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2021 | OriginalPaper | Chapter

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

Authors : Angelyn Lao, Jan Marie Claire Edra, Kathleen Dane Talag, Daisylyn Senna Tan, Glenn Oyong, Marissa Noel, Ma. Luisa Enriquez, Maria Carmen Tan

Published in: Modelling, Simulation and Applications of Complex Systems

Publisher: Springer Singapore

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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Title: Cytotoxic Activity of Raphanus sativus Linn. on Selected Cancer Cell Lines and Mechanistic Pathways Predicted Through Mathematical Modeling
Authors: Angelyn Lao
Jan Marie Claire Edra
Kathleen Dane Talag
Daisylyn Senna Tan
Glenn Oyong
Marissa Noel
Ma. Luisa Enriquez
Maria Carmen Tan
Publisher: Springer Singapore
Book: Modelling, Simulation and Applications of Complex Systems
Print ISBN: 978-981-16-2628-9

Electronic ISBN: 978-981-16-2629-6

Copyright Year: 2021
DOI: https://doi.org/10.1007/978-981-16-2629-6_9

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