Uji Sitotoksitas dan Hambatan Ekspresi VEGF pada Sel 4T1 Minyak Atsiri Rimpang Curcuma mangga Val.

Nurul Mukhlisa; Retno S. Sudibyo; Retno Murwanti

doi:10.21831/jps.v26i2.41386

Uji Sitotoksitas dan Hambatan Ekspresi VEGF pada Sel 4T1 Minyak Atsiri Rimpang Curcuma mangga Val.

Nurul Mukhlisa, Universitas Gadjah Mada, Indonesia
Retno S. Sudibyo, Universitas Gadjah Mada, Indonesia
Retno Murwanti, Universitas Gadjah Mada, Indonesia

10.21831/jps.v26i2.41386

Abstract

TNBC (Triple Negative Breast Cancer) merupakan kanker payudara yang paling ganas dengan resiko kambuh dan metastasis yang tinggi. Terapi yang efektif untuk pasien TNBC adalah menggunakan kemoterapi, namun banyak pasien mengalami drug resistant yang dapat meningkatkan mortalitas. TNBC bersifat metastasis ke organ tubuh lain yang ditandai dengan terjadinya angiogenesis. VEGF merupakan salah satu faktor angiogenik sehingga studi hambatan ekspresi protein tersebut dapat digunakan sebagai target pengembangan obat anti TNBC. Rimpang Curcuma mangga Val. digunakan masyarakat Yogyakarta sebagai herbal antikanker payudara, dan minyak atsirinya bersifat sitotoksik terhadap sel kanker payudara T47D dan MCF-7; namun belum terbukti sitotoksik terhadap sel TNBC. Penelitian ini bertujuan untuk melihat potensi antikanker TNBC minyak atsiri rimpang C. mangga Val. melalui uji sitotoksisitasnya terhadap sel 4T1 dengan kontrol positif alpelisib dan penghambatannya pada ekspresi protein VEGF. Hasil penelitian menunjukkan IC50 alpelisib terhadap sel kanker 4T1 adalah 32,975 µg/ml; sedangkan IC50 minyak atrisi C. mangga Val. adalah 91,96 µg/ml. Tidak ada perbedaan signifikan aktivitas penghambatan ekspresi protein VEGF antara minyak atsiri C. mangga Val dan alpelisib. Dapat disimpulkan bahwa minyak atsiri C. mangga Val. memiliki potensi antikanker payudara triple negative.

CYTOTOXICITY AND VEGF - EXPRESSION INHIBITION TESTS OF C. mangga Val. ESSENTIAL OIL ON 4T1 CELLS

TNBC (Triple Negative Breast Cancer) is the most malignant of breast cancer with high risk of recurrence and metastasis. The most effective therapy for TNBC patients is chemotherapy. However, many patients experienced with the drug resistant which increases of the mortality risk. TNBC is metastatic to other organs with indicated by angiogenesis process. VEGF is an angiogenic-factor-protein, so inhibition of its expression can be used as a target for anti-TNBC drug development. Curcuma mangga Val. rhizomes are widely used in Yogyakarta as an herbal anti-breast cancer. Research showed that the essential oil of C. mangga Val. had cytotoxic activity on T47D and MCF7 cells. However, there is no cytotoxic activity research on TNBC yet. This study is to determine the TNBC-anticancer potency of C. mangga Val. essential oil through its cytotoxic activity towards 4T1-breast cancer cells with alpelisib as the positive control, and its inhibition of VEGF-protein expression. The results showed the alpelisib’s IC50 was 32.975 µg/ml; while C. mangga Val. oil’s IC50 was 91,96 µg/ml against 4T1-breast cancer cells. There was no significantly different of VEGF-expression inhibition between C. mangga Val. oil and alpelisib. It could be concluded that C. mangga Val. essential oil at a potency of anti-triple negative breast cancer.

Keywords

Curcuma mangga Val., Triple Negative Breast Cancer, VEGF, 4T1

Full Text:

PDF

References

Anders, C. K., & Carey, L. A. (2009). Biology, metastatic patterns, and treatment of patients with triple-negative breast cancer. Clinical Breast Cancer, 9, S73-S81.

Astuti, E. (2015). Selektivitas dan mekanisme molekuler antikanker ekstrak aktif rimpang Curcuma mangga Val. (Disertasi tidak diterbitkan). Universitas Gadjah Mada.

Bauer, K. R., Brown, M., Cress, R. D., Parise, C. A., & Caggiano, V. (2007). Descriptive analysis of estrogen receptor (ER)‐negative, progesterone receptor (PR)‐negative, and HER2‐negative invasive breast cancer, the so‐called triple‐negative phenotype: A population‐based study from the California Cancer Registry. Cancer, 109(9), 1721-1728.

Bianchini, G., Balko, J. M., Mayer, I. A., Sanders, M. E., & Gianni, L. (2016). Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nature Reviews Clinical Oncology, 13(11), 674-690. doi: 10.1038/nrclinonc.2016.66.

Campbell, P. M., & Der, C. J. (2004). Oncogenic Ras and its role in tumor cell invasion and metastasis. Dalam Seminars in cancer biology, 14(2), 105-114.

Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: The next generation. Cell., 144(5), 646–674.

Khandelwal, S., Boylan, M., Spallholz, J. E., & Gollahon, L. (2018). Cytotoxicity of selenium immunoconjugates against triple negative breast cancer cells. International Journal of Molecular Sciences, 19(11), 3352.

Lehmann, B. D., Bauer, J. A., Chen, X., Sanders, M. E., Chakravarthy, A. B., Shyr, Y., & Pietenpol, J. A. (2011). Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. The Journal of Clinical Investigation, 121(7), 2750-2767. doi: 10.1172/JCI45014.

Liu, Y., Zhao, L., Li, D., Yin, Y., Zhang, C. Y., Li, J., & Zhang, Y. (2013). Microvesicle-delivery miR-150 promotes tumori-genesis by up-regulating VEGF, and the neutralization of miR-150 attenuate tumor development. Protein & Cell, 4(12), 932-941.

Parveen, A., Akash, M. S. H., Rehman, K., & Kyunn, W. W. (2016). Dual role of p21 in the progression of cancer and its treatment. Critical Reviews™ in Eukaryotic Gene Expression, 26(1), 49-61. doi: 10.1615/CritRevEukaryotGeneExpr.v26.i1.60.

Ribatti, D., Nico, B., Ruggieri, S., Tamma, R., Simone, G., & Mangia, A. (2016). Angiogenesis and antiangiogenesis in triple-negative breast cancer. Translational Oncology, 9(5), 453-457.

Skehan, P., Storeng, R., Scudiero, D., Monks, A., McMahon, J., Vistica, D., Warren, J. T., Bokesch, H., Kenney, S., & Boyd, M. R. (1990). New colorimetric cytotoxicity assay for anticancer-drug screening. JNCI: Journal of the National Cancer Institute, 82(13), 1107-1112.

Sudibyo R. S. (2021). Uji sitotoksisitas dan molecular docking antikanker payudara jalur Era dan VEGF kandungan senyawa ekstrak heksan dan minyak atsiri rimpang Curcuma mangga Val. (Laporan penelitian tidak diterbitkan). Fakultas Farmasi Universitas Gadjah Mada.

Sudibyo, R. S., Sudarmanto, A., Mahdi, L., & Khudzifi, M. (2020). Pharmacophore mapping and molecular docking analysis of essential oil compounds from Curcuma mangga Val. rhizome against erα, and the cytotoxic effect on MCF 7 Cells. Indonesian Journal of Pharmacy (Reviewed, 2021).

Sudibyo, R. S., & Taryono. (2020). Increasing anticancer substances and the cytotoxicity test on T47D using fertilization and induction on Curcuma mango Val. Jurnal Penelitian Saintek 25(1), 1-10.

Verret, B., Cortes, J., Bachelot, T., Andre, F., & Arnedos, M. (2019). Efficacy of PI3K inhibitors in advanced breast cancer. Annals of Oncology, 30, x12-x20.

Yan, C., & Boyd, D. D. (2007). Regulation of matrix metalloproteinase gene expression. Journal of Cellular Physiology, 211(1), 19-26.

Zampieri, L., Bianchi, P., Ruff, P., & Arbuthnot, P. (2002). Differential modulation by estradiol of P-glycoprotein drug resistance protein expression in cultured MCF7 and T47D breast cancer cells. Anticancer Research, 22(4), 2253-2259.

DOI: https://doi.org/10.21831/jps.v26i2.41386