Efektivitas Ekstrak Artemisia vulgaris sebagai Suplementasi terhadap Kemoterapi Adenokarsinoma Mammae dalam Meningkatkan IL-12 dan Indeks Apoptosis Sel Kanker (Studi pada Mencit C3H yang Diberi Regimen Kemoterapi Adriamycin-Cyclophosphamide)
DOI:
https://doi.org/10.21776/ub.jkb.2018.030.02.1Keywords:
Adenokarsinoma mammae, Artemisia vulgaris, imunoterapi, indeks apoptosis, kadar IL-12Abstract
Insiden kanker payudara di seluruh dunia masih tinggi. Pembedahan tetap merupakan pilihan utama dengan modalitas lain berupa kemoterapi, radiasi, dan imunoterapi antara lain Artemisia vulgaris (AV). Penelitian dilakukan untuk membuktikan efek pemberian ekstrak AV terhadap kadar IL-12 dan indeks apoptosis sel kanker pada adenokarsinoma mammae. Penelitian ini menggunakan desain post test only control group design menggunakan 24 ekor mencit C3H betina yang dibagi secara acak menjadi empat kelompok, yaitu: K (kontrol), P1 (kemoterapi), P2 (ekstrak AV), dan P3 (kombinasi kemoterapi dan ekstrak AV). Adriamycin 0,18mg dan Cyclophosphamide 1,8mg diberikan sebanyak 2 siklus. Ekstrak AV diberikan 13mg (0,2ml) perhari. Kadar IL-12 dinilai dengan pengecatan imunohistokimia sedangkan indeks apoptosis dengan hematoxilin eosin. Rerata kadar IL-12 dan indeks apoptosis didapatkan K, P1, P2, P3 berturut-turut 60,28+1,54, 50,40+1,56, 75,40+1,46, 53,48+1,35 dan 2,18+0,80, 18,00+1,58, 3,34+0,51, 20,32+1,39. Analisis statistik menunjukkan terdapat perbedaan bermakna pada kadar IL-12 antara kelompok K vs P1, P2, P3 (p=0,001), P1 vs P2 (p=0,001), P1 vs P3 (p=0,028), P2 vs P3 (p=0,001) dan indeks apoptosis antara kelompok K vs P1, P3 (p=0,001), P1 vs P2 (p=0,001), P1 vs P3 (p=0,035), P2 vs P3 (p=0,001). Terdapat hubungan positif kuat yang signifikan antara kadar IL-12 dengan indeks apoptosis (p=0,041 dan r=0,893). Pemberian ekstrak Artemisia vulgaris dapat meningkatkan kadar IL-12 dan indeks apoptosis sel kanker pada mencit C3H dengan adenokarsinoma mammae yang diberi regimen kemoterapi Adriamycin-Cyclophosphamide.
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References
Mugi W. Deteksi Dini Kanker Leher Rahim dan Kanker Payudara di Indonesia 2007-2014. Di dalam: Kementerian Kesehatan Republik Indonesia (Ed). Buletin Jendela Data dan Informasi Kesehatan. Jakarta: Kementerian Kesehatan Republik Indonesia; 2015: hal. 12-15.
Kementerian Kesehatan Republik Indonesia. Panduan Nasional Penanganan Kanker (Kanker Payudara). Jakarta: Komite Nasional Penanggulangan Kanker; 2015; hal. 1-10.
Roezin A. Perkembangan Mutakhir Tumor Ganas Payudara. Universa Medicina Fakultas Kedokteran Trisakti. 2005; 24(4): 190-198.
Luangdilok S, Samarnthai N, and Korphaisarn K. Association between Pathological Complete Response and Outcome Following Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients. Journal of Breast Cancer. 2014; 17(4): 376-385.
Das AK. Anticancer Effect of AntiMalarial Artemisinin Compounds. Annals of Medical and Health Science Research. 2015; 5(2): 93-102.
Riwanto I, Budijitno S, Dharmana E, et al. Effect of Phaleria macrocarpa Supplementation on Apoptosis and Tumor Growth of C3H Mice with Breast Cancer Under Treatment with Adriamycin-Cyclophosphamide. International Surgery. 2011; 96(2): 164-170
Majdalawieh AF and Fayyad MW. Recent Advances on the Anti-Cancer Properties of Nigella sativa, a Widely Used Food Additive. Journal of Ayurveda and Integrative Medicine. 2016; 7(3): 173-180.
Mbuthia KS, Mireji PO, Ngure RM, et al. Tea (Camellia sinensis) Infusions Ameliorate Cancer in 4TI Metastatic Breast Cancer Model. BMC Complementary and Alternative Medicine. 2017; 17(1): 202-214.
Abdulllah M, Syam AF, Meilany S, et al. The Value of Caspase-3 after the Application of Annona muricata Leaf Extract in COLO-205 Colorectal Cancer Cell Line. Gastroenterology Research and Practice. 2017; 2017: 1-5.
Choi E and Kim G. Effect of Artemisia Species on Cellular Proliferation and Apoptosis in Human Breast Cancer Cells via Estrogen Receptor Related Pathway. Journal of Traditional Chinese Medicine. 2013; 33(5): 658-663.
Sharmila K and Padma PR. Anticancer Activity of Artemisia vulgaris on Hepatocellular Carcinoma (HepG2) Cells. International Journal of Pharmacy and Pharmaceutical Sciences. 2013; 5(3): 479-483.
Saleh AM, Aljada A, Rizvi SA, Nasr A, Alaskar AS, and William JD. In Vitro Cytotoxicity of Artemisia vulgaris L. Essential Oil is Mediated by a Mitochondria-Dependent Apoptosis in HL-60 Leukemic Cell Line. BMC Complementary and Alternative Medicine. 2014; 14: 226-240.
Michaelsen FW, Saeed ME, Schwarzkopf J, and Efferth T. Activity of Artemisia annua and Artemisinin Derivates, in Prostate Carcinoma. Phytomedicine. 2015; 22(14): 1223-1231.
Haniya AK, dan Padma PR. Phytochemical Investigation of Methanolic Extract of Artemisia vulgaris L. leaves. International Journal of Pharma and Bio Sciences. 2014; 5(2): 184-195.
Aini N, Soebaktiningsih, Fitri LE, Kalsum U, dan Sumarno. Pengaruh Ekstrak Biji Nimba (Azadirachta indica) Terhadap Penurunan Derajat Parasit dan Jumlah Hemozoin pada Kultur Plasmodium falciparum. Jurnal Kedokteran Brawijaya. 2004; 20(3): 115-124.
Yance DR and Sagar SM. Targeting Angiogenesis with Integrative Cancer Therapies. Integrative Cancer Therapies. 2006; 5(1): 9-29.
Jia J, Qin Y, Zhang L, et al. Artemisinin Inhibits Gallbladder Cancer Cell Lines Through Triggering Cell Cycle Arrest and Apoptosis. Molecular Medicine Reports. 2016; 13(5): 4461-4468.
Lasek W, Zagozdzon R, and Jakobisiak M. Interleukin 12: Still a Promising Candidate for Tumor Immunotherapy? Cancer Immunology, Immunotherapy. 2014; 63(5): 419-435.
Melero I, Mazzolini G, Narvaiza I, Qian C, Chen L, and Prieto J. IL-12 Gene Therapy for Cancer: In Synergy with Other Immunotherapies. Trends in Immunology. 2001; 22(3): 113-115.
Alkayyal AA, Mahmoud AB, and Auer RC. Interleukin-23-expressing Oncolytic Virus: A Promising Strategy for Cancer Immunotherapy. Journal of Taibah University Medical Sciences. 2016; 11(3): 187-193.
Elmore S. Apoptosis: A Review of Programmed Cell Death. Toxicologic Pathology. 2007; 35(4): 495-516.
Hassan M, Watari H, AbuAlmaaty A, Ohba Y, and Sakuragi N. Apoptosis and Molecular Targeting Therapy in Cancer. BioMed Research International. 2014; 2014: 1-23.
World Health Organization. Research Guidelines for Evaluating the Safety and Efficacy of Herbal Medicine. (Online) 1993. http://apps.who.int/medicinedocs/en/d/Jh2946e/
Cho YC, Lee SH, Lee M, et al. Enhanced IL-12p40 Production in LPS-stimulated Macrophages by Inhibiting JNK Activation by Artemisinin. Archives of Pharmacal Research. 2012; 35(11): 1961-1968.
Langroudi L, Hassan ZM, Ebtekar M, Mahdavi M, Pakravan N, and Noori S. A Comparison of Low-Dose Cyclophosphamide Treatment with Artemisinin Treatment in Reducing the Number of Regulatory T Cells in Murine Breast Cancer. International Immunopharmacology. 2010; 10(9): 1055-1061.
Jankowitz RC, and Davidson NE. Breast Cancer. In: Boyiadzis MM, Frame JN, Kohler DR, and Fojo T (Eds). Hematology-Oncology Therapy 2nd edition. New York: McGraw-Hill Education; 2014: hal. 102.
Li Z, Li Q, Wu J, Wang M, and Yu J. Artemisinin and Its Derivates as a Repurposing Anticancer Agent: What Else Do We Need to Do? Molecules. 2016; 21(10): 1-14.
Blazquez AG, Fernandez M, Sanchez L, et al. Novel Artemisinin Derivates with Potential Usefulness against Liver/Colon Cancer and Viral Hepatitis. Bioorganic and Medicinal Chemistry. 2013; 21(14): 4432-4441.
Mu D, Zhang W, Chu D, et al. The Role of Calcium, P38 MAPK in Dihydroartemisinin-induced Apoptosis of Lung Cancer PC-14 Cells. Cancer Chemotheraphy and Pharmacology. 2008; 61(4): 639-645.
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