Special Issue "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: 25 August 2022 | Viewed by 17021

Special Issue Editor

Prof. Dr. Bonglee Kim
E-Mail Website
Guest Editor
1. Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, Korea
2. Department of Cancer Preventive Material Development, Kyung Hee University, Seoul, Korea
Interests: oncology; epigenetics; miRNA; natural products; cancer; antioxidants; apoptosis
Special Issues, Collections and Topics in MDPI journals

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 (12 papers)

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Research

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Article
Cytotoxic and Apoptotic Effect of Rubus chingii Leaf Extract against Non-Small Cell Lung Carcinoma A549 Cells
Processes 2022, 10(8), 1537; https://doi.org/10.3390/pr10081537 - 05 Aug 2022
Viewed by 185
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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Article
Comprehensive Analysis of Mutation-Based and Expressed Genes-Based Pathways in Head and Neck Squamous Cell Carcinoma
Processes 2021, 9(5), 792; https://doi.org/10.3390/pr9050792 - 30 Apr 2021
Cited by 1 | Viewed by 743
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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Article
α-Mangostin Synergizes the Antineoplastic Effects of 5-Fluorouracil Allowing a Significant Dose Reduction in Breast Cancer Cells
Processes 2021, 9(3), 458; https://doi.org/10.3390/pr9030458 - 03 Mar 2021
Cited by 2 | Viewed by 862
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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Article
The Effects of Lung-Moistening Herbal Medicines on Bleomycin-Induced Pulmonary Fibrosis Mouse Model
Processes 2020, 8(1), 102; https://doi.org/10.3390/pr8010102 - 12 Jan 2020
Cited by 3 | Viewed by 1822
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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Article
Baicalein-Enriched Fraction Extracted from Oroxylum indicum (L.) Benth. ex Kurz Leaves Exerts Antioxidant and Inhibitory Effects Against Glioblastoma Multiforme
Processes 2019, 7(12), 963; https://doi.org/10.3390/pr7120963 - 16 Dec 2019
Cited by 5 | Viewed by 1332
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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Review
Genistein, a Potential Phytochemical against Breast Cancer Treatment-Insight into the Molecular Mechanisms
Processes 2022, 10(2), 415; https://doi.org/10.3390/pr10020415 - 21 Feb 2022
Cited by 6 | Viewed by 743
Abstract
Breast cancer (BC) is one of the most common malignancies in women. Although widespread successful synthetic drugs are available, natural compounds can also be considered as significant anticancer agents for treating BC. Some natural compounds have similar effects as synthetic drugs with fewer [...] Read more.
Breast cancer (BC) is one of the most common malignancies in women. Although widespread successful synthetic drugs are available, natural compounds can also be considered as significant anticancer agents for treating BC. Some natural compounds have similar effects as synthetic drugs with fewer side effects on normal cells. Therefore, we aimed to unravel and analyze several molecular mechanisms of genistein (GNT) against BC. GNT is a type of dietary phytoestrogen included in the flavonoid group with a similar structure to estrogen that might provide a strong alternative and complementary medicine to existing chemotherapeutic drugs. Previous research reported that GNT could target the estrogen receptor (ER) human epidermal growth factor receptor-2 (HER2) and several signaling molecules against multiple BC cell lines and sensitize cancer cell lines to this compound when used at an optimal inhibitory concentration. More specifically, GNT mediates the anticancer mechanism through apoptosis induction, arresting the cell cycle, inhibiting angiogenesis and metastasis, mammosphere formation, and targeting and suppressing tumor growth factors. Furthermore, it acts via upregulating tumor suppressor genes and downregulating oncogenes in vitro and animal model studies. In addition, this phytochemical synergistically reverses the resistance mechanism of standard chemotherapeutic drugs, increasing their efficacy against BC. Overall, in this review, we discuss several molecular interactions of GNT with numerous cellular targets in the BC model and show its anticancer activities alone and synergistically. We conclude that GNT can have favorable therapeutic advantages when standard drugs are not available in the pharma markets. Full article
(This article belongs to the Special Issue Cancer Systems Biology and Natural Products)
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Review
A Comprehensive Review of Recent Advancements in Cancer Immunotherapy and Generation of CAR T Cell by CRISPR-Cas9
Processes 2022, 10(1), 16; https://doi.org/10.3390/pr10010016 - 23 Dec 2021
Cited by 1 | Viewed by 1568
Abstract
The mechanisms involved in immune responses to cancer have been extensively studied for several decades, and considerable attention has been paid to harnessing the immune system’s therapeutic potential. Cancer immunotherapy has established itself as a promising new treatment option for a variety of [...] Read more.
The mechanisms involved in immune responses to cancer have been extensively studied for several decades, and considerable attention has been paid to harnessing the immune system’s therapeutic potential. Cancer immunotherapy has established itself as a promising new treatment option for a variety of cancer types. Various strategies including cancer vaccines, monoclonal antibodies (mAbs), adoptive T-cell cancer therapy and CAR T-cell therapy have gained prominence through immunotherapy. However, the full potential of cancer immunotherapy remains to be accomplished. In spite of having startling aspects, cancer immunotherapies have some difficulties including the inability to effectively target cancer antigens and the abnormalities in patients’ responses. With the advancement in technology, this system has changed the genome-based immunotherapy process in the human body including the generation of engineered T cells. Due to its high specificity, CRISPR-Cas9 has become a simple and flexible genome editing tool to target nearly any genomic locus. Recently, the CD19-mediated CAR T-cell (chimeric antigen receptor T cell) therapy has opened a new avenue for the treatment of human cancer, though low efficiency is a major drawback of this process. Thus, increasing the efficiency of the CAR T cell (engineered T cells that induce the chimeric antigen receptor) by using CRISPR-Cas9 technology could be a better weapon to fight against cancer. In this review, we have broadly focused on recent immunotherapeutic techniques against cancer and the use of CRISPR-Cas9 technology for the modification of the T cell, which can specifically recognize cancer cells and be used as immune-therapeutics against cancer. Full article
(This article belongs to the Special Issue Cancer Systems Biology and Natural Products)
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Review
Exhaustive Plant Profile of “Dimocarpus longan Lour” with Significant Phytomedicinal Properties: A Literature Based-Review
Processes 2021, 9(10), 1803; https://doi.org/10.3390/pr9101803 - 11 Oct 2021
Cited by 6 | Viewed by 1279
Abstract
Background: “Dimocarpus longan Lour” is a tropical and subtropical evergreen tree species mainly found in China, India, and Thailand; this plant, found naturally in Bangladesh, even locally, is used as “kaviraj” medication for treating different diseases, such as gastrointestinal disorders, wounds, fever, [...] Read more.
Background: “Dimocarpus longan Lour” is a tropical and subtropical evergreen tree species mainly found in China, India, and Thailand; this plant, found naturally in Bangladesh, even locally, is used as “kaviraj” medication for treating different diseases, such as gastrointestinal disorders, wounds, fever, snake bites, menstrual problem, chickenpox, bone fractures, neurological disorders, and reproductive health. Different parts of this plant, especially juice pulp, pericarp, seeds, leaves, and flowers, contain a diverse group of botanical phytocompounds, and nutrient components which are directly related to alleviating numerous diseases. This literature-based review provides the most up-to-date data on the ethnomedicinal usages, phytochemical profiling, and bio-pharmacological effects of D. longan Lour based on published scientific articles. Methodology: A literature-based review was conducted by collecting information from various published papers in reputable journals and cited organizations. ChemDraw, a commercial software package, used to draw the chemical structure of the phytochemicals. Results: Various phytochemicals such as flavonoids, tannins, and polyphenols were collected from the various sections of the plant, and other compounds like vitamins and minerals were also obtained from this plant. As a treating agent, this plant displayed many biologicals activities, such as anti-proliferative, antioxidant, anti-cancer, anti-tyrosinase, radical scavenging activity, anti-inflammatory activity, anti-microbial, activation of osteoblast differentiation, anti-fungal, immunomodulatory, probiotic, anti-aging, anti-diabetic, obesity, neurological issues, and suppressive effect on macrophages cells. Different plant parts have displayed better activity in different disease conditions. Still, the compounds, such as gallic acid, ellagic acid, corilagin acid, quercetin, 4-O-methyl gallic acid, and (-)-epicatechin showed better activity in the biological system. Gallic acid, corilagin, and ellagic acid strongly exhibited anti-cancer activity in the HepG2, A549, and SGC 7901 cancer cell lines. Additionally, 4-O-methyl gallic acid and (-)-epicatechin have displayed outstanding antioxidant activity as well as anti-cancer activity. Conclusion: This plant species can be considered an alternative source of medication for some diseases as it contains a potential group of chemical constituents. Full article
(This article belongs to the Special Issue Cancer Systems Biology and Natural Products)
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Review
Anti-Cancer Effect of Panax Ginseng and Its Metabolites: From Traditional Medicine to Modern Drug Discovery
Processes 2021, 9(8), 1344; https://doi.org/10.3390/pr9081344 - 30 Jul 2021
Viewed by 1046
Abstract
Cancer incidence and mortality rate are growing worldwide. The effectiveness of cancer therapy depends on the degree of cancer development. Anticancer prevention, screening tests, detection of precancerous conditions or cancers at an early stage of development help to prevent the development of cancer, [...] Read more.
Cancer incidence and mortality rate are growing worldwide. The effectiveness of cancer therapy depends on the degree of cancer development. Anticancer prevention, screening tests, detection of precancerous conditions or cancers at an early stage of development help to prevent the development of cancer, and in the event of cancer development, they provide the best chance for a full recovery. However, in most cases of advanced cancer, there is no method that can fully cure this disease. Recently, natural products have gained more attention in cancer therapy. Panax ginseng (PG), one of the most popular natural products, is reported to have a wide range of pharmacological activities in cancer. Therefore, the anti-cancer effects and mechanisms of PG and its metabolites (compound K, Ginsenoside Rh1, Rh2, Rh3 and F1) in five major cancers (lung cancer, breast cancer, colon cancer, prostate cancer and stomach cancer) are reviewed in this study. It is confirmed that PG and its metabolites regulated apoptosis, epithelial mesenchymal transition (EMT), angiogenesis, cell cycle arrest and multidrug resistance (MDR) in vitro and in vivo cancer models. In particular, ginsenoside Rh2 showed anticancer effects in all five major cancers. This review could improve the understanding of anticancer mechanisms of PG and its metabolites against major five cancers. Further clinical studies are needed for development anti-cancer drugs using PG and its metabolites. Full article
(This article belongs to the Special Issue Cancer Systems Biology and Natural Products)
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Review
Review of Natural Compounds for the Management and Prevention of Lymphoma
Processes 2020, 8(9), 1164; https://doi.org/10.3390/pr8091164 - 16 Sep 2020
Viewed by 1141
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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Review
Effect of Oxaliplatin on Voltage-Gated Sodium Channels in Peripheral Neuropathic Pain
Processes 2020, 8(6), 680; https://doi.org/10.3390/pr8060680 - 09 Jun 2020
Cited by 5 | Viewed by 1055
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)
Review
Microbial Natural Products in Drug Discovery
Processes 2020, 8(4), 470; https://doi.org/10.3390/pr8040470 - 16 Apr 2020
Cited by 31 | Viewed by 4035
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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