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Phytochemical-Based Strategies and Approaches of Targeting STAT3 for Regulating Lipid...
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Phytochemical-Based Strategies and Approaches of Targeting STAT3 for Regulating Lipid Homeostasis in Cancer Microenvironment

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 May 2020) | Viewed by 19599

Special Issue Editor

Prof. Dr. Jae-Young Um

E-Mail Website
Guest Editor
Department of Science in Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea
Interests: cancer; cancer microenvironment; lipid homeostasis; STAT3; phytochemicals

Special Issue Information

Dear Colleagues,

Signal transducers and activators of transcription (STATs) are a family of transcription factors that regulate cell proliferation, apoptosis, inflammation, and angiogenesis. Recent findings suggest that the STAT family, particularly STAT3, plays a critical role in cancer and its microenvironments by affecting lipid homeostasis during initiation and progression of cancer. Therefore, understanding the STAT3-related mechanisms that regulate lipid homeostasis in cancer microenvironment will be fundamental to our understanding of pathological conditions and development of therapeutic approaches of cancer. In this Special Issue of Biomolecules, “Phytochemical-Based Strategies and Approaches of Targeting STAT3 for Regulating Lipid Homeostasis in Cancer Microenvironment”, experts are invited to contribute original research papers or review articles that will provide further insights into phytochemical approaches to improve cancer by regulating lipid homeostasis in cancer microenvironments focusing on the role of STAT3.

Prof. Dr. Jae-Young Um
Guest Editor

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Keywords

  • STAT3
  • cancer
  • cancer microenvironment
  • lipid homeostasis
  • phytochemicals

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Published Papers (4 papers)

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Research

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18 pages, 2762 KiB  
Article
Vanillic Acid Improves Comorbidity of Cancer and Obesity through STAT3 Regulation in High-Fat-Diet-Induced Obese and B16BL6 Melanoma-Injected Mice
by Jinbong Park, Seon Yeon Cho, JongWook Kang, Woo Yong Park, Sujin Lee, Yunu Jung, Min-Woo Kang, Hyun Jeong Kwak and Jae-Young Um
Biomolecules 2020, 10(8), 1098; https://doi.org/10.3390/biom10081098 - 24 Jul 2020
Cited by 18 | Viewed by 3230
Abstract
Obesity is known to be associated with risk and aggressiveness of cancer. Melanoma, the most lethal type of skin cancer, is also closely related to the prevalence of obesity. In this study, we established a cancer–obesity comorbidity (COC) model to investigate the effects [...] Read more.
Obesity is known to be associated with risk and aggressiveness of cancer. Melanoma, the most lethal type of skin cancer, is also closely related to the prevalence of obesity. In this study, we established a cancer–obesity comorbidity (COC) model to investigate the effects of vanillic acid (VA). After a five-week administration with a high-fat diet (HFD) to induce obesity, subcutaneous allograft of B16BL6 cells were followed, and VA was orally administrated for an additional two weeks. VA-fed mice showed significantly decreased body weight and white adipose tissue (WAT) weight, which were due to increased thermogenesis and AMPK activation in WATs. Growth of cancer was also suppressed. Mechanistic studies revealed increased apoptosis and autophagy markers by VA; however, caspase 3 was not involved. Since signal transducer and activator of transcription 3 (STAT3) is suggested as an important pathway linking obesity and cancer, we further investigated to find out if STAT3 phosphorylation was repressed by VA treatment, and this was again confirmed in a COC cell model of adipocyte conditioned medium-treated B16BL6 melanoma cells. Overall, our results show VA induces STAT3-mediated autophagy to inhibit cancer growth and thermogenesis to ameliorate obesity in COC. Based on these findings, we suggest VA as a candidate therapeutic agent for COC treatment. Full article
(This article belongs to the Special Issue Phytochemical-Based Strategies and Approaches of Targeting STAT3 for Regulating Lipid Homeostasis in Cancer Microenvironment)
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22 pages, 6097 KiB  
Article
Significance of STAT3 in Immune Infiltration and Drug Response in Cancer
by Wei Chen, Xiaoshuo Dai, Yihuan Chen, Fang Tian, Yanyan Zhang, Qiushuang Zhang and Jing Lu
Biomolecules 2020, 10(6), 834; https://doi.org/10.3390/biom10060834 - 29 May 2020
Cited by 18 | Viewed by 3977
Abstract
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor and regulates tumorigenesis. However, the functions of STAT3 in immune and drug response in cancer remain elusive. Hence, we aim to reveal the impact of STAT3 in immune infiltration and drug [...] Read more.
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor and regulates tumorigenesis. However, the functions of STAT3 in immune and drug response in cancer remain elusive. Hence, we aim to reveal the impact of STAT3 in immune infiltration and drug response comprehensively by bioinformatics analysis. The expression of STAT3 and its relationship with tumor stage were explored by Tumor Immune Estimation Resource (TIMER), Human Protein Altas (HPA), and UALCAN databases. The correlations between STAT3 and immune infiltration, gene markers of immune cells were analyzed by TIMER. Moreover, the association between STAT3 and drug response was evaluated by the Cancer Cell Line Encyclopedia (CCLE) and Cancer Therapeutics Response Portal (CTRP). The results suggested that the mRNA transcriptional level of STAT3 was lower in tumors than normal tissues and mostly unrelated to tumor stage. Besides, the protein expression of STAT3 decreased in colorectal and renal cancer compared with normal tissues. Importantly, STAT3 was correlated with immune infiltration and particularly regulated tumor-associated macrophage (TAM), M2 macrophage, T-helper 1 (Th1), follicular helper T (Treg), and exhausted T-cells. Remarkably, STAT3 was closely correlated with the response to specified inhibitors and natural compounds in cancer. Furthermore, the association between STAT3 and drug response was highly cell line type dependent. Significantly, the study provides thorough insight that STAT3 is associated with immunosuppression, as well as drug response in clinical treatment. Full article
(This article belongs to the Special Issue Phytochemical-Based Strategies and Approaches of Targeting STAT3 for Regulating Lipid Homeostasis in Cancer Microenvironment)
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15 pages, 3554 KiB  
Article
Attenuation of STAT3 Signaling Cascade by Daidzin Can Enhance the Apoptotic Potential of Bortezomib against Multiple Myeloma
by Min Hee Yang, Sang Hoon Jung, Arunachalam Chinnathambi, Tahani Awad Alahmadi, Sulaiman Ali Alharbi, Gautam Sethi and Kwang Seok Ahn
Biomolecules 2020, 10(1), 23; https://doi.org/10.3390/biom10010023 - 23 Dec 2019
Cited by 34 | Viewed by 6347
Abstract
Daidzin (DDZ) extracted from Pueraria lobate (Fabaceae) is a widely known phytoestrogen. DDZ can display anti-cancer activities against breast and prostate cancers, but its anti-oncogenic actions in multiple myeloma (MM) cells have not been studied. The signal transducer and activator of transcription 3 [...] Read more.
Daidzin (DDZ) extracted from Pueraria lobate (Fabaceae) is a widely known phytoestrogen. DDZ can display anti-cancer activities against breast and prostate cancers, but its anti-oncogenic actions in multiple myeloma (MM) cells have not been studied. The signal transducer and activator of transcription 3 (STAT3) can control key processes including proliferation, differentiation, and survival in MM cells. Here, we noted that DDZ abrogated STAT3 activation (both constitutive as well as inducible) at Tyr705 and Ser727 in MM cells. Additionally, DDZ mitigated the phosphorylation of STAT3 upstream Janus-activated kinases (JAK1/2) and c-Src kinases. Pervanadate (tyrosine phosphatase blocker) exposure altered the DDZ-induced inhibition of STAT3 activation, thus affecting the action of this phytoestrogen on apoptosis. Moreover, DDZ impeded proliferation and augmented the apoptotic effects of bortezomib (Bor) in MM cells. Overall, the data indicate that DDZ may act as a potent suppressor of STAT3 signaling cascade, and the co-treatment of DDZ and Bor could be a promising therapeutic strategy, specifically in MM. Full article
(This article belongs to the Special Issue Phytochemical-Based Strategies and Approaches of Targeting STAT3 for Regulating Lipid Homeostasis in Cancer Microenvironment)
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Review

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22 pages, 7235 KiB  
Review
Phytochemical Targeting of STAT3 Orchestrated Lipid Metabolism in Therapy-Resistant Cancers
by Carmen Tse, Ashleigh Warner, Rufaik Farook and James G Cronin
Biomolecules 2020, 10(8), 1118; https://doi.org/10.3390/biom10081118 - 28 Jul 2020
Cited by 12 | Viewed by 5654
Abstract
Lipids are critical for maintaining homeostasis and cellular metabolism. However, the dysregulation of lipid metabolism contributes to the pathogenesis of chronic inflammatory diseases and is a hallmark of several cancer types. Tumours exist in a microenvironment of poor vascularization-depleted oxygen and restricted nutrients. [...] Read more.
Lipids are critical for maintaining homeostasis and cellular metabolism. However, the dysregulation of lipid metabolism contributes to the pathogenesis of chronic inflammatory diseases and is a hallmark of several cancer types. Tumours exist in a microenvironment of poor vascularization-depleted oxygen and restricted nutrients. Under these conditions, tumours have been shown to increasingly depend on the metabolism of fatty acids for sustained proliferation and survival. Signal transducer and activator of transcription 3 (STAT3) plays a key role in cellular processes such as cell growth, apoptosis and lipid metabolism. Aberrant STAT3 activity, as seen in several cancer types, is associated with tumour progression and malignancy, in addition to propagating crosstalk between tumour cells and the microenvironment. Furthermore, STAT3-regulated lipid metabolism is critical for cancer stem cell self-renewal and therapy resistance. Plant-derived compounds known as phytochemicals are a potential source for novel cancer therapeutic drugs. Dietary phytochemicals are known to modulate key cellular signalling pathways involved in lipid homeostasis and metabolism, including the STAT3 signalling pathways. Targeting STAT3 orchestrated lipid metabolism has shown therapeutic promise in human cancer models. In this review, we summarize the antitumour activity of phytochemicals with an emphasis placed on their effect on STAT3-regulated lipid metabolism and their role in abrogating therapy resistance. Full article
(This article belongs to the Special Issue Phytochemical-Based Strategies and Approaches of Targeting STAT3 for Regulating Lipid Homeostasis in Cancer Microenvironment)
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