Isoliquiritigenin (2',4',4-trihydroxychalcone, ISL), one of the most important bioactive compounds with a chalcone structure, is derived from licorice root. Licorice is commonly known as Glycyrrhiza, including Glycyrrhiza uralensis, Glycyrrhiza radix, and Glycyrrhiza glabra, which are generally available in common foods and Chinese herbal medicines based on a wide variety of biological functions and pharmacological effects, and its derivative (ISL) is utilized as a food additive and adjunct disease treatment. In this review, we summarized the progress over the last 10 years in the targeted pathways and molecular mechanisms of ISL that are involved in the regulation of the onset and progression of different types of cancers.

https://www.mdpi.com/2072-6694/13/1/115/pdf

Perspectives on the Role of Isoliquiritigenin in Cancer.

Simple Summary Negative emotions (NEs) and their impacts have greatly influenced the incidence and risk of breast cancer (BC). The present study aims to provide an association between NEs and the incidence of BC with possible risk factors. A total of 9343 studies were screened; nine studies met all inclusion criteria that were considered for the meta-analysis. Observational studies were included with relative risks (RR) and corresponding 95% confidence intervals (CI). We analyzed data from 129,621 women diagnosed with NEs of which 2080 women were diagnosed with BC and their follow-up year ranges were from 4–24 years. NEs were significantly associated with a higher incidence of BC with other high-risk factors including, geographical distribution, emotion types, standard diagnosis of NEs, and follow-up duration. This study suggests that NEs significantly increase the risk for the incidence of BC, which can be supportive of the prognosis of the disease. Abstract Breast cancer (BC) is one of the common malignant tumors in women and affects 1.6 million new cases globally each year. Investigators have recently found that negative emotions (NEs) and their impacts have greatly influenced the incidence and risk of BC. The present study aims to provide an association between NEs and the incidence of BC with possible risk factors. A total of 9343 studies were screened; nine studies met all inclusion criteria that were considered for the meta-analysis. The qualitative studies were measured by the Newcastle-Ottawa Scale; the observational studies were included with relative risks (RR) and corresponding 95% confidence intervals (CI). Besides the NEs and BC, the possible risk factors were evaluated. We analyzed data from 129,621 women diagnosed with NEs of which 2080 women were diagnosed with BC and their follow-up year ranges were from 4–24 years. NEs were significantly (p < 0.0001) associated with a higher incidence of BC with RR = 1.59, 95% CI:1.15–2.19, with other high-risk factors including, geographical distribution, emotion types, standard diagnosis of NEs, and follow-up duration. This study suggests that NEs significantly increase the risk for the incidence of BC, which can be supportive of the prognosis of the disease.

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Prognostic Value of Negative Emotions on the Incidence of Breast Cancer: A Systematic Review and Meta-Analysis of 129,621 Patients with Breast Cancer

Nanocarriers based novel and effective drug delivery system.

Receptors are macromolecules that transmit information regulating cell proliferation, differentiation, migration and apoptosis, play key roles in oncogenic processes and correlate with the prognoses of cancer patients. Thus, targeting receptors to constrain cancer development and progression has gained widespread interest. Small molecule compounds of natural origin have been widely used as drugs or adjuvant chemotherapeutic agents in cancer therapies due to their activities of selectively killing cancer cells, alleviating drug resistance and mitigating side effects. Meanwhile, many natural compounds, including those targeting receptors, are still under laboratory investigation for their anti-cancer activities and mechanisms. In this review, we classify the receptors by their structures and functions, illustrate the natural compounds targeting these receptors and discuss the mechanisms of their anti-cancer activities. We aim to provide primary knowledge of mechanistic regulation and clinical applications of cancer therapies through targeting deregulated receptors.

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Small Molecule Compounds of Natural Origin Target Cellular Receptors to Inhibit Cancer Development and Progression

FMS-like tyrosine kinase 3 (FLT3) is mutated in approximately 30% of acute myeloid leukemia (AML) patients. The presence of FLT3-ITD (internal tandem duplication, 20-25%) mutation and, to a lesser extent, FLT3-TKD (tyrosine kinase domain, 5-10%) mutation is associated with poorer diagnosis and therapy response since the leukemic cells become hyperproliferative and resistant to apoptosis after continuous activation of FLT3 signaling. Targeting FLT3 has been the focus of many pre-clinical and clinical studies. Hence, many small-molecule FLT3 inhibitors (FLT3is) have been developed, some of which are approved such as midostaurin and gilteritinib to be used in different clinical settings, either in combination with chemotherapy or alone. However, many questions regarding the best treatment strategy remain to be answered. On the other hand, various FLT3-dependent and -independent resistance mechanisms could be evolved during FLT3i therapy which limit their clinical impact. Therefore, identifying molecular mechanisms of resistance and developing novel strategies to overcome this obstacle is a current interest in the field. In this review, recent studies of approved FLT3i and knowledge about major resistance mechanisms of clinically approved FLT3i's will be discussed together with novel treatment approaches such as designing novel FLT3i and dual FLT3i and combination strategies including approved FLT3i plus small-molecule agents targeting altered molecules in the resistant cells to abrogate resistance. Moreover, how to choose an appropriate FLT3i for the patients will be summarized based on what is currently known from available clinical data. In addition, strategies beyond FLT3i's including immunotherapeutics, small-molecule FLT3 degraders, and flavonoids will be summarized to highlight potential alternatives in FLT3-mutated AML therapy. 

Therapeutic Targeting of FLT3 in Acute Myeloid Leukemia: Current Status and Novel Approaches

Breast cancer (BC) is the second most common cancer in women globally after lung cancer. Presently, the most important approach for BC treatment consists of surgery, followed by radiotherapy and chemotherapy. The latter therapeutic methods are often unsuccessful in the treatment of BC because of their various side effects and the damage incurred to healthy tissues and organs. Currently, numerous nanoparticles (NPs) have been identified and synthesized to selectively target BC cells without causing any impairments to the adjacent normal tissues or organs. Based on an exploratory study, this comprehensive review aims to provide information on engineered NPs and their payloads as promising tools in the treatment of BC. Therapeutic drugs or natural bioactive compounds generally incorporate engineered NPs of ideal sizes and shapes to enhance their solubility, circulatory half-life, and biodistribution, while reducing their side effects and immunogenicity. Furthermore, ligands such as peptides, antibodies, and nucleic acids on the surface of NPs precisely target BC cells. Studies on the synthesis of engineered NPs and their impact on BC were obtained from PubMed, Science Direct, and Google Scholar. This review provides insights on the importance of engineered NPs and their methodology for validation as a next-generation platform with preventive and therapeutic effects against BC.

Targeting Engineered Nanoparticles for Breast Cancer Therapy

Licorice is a medicinal herb widely used to treat inflammation-related diseases in China. Isoliquiritigenin (ISL) is an important constituent of licorice and possesses multiple bioactivities. In this study, we examined the selective anti-AML (acute myeloid leukemia) property of ISL via targeting FMS-like tyrosine kinase-3 (FLT3), a certified valid target for treating AML. In vitro, ISL potently inhibited FLT3 kinase, with an IC50 value of 115.1 ± 4.2 nM, and selectively inhibited the proliferation of FLT3-internal tandem duplication (FLT3-ITD) or FLT3-ITD/F691L mutant AML cells. Moreover, it showed very weak activity toward other tested cell lines or kinases. Western blot immunoassay revealed that ISL significantly inhibited the activation of FLT3/Erk1/2/signal transducer and activator of transcription 5 (STAT5) signal in AML cells. Meanwhile, a molecular docking study indicated that ISL could stably form aromatic interactions and hydrogen bonds within the kinase domain of FLT3. In vivo, oral administration of ISL significantly inhibited the MV4-11 flank tumor growth and prolonged survival in the bone marrow transplant model via decreasing the expression of Ki67 and inducing apoptosis. Taken together, the present study identified a novel function of ISL as a selective FLT3 inhibitor. ISL could also be a potential natural bioactive compound for treating AML with FLT3-ITD or FLT3-ITD/F691L mutations. Thus, ISL and licorice might possess potential therapeutic effects for treating AML, providing a new strategy for anti-AML.

https://molpharm.aspetjournals.org/content/molpharm/96/5/589.full.pdf

Isoliquiritigenin, an Orally Available Natural FLT3 Inhibitor from Licorice, Exhibits Selective Anti-Acute Myeloid Leukemia Efficacy In Vitro and In Vivo.

Qing-Qing Liu

Papers

Targeting Engineered Nanoparticles for Breast Cancer Therapy

Isoliquiritigenin, an Orally Available Natural FLT3 Inhibitor from Licorice, Exhibits Selective Anti-Acute Myeloid Leukemia Efficacy In Vitro and In Vivo.