrics. 2010;12(11):912–4.
Jenie RI, Meiyanto E. Aplikasi ko-kemoterapi fraksi daun sambung nyawa pada sel kanker payudara MCF-7. Majalah Ilmu Kefarmasian. 2009;VI(3):132–41.
Tyagi AK, Agarwal C, Chan DC, Agarwal R. Synergistic anti-cancer effects of silibinin with conventional cytotoxic agents doxorubicin, cisplatin and carboplatin against human breast carcinoma MCF-7 and MDA-MB468 cells. Oncology Reports. 2004;11(2):493–9.
Sharma G, Tyagi AK, Singh RP, Chan DC, Agarwal R. Synergistic anti-cancer effects of grape seed extract and conventional cytotoxic agent doxorubicin against human breast carcinoma cells. Breast Cancer Research and Treatment. 2004;85(1):1–12.
Nurani LH. Kajian aktivitas antioksidan dan imunomodulator agen kemopreventif sediaan terstandar isolat aktif kuasinoid ekstrak akar pasak bumi (Eurycoma longifolia Jack) pada kanker payudara tikus putih yang diinduksi DMBA. Yogyakarta; 2010.
Nurani LH, Widyarini S, Mursyidi A, Puspitawati F, Nugraheni SN, Nurliawati Y. Efek pemberian kombinasi fraksi etil asetat ekstrak etanol akar pasak bumi (Eurycoma longifolia Jack) dan doxorubicin terhadap gambaran histopatologik payudara, pankreas, paru, jantung dan otak pada tikus galur Sprague Dawley yang diinduksi 7.12-dimetilb. Yogyakarta; 2015.
Niah R. Efek kombinasi fraksi etil asetat ekstrak etanol 70% akar pasak bumi (Eurycoma longifolia Jack) dengan doxorubicin terhadap apoptosis, antiproliferasi dan ekspresi RAS pada sel T47D. Universitas Ahmad Dahlan; 2015.
Hurd C, Khattree N, Alban P, Nag K, Jhanwar SC, Dinda S, et al. Hormonal regulation of the p53 tumor suppressor protein in T47D human breast carcinoma cell line. Journal of Biological Chemistry. 1995;270(48):28507–10.
King RJB. Cancer Biology. 2nd ed. London: Pearson Education Limited; 2000.
Meiyanto E. Prosedur tetap pengamatan ekspresi protein dengan metode imunohistokimia. Yogyakarta; 2009.
Wijayanti NR. Pengaruh krim ekstrak etanol akar pasak bumi (Eurycoma longifolia Jack) terhadap ekspresi IL-6 pada mencit Balb/c yang dipapar sinar UV-C. Universitas Ahmad Dahlan; 2013.
Arifah AN, Nurkhasanah. Efek fraksi etil asetat ekstrak etanol akar pasak bumi (Eurycoma longifolia Jack) terhadap aktivitas fagositosis makrofag secara in vitro. Pharmaçiana. 2014;4(1):9–14.
Leu C, Wong F, Chang C, Huang S, Hu C. Interleukin-6 acts as an antiapoptotic factor in human esophageal carcinoma cells through the activation of both STAT3 and mitogen- activated protein kinase pathways. Oncogene. 2003;22(49):7809–18.
Hodge DR, Hurt EM, Farrar WL. The role of IL-6 and STAT3 in inflammation and cancer. European Journal Cancer 2005;41(16):2502–12.
Meiyanto E, Tasminatun S, Susilowati S, Murwanti R, Sugiyanto. Penghambatan karsinogenesis kanker payudara tikus terinduksi DMBA pada fase post inisiasi oleh ekstrak etanolik daun Gynura procumbens (Lour). Majalah Farmasi Indonesia. 2007;18(4):169–75.
Hakkak R, Holley AW, Macleod SL, Simpson PM, Fuchs GJ, Jo CH, et al. Obesity promotes 7,12-dimethylbenz(a)anthracene-induced mammary tumor development in female zucker rats. Breast Cancer Research. 2005;7(5):627–33.
Hilakivi-clarke L. Estrogens, BRCA1, and breast cancer. Cancer Research. 2000; 60(18):4993–5001.
Brunton LL, Lazo JS, Keith. Goodman and Gilman’s The pharmacological basis of therapeutics. 11th ed. McGraw-Hill; 2005.
Sullivan NJ. Breast cancer: Focusing tumor microenvironment, stem cells and metastasis. In: Interleukin-6 in the breast tumor microenvironment. 2nd ed. In Tech; 2011. p. 165–182.
Kim M, Oskarsson T, Acharyya S, Nguyen DX, Zhang XH, Norton L, et al. Tumor self-seeding by circulating cancer cells. Cell. 2009;139(7):1315–26.
Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: A leading role for STAT3. Nature Reviews Cancer. 2009;9(11):798–809.
Gewirtz DA. A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochemistry Pharmacology. 1999;57(7):727–41.
Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines?: Molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacological Reviews. 2004;56(2):185–229.