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Lung cancer is the leading cause of cancer death. Pyronaridine, a synthetic drug of artemisinin, has been used in China for over 30 years for the treatment of malaria, but its effect on non-small cell lung cancer (NSCLC) cells is rarely reported. In this study, we determined the efficacy of pyronaridine in four different NSCLC cell lines and explored its mechanism in H1975. The data showed that pyronaridine could upregulate the expression of TNF-related apoptosis-inducing ligand (TRAIL)-mediated death receptor 5 to promote cellular apoptosis. Meanwhile, the JNK (c-Jun N-terminal kinase) level was detected to be significantly increased after treating with pyronaridine. We used JNK inhibitor and found that it could partially inhibit cell apoptosis. The results showed that epidermal growth factor receptor (EGFR), PI3K, and AKT were downregulated after the treatment of pyronaridine. In summary, pyronaridine can selectively kill NSCLC by regulating TRAIL-mediated apoptosis and downregulating the protein level of EGFR. It is a promising anticancer drug for NSCLC., (© 2021 John Wiley & Sons Ltd.)

Cancers illustrating resistance towards apoptosis is one of the main factors causing clinical failure of conventional chemotherapy. Innovative therapeutic methods which can overcome the non-apoptotic phenotype are needed. The AMP-activated protein kinase (AMPK) is the central regulator of cellular energy homeostasis, metabolism, and autophagy. Our previous study showed that the identified natural AMPK activator is able to overcome apoptosis-resistant cancer via autophagic cell death. Therefore, AMPK is an ideal pharmaceutical target for chemoresistant cancers. Here, we unravelled that the bisbenzylisoquinoline alkaloid thalidezine is a novel direct AMPK activator by using biolayer interferometry analysis and AMPK kinase assays. The quantification of autophagic EGFP-LC3 puncta demonstrated that thalidezine increased autophagic flux in HeLa cancer cells. In addition, metabolic stress assay confirmed that thalidezine altered the energy status of our cellular model. Remarkably, thalidezine-induced autophagic cell death in HeLa or apoptosis-resistant DLD-1 BAX-BAK DKO cancer cells was abolished by addition of autophagy inhibitor (3-MA) and AMPK inhibitor (compound C). The mechanistic role of autophagic cell death in resistant cancer cells was further supported through the genetic removal of autophagic gene7 (Atg7). Overall, thalidezine is a novel AMPK activator which has great potential to be further developed into a safe and effective intervention for apoptosis- or multidrug-resistant cancers.

Conventional vaccines are widely used to boost human natural ability to defend against foreign invaders, such as bacteria and viruses. Recently, therapeutic cancer vaccines attracted the most attention for anti-cancer therapy. According to the main components, it can be divided into five types: cell, DNA, RNA, peptide, and virus-based vaccines. They mainly perform through two rationales: (1) it trains the host immune system to protect itself and effectively eradicate cancer cells; (2) these vaccines expose the immune system to molecules associated with cancer that enable the immune system to recognize and destroy cancer cells. In this review, we thoroughly summarized the potential strategies and technologies for developing cancer vaccines, which may provide critical achievements for overcoming the suppressive tumor microenvironment through vaccines in solid tumors. [ABSTRACT FROM AUTHOR]