Anti-metastatic Activity of Curcumin Analog Pentagamaboronon-0-Sorbitol Against HER2-overexpressed MCF-7 Breast Cancer Cells

Lailatul Qodria, Indah Hairunisa, Rohmad Yudi Utomo, Adam Hermawan, Edy Meiyanto

Abstract


Breast cancer with Human Epidermal Growth Factor Receptor (HER)2 overexpression increases tumor progession and lead to metastasis, which is primarily cause of mortality in breast cancer. Pentagamaboronon-0 Sorbitol (PGB-0-So) is an aquoeous formulation of curcumin analog, PGB-0, with sorbitol. This compound has been developed as an anti-cancer chemotherapeutic agent and a boron carrying pharmaceutical for boron neutron capture therapy (BNCT). The aims of this study are to investigate antimetastatic activities of PGB-0-So against HER2-overexpressed MCF-7 breast cancer (MCF-7/HER2) cells. The MTT cytotoxicity assay of PGB-0-So exhibited cytotoxic effect with an IC50 value of 35 μM. The testing of anti-migration activity using the scratch wound healing assay demonstrated that PGB-0-So inhibited the closure of the wound on MCF-7/HER2 cells compare to the control. Furthermore, PGB-0-So was able to suppress matrix metalloproteinase (MMP)-9 activities, based on the gelatin zymography assay. In conclusion, PGB-0-So has potency to be developed as an anti-cancer agent against metastatic breast cancer.

Keywords : PGB-0-So, anti-metastatsis, cell migration, MMP-9, MCF-7/HER2


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Amalina, N.D., Nurhayati, I.P., and Meiyanto, E., 2017, Doxorubicin Induces Lamellipodia Formation and Cell Migration, Indones. J. Cancer Chemoprev., 8(2), 61–67. CrossRef

Bandyopadhyay, A., Wang, L., Agyin, J., Tang, Y., Lin, S., Yeh, I.T., et al., 2010, Doxorubicin in Combination with A Small TGFβ Inhibitor: A Potential Novel Therapy for Metastatic Breast Cancer in Mouse Models, PLoS One, 5(4), e10365. CrossRef

Bandyopadhyay, D., 2014, Farmer to Pharmacist: Curcumin as an Anti-invasive and Antimetastatic Agent for The Treatment of Cancer, Front. Chem., 2, 113. CrossRef

Baribeau, S., Chaudhry, P., Parent, S., and Asselin, É, 2014, Resveratrol Inhibits Cisplatin-induced Epithelial-to-mesenchymal Transition in Ovarian Cancer Cell Lines, PloS One, 9(1), e86987. CrossRef

Bhatnagar, B., Gilmore, S., Gloubeva, O., Pelser, C., Medeiros, M., Chumsri, S., et al., 2014, Chemotherapy Dose Reduction Due to Chemotherapy Induced Peripheral Neuropathy in Breast Cancer Patients Receiving Chemotherapy in the Neoadjuvantar Adjuvant Settings: A Single-center Experience, SpingerPlus, 3, 366. CrossRef

Carvalho, C., Santos, R.X., Cardoso, S., Correia, S., Oliveira, P.L., Santos, M.S., et al., 2009, Doxorubicin: The Good, The Bad and The Ugly Effect, Current Med. Chem., 16(25), 3267-3286. CrossRef

Kim, J.M., Noh, E.M., Kwon, K.B., Kim, J.S., You, Y.O., Hwang, J.K., et al., 2012, Curcumin Suppresses the TPA-induced Invasion Through Inhibition of PKCα-dependent MMP-expression in MCF7 Human Breast Cancer Cells, Phytomedicine, 19(12), 1085–1092. CrossRef

Kusumastuti, R., Meiyanto, E., and Jenie, R.I., 2016, ‘Dibenzilidine Boronic Acid Cyclopentanone (DBBAC) Potency as Chemotherapeutic Agent for Doxorubicin Through Apoptosis Induction, Cell Cycle Modulation, and Metastasis Inhibition Against 4T1 Cells’, Thesis, Yogyakarta: Universitas Gadjah Mada.

Luque-Cabal, M., García-Teijido, P., FernándezPérez, Y., Sánchez-Lorenzo, L., and PalacioVázquez, I., 2016, Mechanisms Behind theResistance to Trastuzumab in HER2-amplified Breast Cancer and Strategies to Overcome It., Clin. Med. Insights Oncol., 10(Suppl 1), 21-30. CrossRef

Lin, S.S., Lai, K.C., Hsu, S.C., Yang, J.S., Kuo, C.L., Lin, J.P., et al., 2009. Curcumin Inhibits the Migration and Invasion of Human A549 Lung Cancer Cells Through the Inhibition of Matrix Metalloproteinase-2 and -9 and Vascular Endothelial Growth Factor (VEGF), Cancer Letters, 285, 127–133. CrossRef

Meiyanto, E., Putri, D.D., Susidarti, R.A., Murwanti, R., Sardjiman, F.A., Husnaa, U., et al., 2014, Curcumin and Its Analogues (PGV-0 and PGV-1) Enhance Sensitivity of Resistant MCF-7 Cells to Doxorubicin Through Inhibition of HER2 and NFkB Activation, Asian Pac. J. Cancer Prev., 15(1), 179–184. CrossRef

Mosmann, T., 1983, Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays, J. Immunol. Methods, 65(1-2), 55–63. CrossRef

Nguyen, K.C.T., Muthiah, M., Islam, M.A., Kalash, R.S., Cho, C.S., Park, H., et al., 2014, Selective Transfection with Osmotically Active Sorbitol Modified PEI Nanoparticles for Enhanced Anti-cancer Gene Therapy, Colloids Surf. B. Biointerfaces, 119, 126–136. CrossRef

Nilsson, U.W., Garvin, S., and Dabrosin, C., 2007, MMP-2 and MMP-9 Activity is Regulated by Estradiol and Tamoxifen in Cultured Human Breast Cancer Cells, Breast Cancer Res. Treat., 102(3), 253-61. CrossRef

Patlolla, J.M., Swamy, M.V., Raju, J., and Rao, C.V., 2004, Overexpression of Caveolin-1 in Experimental Colon Adenocarcinomas and Human Colon Cancer Cell Lines, Oncology Rep., 11, 957–963. CrossRef

Putri, H., Jenie, R.I., Handayani, S., Kastian, R.F., and Meiyanto, E., 2016, Combination of Potassium Pentagamavunon-0 and Doxorubicin Induces Apoptosis and Cell Cycle Arrest and Inhibits Metastasis in Breast Cancer Cells, Asian Pac. J. Cancer Prev., 17(5), 2683–2688. Link

Shangguan, L., Chen, Q., Shi, B., and Huang, F., 2017, Enhancing the Solubility and Bioactivity of Anticancer Drug Tamoxifen by Water-soluble Pillar[6]arene-based Host–guest Complexation, Chem. Commun., 53(70), 9749–9752. CrossRef

Thorn, C.F., Oshiro, C., Marsh, S., HernandezBoussard, T., McLeod, H., Klein, T.T., et al., 2011, Doxorubicin Pathways: Pharmacodynamics and Adverse Effects, Pharmacogenet. Genomics., 21(7), 440-446. CrossRef

Utomo, R.Y., Putri, H., Pudjono, P., Susidarti, R.A., Jenie, R.I., and Meiyanto, E., 2017, Synthesis and Cytotoxic Activity of 2,5-bis(4-boronic acid)benzylidine Cyclopentanone on HER2 Overexpressed-cancer Cells, Indonesian J. Pharm., 28, 74. CrossRef

Waalkes, S., Eggers, H., Blasig, H., Atschekzei, F., Kramer, M.W., Hennenlotter, J., et al., 2011, Caveolin 1 mRNA is Overexpressed in Malignant Renal Tissue and Might Serve As a Novel Diagnostic Marker for Renal Cancer, Biomark Med., 5(2), 219–225. CrossRef

Wolf-Yadlin, A., Kumar, N., Zhang, Y., Hauteniemi, S., Zaman, M., Kim, H., et al., 2006, Effects of HER2 Overexpression on Cell Signalling Networks Governing Proliferation and Migration, Mol. Sys. Biol., 2, 54-68. CrossRef

Yokoyama, H., Ikehara, Y., Kodera, Y., Ikehara, S., Yatabe, Y., Mochizuki, Y., et al., 2006, Molecular Basis for Sensitivity and Acquired Resistance to Gefitinib in HER2-overexpressed Human Gastric Cancer Cell Lines Derived from Liver Metastasis, Br. J. Cancer, 95(11), 1504. CrossRef

Zong, H., Wang, F., Fan, Q., and Wang, L., 2012, Curcumin Inhibits Metastatic Progression of Breast Cancer Cell Through Suppression of Urokinase-type Plasminogen Activator by NFkappa B Signaling Pathways, Mol. Biol. Rep., 39(4), 4803–4808. CrossRef




DOI: http://dx.doi.org/10.14499/indonesianjcanchemoprev9iss3pp118-125

Copyright (c) 2018 Lailatul Qodria

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