Cancer Systems Biology and Natural Products

A special issue of Processes (ISSN 2227-9717). This special issue belongs to the section "Biological Processes and Systems".

Deadline for manuscript submissions: closed (25 August 2022) | Viewed by 35814

Special Issue Editor

Special Issue Information

Dear Colleagues,

Cancer systems biology has emerged because cancer is a complicated disease system involving complex molecular and genetic events. Recent developments of technologies in genomics and proteomics have provided methods and information to researchers with a holistic view of cancer and the local microenvironment, while traditional cancer research only focuses on single mutations or alterations. Natural products include naturally-produced chemical compounds or substances from any living organism. The benefits of natural products have been reported in the form of studies of traditional medicine for the treatment of several human diseases, including Alzheimer’s disease, inflammatory diseases, influenza disease, and cancer. Multi-target drugs based on natural products have been discovered, such as curcumin, resveratrol, etc., and approved by the U.S. Food and Drug Administration. Natural products could be primary sources of cancer drug discovery in terms of cancer systems biology.

We propose a Special Issue on “Cancer Systems Biology and Natural Products” to publish high-quality work focusing on novel and recent advances in natural products in cancer system biology applications, including traditional medicine, biomaterials, etc. The topics of interest include, but are not limited to:

  • Cancer systems biology
  • Cancer microenvironment
  • Natural products for cancer therapy
  • Traditional medicine for cancer therapy

Prof. Dr. Bonglee Kim
Guest Editor

Manuscript Submission Information

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Keywords

  • Cancer systems biology
  • Cancer microenvironment
  • Natural products
  • Traditional medicine
  • Epigenetics

Published Papers (8 papers)

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Research

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14 pages, 2382 KiB  
Article
Cytotoxic and Apoptotic Effect of Rubus chingii Leaf Extract against Non-Small Cell Lung Carcinoma A549 Cells
by El-Sayed Khafagy, Ahmed Al Saqr, Hadil Faris Alotaibi and Amr Selim Abu Lila
Processes 2022, 10(8), 1537; https://doi.org/10.3390/pr10081537 - 05 Aug 2022
Cited by 3 | Viewed by 1318
Abstract
Rubus chingii is a traditional Chinese medicinal herbal that has been used since ancient times for its great dietary and medicinal values. Recent reports have underscored the promising cytotoxic effect of R. chingii extracts against a wide variety of cancer cells. Therefore, in [...] Read more.
Rubus chingii is a traditional Chinese medicinal herbal that has been used since ancient times for its great dietary and medicinal values. Recent reports have underscored the promising cytotoxic effect of R. chingii extracts against a wide variety of cancer cells. Therefore, in the current study, we aim to explore the anticancer potential of the Rubus chingii ethanolic leaf extract (RcL-EtOH) against non-small cell lung cancer A549 cells. RcL-EtOH efficiently exerted a cytotoxic effect against A549 cells in a dose dependent manner, whilst, it exhibited non-significant toxic effects on normal murine macrophage cells, signifying its safety against normal cells. The reduced viability of A549 cells was reaffirmed by the acridine orange/ethidium bromide double staining, which confirmed the induction of apoptosis in RcL-EtOH-treated A549 cells. In addition, RcL-EtOH instigated the dissipation of mitochondrial membrane potential (ΔΨm) with mutual escalation in ROS generation in a dose-dependent manner. Furthermore, RcL-EtOH increased caspase-3, caspase-9 levels in A549 cells post-exposure to RcL-EtOH, which was concomitantly followed by altered mRNA expression of apoptotic (anti-apoptotic: Bcl-2, BclXL; pro-apoptotic: Bax, Bad). To sum up, the RcL-EtOH-instigated apoptotic cell death within A549 cells was assumed to be accomplished via targeting mitochondria, triggering increased ROS generation, with subsequent activation of caspase cascade and altering the expression of gene regulating apoptosis. Collectively, RcL-EtOH might represent a plausible therapeutic option for the management of lung cancer. Full article
(This article belongs to the Special Issue Cancer Systems Biology and Natural Products)
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13 pages, 1169 KiB  
Article
Comprehensive Analysis of Mutation-Based and Expressed Genes-Based Pathways in Head and Neck Squamous Cell Carcinoma
by Bhumsuk Keam, Jin-Young Park, Jin-Pyo Kim, Gun-Do Kim, Yun-Suk Yu, Sang-Hee Cho, Sangwoo Kim, Hee-Kyung Ahn, Sang-Hoon Chun, Jung-Hye Kwon, Tak Yun, Ji-Won Kim, Ji-Eun Kim, Myung-Ju Ahn, Joo-Hang Kim and Hwan-Jung Yun
Processes 2021, 9(5), 792; https://doi.org/10.3390/pr9050792 - 30 Apr 2021
Cited by 1 | Viewed by 1721
Abstract
Over- or under-expression of mRNA results from genetic alterations. Comprehensive pathway analyses based on mRNA expression are as important as single gene level mutations. This study aimed to compare the mutation- and mRNA expression-based signaling pathways in head and neck squamous cell carcinoma [...] Read more.
Over- or under-expression of mRNA results from genetic alterations. Comprehensive pathway analyses based on mRNA expression are as important as single gene level mutations. This study aimed to compare the mutation- and mRNA expression-based signaling pathways in head and neck squamous cell carcinoma (HNSCC) and to match these with potential drug or druggable pathways. Altogether, 93 recurrent/metastatic HNSCC patients were enrolled. We performed targeted gene sequencing using Illumina HiSeq-2500 for NGS, and nanostring nCounter® for mRNA expression; mRNA expression was classified into over- or under-expression groups based on the expression. We investigated mutational and nanostring data using the CBSJukebox® system, which is a big-data driven platform to analyze druggable pathways, genes, and protein-protein interaction. We calculated a Treatment Benefit Prediction Score (TBPS) to identify suitable drugs. By mapping the high score interaction genes to identify druggable pathways, we found highly related signaling pathways with mutations. Based on the mRNA expression and interaction gene scoring model, several pathways were found to be associated with over- and under-expression. Mutation-based pathways were associated with mRNA under-expressed genes-based pathways. These results suggest that HNSCCs are mainly caused by the loss-of-function mutations. TBPS found several matching drugs such as immune checkpoint inhibitors, EGFR inhibitors, and FGFR inhibitors. Full article
(This article belongs to the Special Issue Cancer Systems Biology and Natural Products)
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12 pages, 1685 KiB  
Article
α-Mangostin Synergizes the Antineoplastic Effects of 5-Fluorouracil Allowing a Significant Dose Reduction in Breast Cancer Cells
by Galia Lara-Sotelo, Lorenza Díaz, Rocío García-Becerra, Euclides Avila, Heriberto Prado-Garcia, Gabriela Morales-Guadarrama, María de Jesús Ibarra-Sánchez, José Esparza-López, Fernando Larrea and Janice García-Quiroz
Processes 2021, 9(3), 458; https://doi.org/10.3390/pr9030458 - 03 Mar 2021
Cited by 5 | Viewed by 2431
Abstract
Breast cancer is the most common neoplasm and the leading cause of cancer death in women worldwide. Although 5-fluorouracil is a conventional chemotherapeutic agent for breast cancer treatment, its use may result in severe side effects. Thus, there is widespread interest in lowering [...] Read more.
Breast cancer is the most common neoplasm and the leading cause of cancer death in women worldwide. Although 5-fluorouracil is a conventional chemotherapeutic agent for breast cancer treatment, its use may result in severe side effects. Thus, there is widespread interest in lowering 5-fluorouracil drawbacks, without affecting its therapeutic efficacy by the concomitant use with natural products. Herein, we aimed at evaluating whether α-mangostin, a natural antineoplastic compound, could increase the anticancer effect of 5-fluorouracil in different breast cancer cell lines, allowing for dose reduction. Cell proliferation was evaluated by sulforhodamine-B assays, inhibitory concentrations and potency were calculated by dose-response curves, followed by analysis of their pharmacological interaction by the combination-index method and dose-reduction index. Cell cycle distribution was evaluated by flow cytometry. Each compound inhibited cell proliferation in a dose-dependent manner, the triple negative breast cancer cells being the most sensitive. When 5-fluorouracil and α-mangostin were used concomitantly, synergistic antiproliferative effect was observed. The calculated dose-reduction index suggested that this combination exhibits therapeutic potential for reducing 5-fluorouracil dosage in breast cancer. Mechanistically, the cotreatment induced cell death in a greater extent than each drug alone. Therefore, α-mangostin could be used as a potent co-adjuvant for 5-fluorouracil in breast cancer. Full article
(This article belongs to the Special Issue Cancer Systems Biology and Natural Products)
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7 pages, 1178 KiB  
Article
The Effects of Lung-Moistening Herbal Medicines on Bleomycin-Induced Pulmonary Fibrosis Mouse Model
by Junmo Ahn, Hyejin Joo, Jihye Park, Jae-Woo Park, Kwan-Il Kim, Hee-Jae Jung, Youngmin Bu and Beom-Joon Lee
Processes 2020, 8(1), 102; https://doi.org/10.3390/pr8010102 - 12 Jan 2020
Cited by 5 | Viewed by 4168
Abstract
In traditional medicine, lung-moistening herbal medicines (LMHM) are regarded as a major option for treating symptoms of pulmonary fibrosis (PF) including dry cough and dyspnea. As PF agents are being applied to the development of lung cancer agents, PF and lung cancer are [...] Read more.
In traditional medicine, lung-moistening herbal medicines (LMHM) are regarded as a major option for treating symptoms of pulmonary fibrosis (PF) including dry cough and dyspnea. As PF agents are being applied to the development of lung cancer agents, PF and lung cancer are reported to have high pathological and pharmacological relationships. This study was proposed to identify candidates for the treatment of PF via investigating the effect of LMHM on PF mouse model. PF was induced by intratracheal instillation of bleomycin. Six water extracts of LMHM such as Farfarae Flos (FAF), Trichosanthis Semen (TRS), Lilii Bulbus (LIB), Adenophorae Radix (ADR), Asteris Radix (ASR), and Scrophulariae Radix (SCR) were prepared and administered (300 mg/kg) orally for 10 days after induction. The changes in body weight, histopathology, and immune cell of bronchoalveolar lavage fluid (BALF) were investigated. Among those, LIB and ADR significantly decreased the deposition of collagen and septal thickness of alveolar and terminal bronchiole. Moreover, SCR, TRS, LIB, and ADR decreased total cells, macrophages, and lymphocytes in BALF. Taken together, ADR and LIB could be the candidates to reduce PF. Further studies on their effects at different doses and analysis of their underlying molecular mechanisms are needed. Full article
(This article belongs to the Special Issue Cancer Systems Biology and Natural Products)
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16 pages, 4321 KiB  
Article
Baicalein-Enriched Fraction Extracted from Oroxylum indicum (L.) Benth. ex Kurz Leaves Exerts Antioxidant and Inhibitory Effects Against Glioblastoma Multiforme
by In Nee Kang, Nik Nur Hakimah Nik Salleh, Wan Jie Chung, Chong Yew Lee and Suat Cheng Tan
Processes 2019, 7(12), 963; https://doi.org/10.3390/pr7120963 - 16 Dec 2019
Cited by 10 | Viewed by 3880
Abstract
Glioblastoma multiforme (GBM) is the most malignant subtype of primary brain cancer. To date, standard clinical treatment for GBM is limited in effectiveness and could impose additional side effects. Recently, numerous bioactive compounds isolated from natural plants appear to have beneficial anti-cancer properties. [...] Read more.
Glioblastoma multiforme (GBM) is the most malignant subtype of primary brain cancer. To date, standard clinical treatment for GBM is limited in effectiveness and could impose additional side effects. Recently, numerous bioactive compounds isolated from natural plants appear to have beneficial anti-cancer properties. Here, the GBM inhibitory effect of baicalein, a bioactive flavonoid extracted from Oroxylum indicum (L.) Benth. ex Kurz, was evaluated. Firstly, three solvents were used to extract the baicalein. We found that the binary extraction system, using a combination of petroleum ether and methanol (PM), yielded the highest amount of baicalein (15%) compared to the mono extraction system using methanol (13%) or aqueous (0.04%) only. In order to further enhance the baicalein yield in PM crude extract, it was subjected to an enrichment fractionation procedure, which successfully increased the baicalein by nearly two-fold from the initial crude extract (15%) to the enriched fraction 5 (F5) (29%). The enriched F5 not only showed significantly higher (~2.5-fold) antioxidant properties as compared to the crude extract, it was also found to significantly suppress GBM cell proliferation ~2.5-fold better than the crude extract. In conclusion, this study successfully optimized an extraction procedure for increased yield of baicalein metabolite from O. indicum leaves and enhanced its therapeutic potential for GBM treatment. Full article
(This article belongs to the Special Issue Cancer Systems Biology and Natural Products)
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Review

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25 pages, 1360 KiB  
Review
Review of Natural Compounds for the Management and Prevention of Lymphoma
by Yongmin Cho, Moon Nyeo Park, Seungjin Noh, Seog Young Kang and Bonglee Kim
Processes 2020, 8(9), 1164; https://doi.org/10.3390/pr8091164 - 16 Sep 2020
Cited by 2 | Viewed by 2946
Abstract
Lymphoma is a type of blood cancer that can be categorized into two types-Hodgkin lymphoma (HL) and Non-Hodgkin lymphoma (NHL). A total of 509,590 and 79,990 cases of NHL and HL were newly diagnosed in 2018, respectively. Although conventional therapy has stridden forward [...] Read more.
Lymphoma is a type of blood cancer that can be categorized into two types-Hodgkin lymphoma (HL) and Non-Hodgkin lymphoma (NHL). A total of 509,590 and 79,990 cases of NHL and HL were newly diagnosed in 2018, respectively. Although conventional therapy has stridden forward over recent decades, its adverse effects are still a hurdle to be solved. Thus, to help researchers develop better lymphoma treatment, this study aims to review the systematic anticancer data for natural products and their compounds. A variety of natural products showed anticancerous effects on lymphoma by regulation of intracellular mechanisms including apoptosis as well as cell cycle arrest. As these results shed light on the potential to substitute conventional therapy with natural products, it may become a promising strategy for lymphoma treatment in the near future. Full article
(This article belongs to the Special Issue Cancer Systems Biology and Natural Products)
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13 pages, 229 KiB  
Review
Effect of Oxaliplatin on Voltage-Gated Sodium Channels in Peripheral Neuropathic Pain
by Woojin Kim
Processes 2020, 8(6), 680; https://doi.org/10.3390/pr8060680 - 09 Jun 2020
Cited by 6 | Viewed by 2583
Abstract
Oxaliplatin is a chemotherapeutic drug widely used to treat various types of tumors. However, it can induce a serious peripheral neuropathy characterized by cold and mechanical allodynia that can even disrupt the treatment schedule. Since the approval of the agent, many laboratories, including [...] Read more.
Oxaliplatin is a chemotherapeutic drug widely used to treat various types of tumors. However, it can induce a serious peripheral neuropathy characterized by cold and mechanical allodynia that can even disrupt the treatment schedule. Since the approval of the agent, many laboratories, including ours, have focused their research on finding a drug or method to decrease this side effect. However, to date no drug that can effectively reduce the pain without causing any adverse events has been developed, and the mechanism of the action of oxaliplatin is not clearly understood. On the dorsal root ganglia (DRG) sensory neurons, oxaliplatin is reported to modify their functions, such as the propagation of the action potential and induction of neuropathic pain. Voltage-gated sodium channels in the DRG neurons are important, as they play a major role in the excitability of the cell by initiating the action potential. Thus, in this small review, eight studies that investigated the effect of oxaliplatin on sodium channels of peripheral neurons have been included. Its effects on the duration of the action potential, peak of the sodium current, voltage–response relationship, inactivation current, and sensitivity to tetrodotoxin (TTX) are discussed. Full article
(This article belongs to the Special Issue Cancer Systems Biology and Natural Products)
19 pages, 2422 KiB  
Review
Microbial Natural Products in Drug Discovery
by Ahmed S. Abdel-Razek, Mehrez E. El-Naggar, Ahmed Allam, Osama M. Morsy and Sarah I. Othman
Processes 2020, 8(4), 470; https://doi.org/10.3390/pr8040470 - 16 Apr 2020
Cited by 90 | Viewed by 15099
Abstract
Over a long period of time, humans have explored many natural resources looking for remedies of various ailments. Traditional medicines have played an intrinsic role in human life for thousands of years, with people depending on medicinal plants and their products as dietary [...] Read more.
Over a long period of time, humans have explored many natural resources looking for remedies of various ailments. Traditional medicines have played an intrinsic role in human life for thousands of years, with people depending on medicinal plants and their products as dietary supplements as well as using them therapeutically for treatment of chronic disorders, such as cancer, malaria, diabetes, arthritis, inflammation, and liver and cardiac disorders. However, plant resources are not sufficient for treatment of recently emerging diseases. In addition, the seasonal availability and other political factors put constrains on some rare plant species. The actual breakthrough in drug discovery came concurrently with the discovery of penicillin from Penicillium notatum in 1929. This discovery dramatically changed the research of natural products and positioned microbial natural products as one of the most important clues in drug discovery due to availability, variability, great biodiversity, unique structures, and the bioactivities produced. The number of commercially available therapeutically active compounds from microbial sources to date exceeds those discovered from other sources. In this review, we introduce a short history of microbial drug discovery as well as certain features and recent research approaches, specifying the microbial origin, their featured molecules, and the diversity of the producing species. Moreover, we discuss some bioactivities as well as new approaches and trends in research in this field. Full article
(This article belongs to the Special Issue Cancer Systems Biology and Natural Products)
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