New curcumin analog, CCA-1.1, synergistically improves the antiproliferative effect of doxorubicin against T47D breast cancer cells
Keywords:
cell cycle, apoptosis, T47D cells, breast cancer, New curcumin analog (CCA-1.1)
Abstract
An improved compound of pentagamavunone-1 (PGV-1), chemoprevention-curcumin analog 1.1 (CCA-1.1), has been synthesized and proven to have antiproliferative effects against breast cancer cells. This study is designed to investigate the potency of CCA-1.1 alone and in combination with doxorubicin (Dox) on T47D cells in comparison with that of PGV-1. We used the MTT assay to assess cytotoxic activity. Propidium iodide (PI), annexin-V–PI, and DCFDA staining were respectively used to determine cell cycle profiles, apoptosis, and intracellular reactive oxygen species (ROS) levels. Senescent cells were identified using the SA-b-galactosidase assay. Our results revealed that CCA-1.1 possesses cytotoxic effects similar to those of PGV-1 on T47D cells. Synergistic effects during co-treatment with Dox were also observed. CCA-1.1 arrested cell cycle progression at the G2/M phase and limited sub-G1 accumulation, which is correlated with apoptosis. CCA-1.1 alone and in combination with Dox increased senescence and intracellular ROS to a similar level to those achieved by PGV-1. CCA-1.1 alone and in combination with Dox enhanced cytotoxic activity toward T47 cells compared to PGV-1. Thus, this curcumin analog may be a potential chemotherapeutic/co-chemotherapeutic candidate for estrogen receptor-positive (ER+) breast cancer therapy.
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Utomo, R. Y., Wulandari, F., Novitasari, D., Lestari, B., Susidarti, R. A., Jenie, R. I., Kato, J., Sardjiman, & Edy Meiyanto. (2020). Preparation and cytotoxic evaluation of PGV-1 derivative, CCA-1.1, as a new curcumin analog with improved-physicochemical and pharmacological properties. Manuscript Submitted for Publication.
Wulandari, F., Novitasari, D., Ikawati, M., Kirihata, M., Kato, J.-Y., & Meiyanto, E. (2020). A New Curcumin Analog, CCA-1.1, Induces Cell Death and Cell Cycle Arrest in WiDr Colon Cancer Cells via ROS Generation. Submitted for publication.
Yu, S., Kim, T., Yoo, K. H., & Kang, K. (2017). The T47D cell line is an ideal experimental model to elucidate the progesterone-specific effects of a luminal A subtype of breast cancer. Biochemical and Biophysical Research Communications, 486(3), 752–758. https://doi.org/10.1016/j.bbrc.2017.03.114
Zhao, M. L., Rabiee, A., Kovary, K. M., Bahrami-Nejad, Z., Taylor, B., & Teruel, M. N. (2019). Molecular competition in G1 controls when cells simultaneously commit to terminally differentiate and exit the cell-cycle [Preprint]. Cell Biology. https://doi.org/10.1101/632570
Baar, M. P., Brandt, R. M. C., Putavet, D. A., Klein, J. D. D., Derks, K. W. J., Bourgeois, B. R. M., Stryeck, S., Rijksen, Y., van Willigenburg, H., Feijtel, D. A., van der Pluijm, I., Essers, J., van Cappellen, W. A., van IJcken, W. F., Houtsmuller, A. B., Pothof, J., de Bruin, R. W. F., Madl, T., Hoeijmakers, J. H. J., … de Keizer, P. L. J. (2017). Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Cell, 169(1), 132-147.e16. https://doi.org/10.1016/j.cell.2017.02.031
Bandyopadhyay, A., Wang, L., Agyin, J., Tang, Y., Lin, S., Yeh, I.-T., De, K., & Sun, L.-Z. (2010). Doxorubicin in Combination with a Small TGFb Inhibitor: A Potential Novel Therapy for Metastatic Breast Cancer in Mouse Models. PLoS ONE, 5(4), 13. https://doi.org/10.1371/journal.pone.0010365
Bates, D., & Eastman, A. (2017). Microtubule destabilising agents: Far more than just antimitotic anticancer drugs: MDA mechanisms of action. British Journal of Clinical Pharmacology, 83(2), 255–268. https://doi.org/10.1111/bcp.13126
Chen, Z. J., & Ni, Z. (2006). Mechanisms of genomic rearrangements and gene expression changes in plant polyploids. BioEssays, 28(3), 240–252. https://doi.org/10.1002/bies.20374
Da’i, M., Jenie, U. A., AM, S., Kawaichi, M., & Meiyanto, E. (2007). T47D cells arrested at G2M and Hyperploidy Formation Induced by a Curcumin’s Analogue PGV-1. Indonesian Journal of Biotechnology, 12(2), 1005–1012. https://doi.org/10.22146/ijbiotech.7776
Darzynkiewicz, Z., Bedner, E., & Smolewski, P. (2001). Flow Cytometry in Analysis of Cell Cycle and Apoptosis. Seminars in Hematology, 38(2), 179–193. https://doi.org/10.1052/shem.2001.21929
Fernandez, P., Burghardt, R., Smith, R., Nodland, K., & Safe, S. (1994). High passage T47D human breast cancer cells: Altered endocrine and 2,3,7,8-tetrachlorodibenzo-p-dioxin responsiveness. European Journal of Pharmacology: Environmental Toxicology and Pharmacology, 270(1), 53–65. https://doi.org/10.1016/0926-6917(94)90080-9
Griffith, O. L., Spies, N. C., Anurag, M., Griffith, M., Luo, J., Tu, D., Yeo, B., Kunisaki, J., Miller, C. A., Krysiak, K., Hundal, J., Ainscough, B. J., Skidmore, Z. L., Campbell, K., Kumar, R., Fronick, C., Cook, L., Snider, J. E., Davies, S., … Ellis, M. J. (2018). The prognostic effects of somatic mutations in ER-positive breast cancer. Nature Communications, 9(1), 3476. https://doi.org/10.1038/s41467-018-05914-x
Hermawan, A., Fitriasari, A., Junedi, S., Ikawati, M., Haryanti, S., Widaryanti, B., Da’i, M., & Meiyanto, E. (2011). PGV-0 and PGV-1 Increased Apoptosis Induction of Doxorubicin on MCF-7 Breast Cancer Cells. PHARMACON, 12(2), 55–59. https://doi.org/10.23917/pharmacon.v12i2.32
Holliday, D. L., & Speirs, V. (2011). Choosing the right cell line for breast cancer research. Breast Cancer Research, 13(4). https://doi.org/10.1186/bcr2889
Kao, J., Salari, K., Bocanegra, M., Choi, Y.-L., Girard, L., Gandhi, J., Kwei, K. A., Hernandez-Boussard, T., Wang, P., Gazdar, A. F., Minna, J. D., & Pollack, J. R. (2009). Molecular Profiling of Breast Cancer Cell Lines Defines Relevant Tumor Models and Provides a Resource for Cancer Gene Discovery. PLoS ONE, 4(7), e6146. https://doi.org/10.1371/journal.pone.0006146
Kelly, P., Ma, Z., Baidas, S., Moroose, R., Shah, N., Dagan, R., Mamounas, E., & Rineer, J. (2017). Patterns of Progression in Metastatic Estrogen Receptor Positive Breast Cancer: An Argument for Local Therapy. International Journal of Breast Cancer, 2017, 1–8. https://doi.org/10.1155/2017/1367159
Lal, S., McCart Reed, A. E., de Luca, X. M., & Simpson, P. T. (2017). Molecular signatures in breast cancer. Methods, 131, 135–146. https://doi.org/10.1016/j.ymeth.2017.06.032
Larasati, Y. A., Yoneda-Kato, N., Nakamae, I., Yokoyama, T., Meiyanto, E., & Kato, J. (2018). Curcumin targets multiple enzymes involved in the ROS metabolic pathway to suppress tumor cell growth. Scientific Reports, 8(1). https://doi.org/10.1038/s41598-018-20179-6
Lee, S. J., & Langhans, S. A. (2012). Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis. BMC Cancer, 12(1), 44. https://doi.org/10.1186/1471-2407-12-44
Lestari, B., Nakamae, I., Yoneda-Kato, N., Morimoto, T., Kanaya, S., Yokoyama, T., Shionyu, M., Shirai, T., Meiyanto, E., & Kato, J. (2019). Pentagamavunon-1 (PGV-1) inhibits ROS metabolic enzymes and suppresses tumor cell growth by inducing M phase (prometaphase) arrest and cell senescence. Scientific Reports, 9(1), 14867. https://doi.org/10.1038/s41598-019-51244-3
Meiyanto, E., Agustina, D., Am, S., & Da’i, M. (2007). PGV-0 Induces Apoptosis on T47d Breast Cancer Cell Line Through Caspase-3 Activation. Jurnal Kedokteran Yarsi, 2, 11.
Meiyanto, E., Putri, D. D. P., Susidarti, R. A., Murwanti, R., Sardjiman, S., Fitriasari, A., Husnaa, U., Purnomo, H., & Kawaichi, M. (2014). Curcumin and its Analogues (PGV-0 and PGV-1) Enhance Sensitivity of Resistant MCF-7 Cells to Doxorubicin through Inhibition of HER2 and NF-kB Activation. Asian Pacific Journal of Cancer Prevention, 15(1), 179–184. https://doi.org/10.7314/APJCP.2014.15.1.179
Meiyanto, E., Putri, H., Larasati, Y. A., Utomo, R. Y., Jenie, R. I., Ikawati, M., Lestari, B., Yoneda-Kato, N., Nakamae, I., Kawaichi, M., & Kato, J.-Y. (2019). Anti-proliferative and Anti-metastatic Potential of Curcumin Analogue, Pentagamavunon-1 (PGV-1), Toward Highly Metastatic Breast Cancer Cells in Correlation with ROS Generation. Advanced Pharmaceutical Bulletin, 9(3), 445–452. https://doi.org/10.15171/apb.2019.053
Meiyanto, E., Septisetyani, E. P., Larasati, Y. A., & Kawaichi, M. (2018). Curcumin Analog Pentagamavunon-1 (PGV-1) Sensitizes Widr Cells to 5-Fluorouracil through Inhibition of NF-κB Activation. Asian Pacific Journal of Cancer Prevention, 19(1), 49–56. https://doi.org/10.22034/APJCP.2018.19.1.49
Nakamae, I., Morimoto, T., Shima, H., Shionyu, M., Fujiki, H., Yoneda-Kato, N., Yokoyama, T., Kanaya, S., Kakiuchi, K., Shirai, T., Meiyanto, E., & Kato, J. (2019). Curcumin Derivatives Verify the Essentiality of ROS Upregulation in Tumor Suppression. Molecules, 24(22), 4067. https://doi.org/10.3390/molecules24224067
Otto, S. P. (2007). The Evolutionary Consequences of Polyploidy. Cell, 131(3), 452–462. https://doi.org/10.1016/j.cell.2007.10.022
Pozarowski, P., & Darzynkiewicz, Z. (2004). Analysis of Cell Cycle by Flow Cytometry. In A. H. Sch�nthal, Checkpoint Controls and Cancer (Vol. 281, pp. 301–312). Humana Press. https://doi.org/10.1385/1-59259-811-0:301
Ray, P. D., Huang, B.-W., & Tsuji, Y. (2012). Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cellular Signalling, 24(5), 981–990. https://doi.org/10.1016/j.cellsig.2012.01.008
Reynolds, C. P., & Maurer, B. J. (2005). Evaluating Response to Antineoplastic Drug Combinations in Tissue Culture Models. In R. D. Blumenthal, Chemosensitivity (Vol. 110, pp. 173–184). Humana Press. https://doi.org/10.1385/1-59259-869-2:173
Shah, M. A., & Schwartz, G. K. (2001). Cell Cycle-mediated Drug Resistance: An Emerging Concept in Cancer Therapy. 7, 2168–2181. https://clincancerres.aacrjournals.org/content/7/8/2168.full-text.pdf
Tacar, O., Sriamornsak, P., & Dass, C. R. (2013). Doxorubicin: An update on anticancer molecular action, toxicity and novel drug delivery systems: Doxorubicin cell and molecular biological activity. Journal of Pharmacy and Pharmacology, 65(2), 157–170. https://doi.org/10.1111/j.2042-7158.2012.01567.x
Utomo, R. Y., Wulandari, F., Novitasari, D., Lestari, B., Susidarti, R. A., Jenie, R. I., Kato, J., Sardjiman, & Edy Meiyanto. (2020). Preparation and cytotoxic evaluation of PGV-1 derivative, CCA-1.1, as a new curcumin analog with improved-physicochemical and pharmacological properties. Manuscript Submitted for Publication.
Wulandari, F., Novitasari, D., Ikawati, M., Kirihata, M., Kato, J.-Y., & Meiyanto, E. (2020). A New Curcumin Analog, CCA-1.1, Induces Cell Death and Cell Cycle Arrest in WiDr Colon Cancer Cells via ROS Generation. Submitted for publication.
Yu, S., Kim, T., Yoo, K. H., & Kang, K. (2017). The T47D cell line is an ideal experimental model to elucidate the progesterone-specific effects of a luminal A subtype of breast cancer. Biochemical and Biophysical Research Communications, 486(3), 752–758. https://doi.org/10.1016/j.bbrc.2017.03.114
Zhao, M. L., Rabiee, A., Kovary, K. M., Bahrami-Nejad, Z., Taylor, B., & Teruel, M. N. (2019). Molecular competition in G1 controls when cells simultaneously commit to terminally differentiate and exit the cell-cycle [Preprint]. Cell Biology. https://doi.org/10.1101/632570
Published
2020-12-07
How to Cite
Wulandari, F., Ikawati, M., Novitasari, D., Kirihata, M., Kato, J.- ya, & 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(4), 244-256. https://doi.org/10.22146/ijp.681
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