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Cytotoxic Activity of Raphanus sativus Linn. on Selected Cancer Cell Lines and Mechanistic Pathways Predicted Through Mathematical Modeling

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Modelling, Simulation and Applications of Complex Systems (CoSMoS 2019)

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Abstract

Studies have shown different effects of Raphanus sativus L. (RS) extract on different cancer cell types. However, the dynamics of gene regulation between RS and cancer is still unknown. In this study, a mathematical model was incorporated to link cell cycle regulation pathways associated with the pharmacognosy of radish extracts towards breast cancer (BC), chronic myelogenous leukemia (CML), and colorectal cancer (CC). The cell cycle regulation pathways considered were MAPK/ERK and PI3K/Akt signaling pathways. A model created using ordinary differential equations was used to simulate the steady state concentrations of the proteins in both pathways, before and after exposure to radish extracts. Among the proteins ubiquitous in these pathways, Cyclin D1-CDK complex and p53 were found to be predominantly dysregulated in most cancers. The expression of these proteins was used as the benchmark of the pharmacognosy of radish extracts. Our simulation showed a decreasing trend in the binding specificities (\(K_M\)) of RS with Cyclin D1-CDK complex and p53 respectively from CML \(\left[ 5\,\upmu \mathrm{M}, 100 \,\upmu \mathrm{M}\right] \), CC \([2.5 \times 10^{-2}\,\upmu \mathrm{M}, 10\,\upmu \mathrm{M}]\) up to BC \([10^{-6}\,\upmu \mathrm{M}, 10^{-3}\,\upmu \mathrm{M}]\) which led to a decrease in Cyclin D1-CDK complex (90.74% for BC, 73.42% for CC, 1.10% for CML) and an increase in p53 (83.47% for BC, 62.75% for CC, 5.69% for CML). This suggests that the anticancer activity of RS was through the moderation of cell proliferation and induction of apoptosis in malignant neoplasms. Hence, the model proposed that RS had high chemotherapeutic activity on BC while having moderate efficacy on CC and insignificant efficacy on CML as substantiated by cytotoxicity assays on MCF-7 and HT-29 which both exhibited \(IC_{50} < 20~\upmu \)g/mL and K562 trials which gave \(IC_{50} > 100\,\upmu \)g/mL.

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Authors and Affiliations

  1. Mathematics and Statistics Department, De La Salle University, 2401 Taft Avenue, 0922, Manila, Philippines

    Angelyn Lao, Jan Marie Claire Edra & Kathleen Dane Talag

  2. Chemistry Department, De La Salle University, 2401 Taft Avenue, 0922, Manila, Philippines

    Daisylyn Senna Tan, Marissa Noel & Maria Carmen Tan

  3. Molecular Science Unit Laboratory, Center for Natural Sciences and Environmental Research (CENSER), De La Salle University, 2401 Taft Avenue, 0922, Manila, Philippines

    Glenn Oyong

  4. Biology Department, De La Salle University, 2401 Taft Avenue, 0922, Manila, Philippines

    Ma. Luisa Enriquez

  5. Research and Biotechnology Division, St. Luke’s Medical Center, 279 E. Rodriguez Sr. Avenue, Quezon City, Metro Manila, Philippines

    Ma. Luisa Enriquez

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  1. School of Mathematical Sciences, Universiti Sains Malaysia, Penang, Malaysia

    Mohd Hafiz Mohd

  2. School of Mathematical Sciences, Universiti Sains Malaysia, Penang, Malaysia

    Md Yushalify Misro

  3. School of Mathematical Sciences, Universiti Sains Malaysia, Penang, Malaysia

    Syakila Ahmad

  4. Department of Science and Technology, Thuyloi University, Hanoi, Vietnam

    Doanh Nguyen Ngoc

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Lao, A. et al. (2021). Cytotoxic Activity of Raphanus sativus Linn. on Selected Cancer Cell Lines and Mechanistic Pathways Predicted Through Mathematical Modeling. In: Mohd, M.H., Misro, M.Y., Ahmad, S., Nguyen Ngoc, D. (eds) Modelling, Simulation and Applications of Complex Systems. CoSMoS 2019. Springer Proceedings in Mathematics & Statistics, vol 359. Springer, Singapore. https://doi.org/10.1007/978-981-16-2629-6_9

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