Antimigratory Evaluation from Curcumin-Derived Synthetic Compounds PGV-1 and CCA-1.1 on HCC1954 and MDA-MB-231 Cells

Dhania Novitasari; Edy Meiyanto; Jun-ya Kato; Riris Istighfari Jenie

doi:10.14499/indonesianjcanchemoprev13iss2pp71-82

Antimigratory Evaluation from Curcumin-Derived Synthetic Compounds PGV-1 and CCA-1.1 on HCC1954 and MDA-MB-231 Cells

Dhania Novitasari, Edy Meiyanto, Jun-ya Kato, Riris Istighfari Jenie

Abstract

Earlier findings reported the anticancer-mediated activities of curcumin-modified compounds Pentagamavunone-1 (PGV-1) and Chemoprevention Curcumin Analog 1.1 (CCA-1.1) with several mechanisms including cell cycle arrest, reactive oxygen species (ROS) production, and cell migration disruption. Our study aims to evaluate the antimigratory activity of PGV-1 and CCA-1.1 on aggressive breast cancer cell lines (MDA-MB-231 and HCC1954 cells) and their effect on HER2 protein. The trypan blue exclusion method was conducted for the antiproliferative effect. The PGV-1 or CCA-1.1 effect on cell migration was determined by wound healing assay. Using gelatin zymography, we checked the secretion level of matrix metalloproteinase (MMP). We also evaluated the human epidermal growth receptor-2 (HER2) level after incubation with PGV-1 or CCA-1.1 in HCC1954 cells by western blot. Based on the antiproliferation assay, MDA-MB-231 and HCC1954 cells were sensitive to PGV-1 and CCA-1.1. MMP-2 was only observed in HCC1954 cells while MMP-9 was only observed in MDA-MB-231. Both PGV-1 and CCA-1.1 significantly suppressed MMP-9 activity in MDA-MB-231 cells. Moreover, PGV-1 inhibited HER2 protein levels in HCC1954 although it was not significant, whereas CCA-1.1 did not affect HER2 protein. This study strengthens the scientific evidence for PGV-1 and CCA-1.1 activities for future exploration as candidate chemotherapy with multitarget against breast cancer.

Keywords: Curcumin analog, cell migration, MMP-9, HER2, breast cancer.

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References

Appert-Collin, A., Hubert, P., Crémel, G., and Bennasroune, A., 2015, Role of ErbB Receptors in Cancer Cell Migration and Invasion, Frontiers in Pharmacology, 6. CrossRef

Bose, R., Molina, H., Patterson, A.S., Bitok, J.K., Periaswamy, B., Bader, J.S., et al., 2006, Phosphoproteomic analysis of Her2/neu signaling and inhibition, PNAS, 103, 9773–9778. CrossRef

Di, J., Huang, H., Qu, D., Tang, J., Cao, W., Lu, Z., et al., 2015, Rap2B promotes proliferation, migration, and invasion of human breast cancer through calcium-related ERK1/2 signaling pathway, Sci Rep, 5, 12363. CrossRef

Fragomeni, S.M., Sciallis, A., and Jeruss, J.S., 2018, Molecular subtypes and local-regional control of breast cancer, Surg Oncol Clin N Am, 27, 95–120. CrossRef

Freudenberg, J.A., Wang, Q., Katsumata, M., Drebin, J., Nagatomo, I., and Greene, M.I., 2009, The role of HER2 in early breast cancer metastasis and the origins of resistance to HER2-targeted therapies, Exp Mol Pathol, 87, 1–11. CrossRef

Grada, A., Otero-Vinas, M., Prieto-Castrillo, F., Obagi, Z., and Falanga, V., 2017, Research Techniques Made Simple: Analysis of Collective Cell Migration Using the Wound Healing Assay, Journal of Investigative Dermatology, 137, e11–e16. CrossRef

Hermawan, A., Fitriasari, A., Junedi, S., Ikawati, M., Haryanti, S., Widaryanti, B., et al., 2011, PGV-0 and PGV-1 increased apoptosis induction of doxorubicin on MCF-7 breast cancer cells, Pharmacon, 12, 55–59. CrossRef

Johnson, E., Seachrist, D.D., DeLeon-Rodriguez, C.M., Lozada, K.L., Miedler, J., Abdul-Karim, F.W., and Keri, R.A., 2010, HER2/ErbB2-induced Breast Cancer Cell Migration and Invasion Require p120 Catenin Activation of Rac1 and Cdc42, J Biol Chem, 285, 29491–29501. CrossRef

Kim, S., Lee, J., Jeon, M., Lee, J.E., and Nam, S.J., 2016, Zerumbone suppresses the motility and tumorigenecity of triple negative breast cancer cells via the inhibition of TGF-β1 signaling pathway, Oncotarget, 7, 1544–1558. CrossRef

Kolditz, F., Krausze, J., Heinz, D.W., Niemann, H.H., and Müller-Goymann, C.C., 2014, Wound healing potential of a dimeric InlB variant analyzed by in vitro experiments on re-epithelialization of human skin models, European Journal of Pharmaceutics and Biopharmaceutics, Theme Issue:Dermal and Transdermal Drug Delivery, 86, 277–283. CrossRef

Lestari, B., Nakamae, I., Yoneda-Kato, N., Morimoto, T., Kanaya, S., Yokoyama, T., et al., 2019, Pentagamavunon-1 (PGV-1) inhibits ROS metabolic enzymes and suppresses tumor cell growth by inducing M phase (prometaphase) arrest and cell senescence, Sci Rep, 9, 1–12. CrossRef

Li, H., Qiu, Z., Li, F., and Wang, C., 2017, The relationship between MMP-2 and MMP-9 expression levels with breast cancer incidence and prognosis, Oncol Lett, 14, 5865–5870. CrossRef

Lv, Y., Zhao, X., Zhu, L., Li, S., Xiao, Q., He, W., and Yin, L., 2018, Targeting intracellular MMPs efficiently inhibits tumor metastasis and angiogenesis, Theranostics, 8, 2830–2845. CrossRef

Marra, A., Trapani, D., Viale, G., Criscitiello, C., and Curigliano, G., 2020, Practical classification of triple-negative breast cancer: intratumoral heterogeneity, mechanisms of drug resistance, and novel therapies, NPJ Breast Cancer, 6, 1–16. CrossRef

Meiyanto, E., Husnaa, U., Kastian, R.F., Putri, H., Larasati, Y.A., Khumaira, A., et al., 2021, The Target Differences of Anti-Tumorigenesis Potential of Curcumin and its Analogues Against HER-2 Positive and Triple-Negative Breast Cancer Cells, Adv Pharm Bull, 11, 188–196. CrossRef

Meiyanto, E., Novitasari, D., Utomo, R.Y., Susidarti, R.A., Putri, D.D.P., and Kato, J., 2022, Bioinformatic and Molecular Interaction Studies Uncover That CCA-1.1 and PGV-1 Differentially Target Mitotic Regulatory Protein and Have a Synergistic Effect against Leukemia Cells, Indonesian Journal of Pharmacy, 33(2), 225-233. CrossRef

Meiyanto, E., Putri, H., Larasati, Y.A., Utomo, R.Y., Jenie, R.I., Ikawati, M., et al., 2019, Antiproliferative and Anti-Metastatic Potential of Curcumin Analogue, Pentagamavunon-1 (PGV-1), Toward Highly Metastatic Breast Cancer Cells in Correlation With ROS Generation, Adv Pharm Bull, 9, 445–452. CrossRef

Novitasari, D., Handayani, S., and Jenie, R.I., 2018, Ethanolic Extract of Hedyotis corymbosa L. Inhibits Migration and MMP-9 Activity on Metastatic Breast Cancer Cells, Indonesian Journal of Cancer Chemoprevention, 9, 16–22. CrossRef

Novitasari, D., Jenie, R.I., Utomo, R.Y., Kato, J.Y., and Meiyanto, E., 2021a, CCA-1.1, a Novel Curcumin Analog, Exerts Cytotoxic anti- Migratory Activity toward TNBC and HER2-Enriched Breast Cancer Cells, Asian Pac J Cancer Prev, 22, 1827–1836. CrossRef

Novitasari, D., Jenie, R.I., Wulandari, F., Putri, D.D.P., Kato, J., and Meiyanto, E., 2021b, A Curcumin Like Structure (CCA-1.1) Induces Permanent Mitotic Arrest (Senescence) on Triple Negative Breast Cancer (TNBC) Cells, 4T1, Res J Pharm Technol, 14, 4375–4382. CrossRef

Novitasari, D., Wulandari, F., Jenie, R.I., Utomo, R.Y., Kato, J.-Y., and Meiyanto, E., 2021c, A new curcumin analog, CCA-1.1, induces cell cycle arrest and senescence toward ER-positive breast cancer cells, International Journal of Pharmaceutical Research, 13, 1–9. CrossRef

Rakha, E.A., and Chan, S., 2011, Metastatic Triple-negative Breast Cancer, Clinical Oncology, 23, 587–600. CrossRef

Sangrar, W., Shi, C., Mullins, G., LeBrun, D., Ingalls, B., and Greer, P.A., 2015, Amplified Ras-MAPK signal states correlate with accelerated EGFR internalization, cytostasis and delayed HER2 tumor onset in Fer-deficient model systems, Oncogene, 34, 4109–4117. CrossRef

Schettini, F. and Prat, A., 2021, Dissecting the biological heterogeneity of HER2-positive breast cancer, Breast, 59, 339–350. CrossRef

Turashvili, G., and Brogi, E., 2017, Tumor Heterogeneity in Breast Cancer, Frontiers in Medicine, 4. CrossRef

Utomo, R.Y., Wulandari, F., Novitasari, D., Lestari, B., Susidarti, R.A., Jenie, R.I., et al., 2022, Preparation and cytotoxic evaluation of PGV-1 derivative, CCA-1.1, as a new curcumin analog with improved physicochemical and pharmacological properties, Advanced Pharmaceutical Bulletin, 12(3), 603-612. CrossRef

Wulandari, F., Ikawati, M., Novitasari, D., Kirihata, M., Kato, J., and Meiyanto, E., 2020, New curcumin analog, CCA-1.1, synergistically improves the antiproliferative effect of doxorubicin against T47D breast cancer cells, Indonesian Journal of Pharmacy, 31, 244–256. CrossRef

Yousef, E.M., Tahir, M.R., St-Pierre, Y., and Gaboury, L.A., 2014, MMP-9 expression varies according to molecular subtypes of breast cancer, BMC Cancer, 14, 609. CrossRef

Zhang, W., Wang, F., Xu, P., Miao, C., Zeng, X., Cui, X., et al., 2014, Perfluorooctanoic acid stimulates breast cancer cells invasion and up-regulates matrix metalloproteinase-2/-9 expression mediated by activating NF-κB, Toxicol Lett, 229, 118–125. CrossRef