Perspectives and controversies regarding the use of natural products for the treatment of lung cancer

Wen, Tingting; Song, Lei; Hua, Shucheng

doi:10.1002/cam4.3660

Cited by 43 publications

(26 citation statements)

References 260 publications

(301 reference statements)

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“…Thus, the levels of MDA, GSH, and TEAC were measured in PMAstimulated neutrophils at different concentrations of ZIN and we found that ZIN significantly inhibited oxidative stress. Nrf2 signaling plays a pivotal role in modulating the redox hemostasis, which is targeted by a large cohort of antioxidant natural compounds [59][60][61]. Previously, we reported that ZIN activates the Nrf2 signaling pathway in airway epithelial cells, contributing to its antiasthmatic effects in mice [24].…”

Section: Discussionmentioning

confidence: 99%

Zingerone Inhibits the Neutrophil Extracellular Trap Formation and Protects against Sepsis via Nrf2-Mediated ROS Inhibition

Zhu

Wang

Luo

et al. 2022

Oxidative Medicine and Cellular Longevity

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Neutrophils release chromatin and antimicrobial proteins to trap and kill microbes, which is termed as neutrophil extracellular trap (NET) formation. NETs play a pivotal role in host defense against infection. However, emerging evidence indicated that NETs also contribute to an exaggerated inflammatory response and organic injuries in sepsis. Zingerone, a natural compound extracted from Zingiber officinale, exerts antioxidant, anti-inflammatory, and antioncogenic properties. In this study, we found that treatment with zingerone reduced organ injury and improved the outcome in a cecal ligation puncture- (CLP-) induced polymicrobial sepsis model. Administration of zingerone also alleviates reactive oxygen species (ROS) accumulation and systematic inflammation in septic mice and inhibits neutrophil extracellular traps (NETs) formation in vivo and in vitro. Furthermore, inhibition of nuclear factor erythroid 2-related factor 2 (Nrf2) with its specific antagonist significantly counteracted the suppressive effects of zingerone on ROS and NETs and retarded the protective role of zingerone against sepsis-associated organ injury. In addition, exposure to zingerone does not affect phagocytic activity of neutrophils in vitro and bacterial dissemination in vivo. Above all, our results indicate that zingerone treatment obviously attenuates NET formation and inflammatory response via Nrf2-mediated ROS inhibition, thus providing a novel therapeutic strategy against sepsis-induced injury.

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Section: Discussionmentioning

confidence: 99%

Zingerone Inhibits the Neutrophil Extracellular Trap Formation and Protects against Sepsis via Nrf2-Mediated ROS Inhibition

Zhu

Wang

Luo

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Lung cancer is responsible for around 20% of all cancer deaths with an estimated 1.8 million new cases and 1.6 million deaths annually ( Oak et al, 2012 ; Hirsch et al, 2017 ). The pace of the annual decline in lung cancer mortality doubled from 2.4% (during 2009 through 2013) to 5.0% (during 2014 through 2018) due to the advances in diagnostics and therapy, and this trend coincides with the steady declined incidence (2.2–2.3%) ( Siegel et al, 2021 ; Wen et al, 2021 ). However, even lung cancer is diagnosed in the early stages, around one in four patients develop relapse and most of them die from recurrent disease (the overall 5-years survival rates are only around 15%) ( Gray et al, 2019 ; Bade and Dela Cruz, 2020 ; Coakley and Popat, 2020 ; Schegoleva et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Anti-Lung Cancer Evaluation of 1, 2, 3-Triazole Tethered Dihydroartemisinin-Isatin Hybrids

Hou

et al. 2021

Front. Pharmacol.

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A series of 1,2,3-triazole tethered dihydroartemisinin-isatin hybrids 8a-c and 9a-k were designed and synthesized. Their antiproliferative activity against A549, doxorubicin-resistant A549 (A549/DOX) as well as cisplatin-resistant A549 (A549/DDP) lung cancer cell lines was also investigated in this study. All hybrids (half maximal inhibitory concentration/IC50: 7.54–73.8 μM) were more potent than the parent drug dihydroartemisinin (IC50: 69.4–88.0 μM) and also non-cytotoxic towards mouse embryonic fibroblast cells NIH/3T3 (IC50: >100 μM). The structure-activity relationships illustrated that the substituents on C-3 and C-5 position of isatin moiety influenced the activity significantly. Imine at C-3 position decreased the activity, whereas fluoro at C-5 position enhanced the activity. In particular, hybrids 8a,c (IC50: 7.54–12.1 μM) and 9i (IC50: 9.10–15.9 μM) were comparable to cisplatin (IC50: 7.54–15.9 μM vs 9.38–19.7 μM) against A549 and A549/DOX, but 4.6–7.6 folds more potent than that of cisplatin (IC50: 8.77–14.3 μM vs 66.9 μM) against A549/DDP cells. Moreover, hybrids 8a,c exhibited excellent stability (liver microsomes: 68–83%) in mouse/human microsomes and good pharmacokinetic properties, demonstrating their potential as a novel anti-lung cancer chemotherapeutic candidates.

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“…Accumulating evidence has shown that phytochemical compounds from natural sources are remarkably effective in treating malignancies and other diseases [ 4 – 7 ]. The most successful example is paclitaxel, a diterpenoid isolated from the Taxus brevifolia bark for the first time in 1971 [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Bixin Prevents Colorectal Cancer Development through AMPK-Activated Endoplasmic Reticulum Stress

Qiu

Chang-feng

Zhang

2022

BioMed Research International

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Chemicals isolated from natural products have been broadly applied in the treatment of colorectal cancer (CRC). Bixin, an apocarotenoid from the seeds of Bixa orellana, exerts multiple pharmacological properties, including neuroprotective, anti-inflammatory, cardioprotective, and antitumor effects; yet, the therapeutic effects of Bixin on CRC are still unknown. Here, we described that Bixin treatment significantly inhibited the proliferation and motility of two CRC cell lines (CaCO2 and SW480) in vitro and in vivo. In addition, Bixin administration has sensitized CRC cells to TNF-related apoptosis-inducing ligand- (TRAIL-) induced cell apoptosis. Moreover, we showed that Bixin treatment initiated the activation of PERK/eIF-2α signal in CaCO2 and SW480 cells, leading to endoplasmic reticulum stress-associated apoptosis. Pharmacological inhibition of AMP-activated protein kinase (AMPK) abrogated the Bixin-induced activation of protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 alpha (eIF-2α) pathway, as well as reversed the inhibitory effects of Bixin on CRC development. In conclusion, this study indicated that Bixin treatment inhibits the progression of CRC through activating the AMPK/PERK/eIF-2α pathway, providing a novel potential strategy for clinical prevention of CRC.

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Perspectives and controversies regarding the use of natural products for the treatment of lung cancer

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 43 publications

References 260 publications

Zingerone Inhibits the Neutrophil Extracellular Trap Formation and Protects against Sepsis via Nrf2-Mediated ROS Inhibition

Zingerone Inhibits the Neutrophil Extracellular Trap Formation and Protects against Sepsis via Nrf2-Mediated ROS Inhibition

Design, Synthesis and Anti-Lung Cancer Evaluation of 1, 2, 3-Triazole Tethered Dihydroartemisinin-Isatin Hybrids

Bixin Prevents Colorectal Cancer Development through AMPK-Activated Endoplasmic Reticulum Stress

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