Novel natural product therapeutics targeting both inflammation and cancer

Abstract

Inflammation is recently recognized as one of the hallmarks of human cancer. Chronic inflammatory response plays a critical role in cancer development, progression, metastasis, and resistance to chemotherapy. Conversely, the oncogenic aberrations also generate an inflammatory microenvironment, enabling the development and progression of cancer. The molecular mechanisms of action that are responsible for inflammatory cancer and cancer-associated inflammation are not fully understood due to the complex crosstalk between oncogenic and pro-inflammatory genes. However, molecular mediators that regulate both inflammation and cancer, such as NF-κB and STAT have been considered as promising targets for preventing and treating these diseases. Recent works have further demonstrated an important role of oncogenes (e.g., NFAT1, MDM2) and tumor suppressor genes (e.g., p53) in cancer-related inflammation. Natural products that target these molecular mediators have shown anticancer and anti-inflammatory activities in preclinical and clinical studies. Sesquiterpenoids (STs), a class of novel plant-derived secondary metabolites have attracted great interest in recent years because of their diversity in chemical structures and pharmacological activities. At present, we and other investigators have found that dimeric sesquiterpenoids (DSTs) may exert enhanced activity and binding affinity to molecular targets due to the increased number of alkylating centers and improved conformational flexibility and lipophilicity. Here, we focus our discussion on the activities and mechanisms of action of STs and DSTs in treating inflammation and cancer as well as their structure-activity relationships.

Targeting MDM2 for novel molecular therapy: Beyond oncology

“…Other types of MDM2 inhibitors, especially those that directly inhibit MDM2 itself, for example, SP141, JapA, and MA242, should be evaluated for their therapeutic efficacy and safety, as they may provide stronger activity by blocking both the p53‐dependent and p53‐independent functions of MDM2. Further evaluation and development of MDM2 inhibitors for cancer therapy are underway . These studies will provide proof‐of‐principle results to support the therapeutic value of this targeting strategy in drug discovery and may greatly contribute to the development of new therapeutics to treat noncancer diseases.…”

Predictive impact of the inflammation‐based indices in colorectal cancer patients with adjuvant chemotherapy

“…Various studies have indicated that changes of immune cellular components in peripheral venous blood could reflect tumor inflammation status for predicting survival prognosis . There is a growing interpretation of the relationship between inflammation and tumor, resulting in the establishment of novel biomarkers of cancer to evaluate the prognostic significance . It is reported that neutrophils reflect the systematic inflammation status and accelerate the extracellular matrix remodel, which stimulate the tumor cell proliferation, migration, and metastasis through its enzymatic actions, such as the release of reactive oxygen species (ROS), nitric oxide (NO), and proteases .…”

<p>Molecular Mechanisms of Anticancer Activities of Puerarin</p>

“…Recent studies have reported that NPs target both cancer and inflammation. 132 Pue inhibits the tumor volume and its growth in the NSCLC xenograft model by upregulating M1 markers (such as iNOS+, cluster of differentiation 197, and CD40+) and decreasing M2 markers (including CD163+, Arginase 1, and CD206+). 86 Furthermore, Pue increases TNF-α, proinflammatory cytokine interferon-γ, and interleukin-12 while reducing pro-tumor cytokines IL-4, IL-10 and Figure 3 Schematic of Pue for different pathways.…”