Terfenadine Meningkatkan Aktifitas Caspase-9 pada Kultur Sel Melanoma Maligna

Sjafrida Sjafrida, Elfina G Sadono


Pencarian agen anti kanker baru pada melanoma maligna yang lebih selektif merupakan prioritas utama. Penelitian ini bertujuan mengetahui pengaruh pemberian terfenadine terhadap aktifitas caspase-9 pada kultur melanoma maligna cell line CRL 1872 dan hubungan antara perubahan dosis terfenadin dengan perubahan aktivitas caspase-9. Penelitian ini merupakan analitik eksperimental pada kultur melanoma maligna cell line CRL 1872 yang dipapar dengan terfenadine. Kultur cell line melanoma maligna dibagi menjadi 6 kelompok yaitu kelompok kontrol, kultur+5 μM terfenadine, kultur+10 μM terfenadine, kultur+25 μM terfenadine, kultur+40 μM terfenadine. Spesimen diinkubasi selama 8 jam lalu dilakukan pengecatan imunohistokimia menggunakan antibodi caspase-9. Aktivitas caspase-9 diamati dengan mikroskop okular dengan pembesaran 1000x, sel-sel aktivitas  caspase-9 ditunjukkan dengan warna coklat pada inti sel dengan counter stain warna biru. Data hasil pengamatan dilakukan analisa statistik dengan uji ANOVA, uji Tukey, uji korelasi dan regresi. Terdapat perbedaan efek terfenadine pada setiap perlakuan terhadap aktivitas caspase-9 pada kultur melanoma maligna cell line CRL 1872 (p<0,001). Korelasi pemberian terfenadine dengan aktivitas caspase-9 pada kultur melanoma maligna cell line CRL 1872 (r=0,844; p=0,000) mempunyai korelasi positif yang signifikan. Pemberian terfenadine berpengaruh dalam meningkatkan aktifitas caspase-9 pada kultur melanoma maligna cell line CRL 1872.
Kata Kunci: Apoptosis, caspase-9, melanoma maligna, terfenadine


Wolff K and Goldsmith LA. Fitzpatrick's Dermatology in General Medicine. 7th edition. USA: The McGraw-Hill Companies; 2008; p. 1134-1157.

Andrew S. Disease of the Skin: Clinical Dermatology. Canada: Saunders Elsevier; 2006; p. 694-699.

Rigel DS and Carucci JA. Malignant Melanoma: Prevention, Early Detection and Treatment in the 21st Century. A Cancer Journal for Clinicians. 2000; 50(4): 215-236.

Markovic SN, Erickson LA, Rao R, et al. Malignant Melanoma in the 21st Century, Part 2: Staging, Prognosis, and Treatment. Mayo Clinic Proceedings. 2007; 82(4): 490-513.

Khurana AK. Comprehensive Ophthalmology. 4th edition. New Delhi: New Age International; 2007; p. 162-166.

Hurst E, Harbour W, and Cornelius LA. Ocular Melanoma. A Review and the Relationship to Cutaneous Melanoma. Archives of Dermatology. 2003; 139: 1067-1073.

Halama N, Zoernig I, and Jaeger D. Review Article. Advanced Malignant Melanoma: Immunologic and Multimodal Therapeutic Strategies. Journal of Oncology. 2010; 2010: 8.

Hsan KM, Chen CC, and Shyur LF. Current Research and Development of Chemotherapeutic Agents for Melanoma. Cancers Journal. 2010; 2: 397-419.

Jangi SM, Dı´az-Pe´rez J, Ochoa-Lizarralde B, et al. H1 Histamine Receptor Antagonists Induce Genotoxic and Caspase-2-dependent Apoptosis in Human Melanoma Cells. Carcinogenesis. 2006; 27(9): 1787–1796.

Yin XM and Dong Z. Essentials of Apoptosis: A Guide for Basic and Clinical Research. New Jersey: Humana Press; 2003.

Elkon KB. Apoptosis and Its Relevance to Autoimmunity. Current Directions in Autoimmunity. 2006; 9: 1-17.

Jangi SM, Asumendi A, Arlucea J, et al. Apoptosis of Human T-cell Acute Lymphoblastic Leukemia Cells by Diphenhydramine, an H1 Histamine Receptor Antagonist. Oncology Research. 2004; 14(7-8): 363-372.

Haak FM, Darvas Z, Hegyesi Y, et al. Histidine Decarboxylase Expression in Human Melanoma. The Journal of Investigative Dermatology. 2000; 115: 345-352.

Hegyesi H, Somlai B, and Varga VL. Suppression of Melanoma Cell Proliferation by Histidine Decarboxylase Specific Antisense Oligonucleotides. The Journal of Investigative Dermatology. 2001; 117: 151-153.

Graff L, Frungieri M, Zanner R, et al. Short Communication. Expression of Histidine Decarboxylase and Synthesis of Histamine by Human Small Cell Lung Carcinoma. American Journal of Pathology. 2002; 160: 1561-1565.

Pos Z, Safrany G, Muller K, et al. Phenotypic Profiling of Engineered Mouse Melanomas with Manipulated Histamine Production Identifies Histamine H2 Receptor and Rho-c as Histamine Regulated Melanoma Progression Marker. Cancer Research. 2005; 65: 4458-4466.

Rizzuto R, Pinton P, and Ferrari D. Calcium and Apoptosis: Facts and Hypotheses. Oncogene. 2003; 22: 8619 - 8627.

Henry-Mowatt J, Dive C, and Martinou JC. Role of Mitochondrial Membrane Permiabilization in Apoptosis and Cancer. Oncogene. 2004; 23: 2850-2860.

Cerella C, Diederich M, and Ghibelli L. Review Article: The Dual Role of Calcium as Messenger and Stressor in Cell Damage, Death, and Survival. International Journal of Cell Biology. 2009; 2010: 14.

Wang X. The Expanding Role of Mitochondria in Apoptosis. Genes and Development. 2001; 15: 2922-2933.

Van Loo G, Saelens X, and Van Gurp M. The Role of Mitochondrial Factors in Apoptosis: A Russian Roulette with More Than One Bullet. Cell Death and Differentiation. 2002; 9: 1031-1042.

Limb SL and Wood RA. Antihistamine. USA: The McGraw-Hill Companies. 2008; p. 2186-2193.

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