Cucurbitacin I exerts its anticancer effects by inducing cell cycle arrest via the KAT2a-ube2C/E2F1 pathway and inhibiting HepG2-induced macrophage M2 polarization

Article

作者: Wei, Jinfen ; Liu, Yunfei ; Ding, Ke ; Liang, Keying ; Qiu, Li ; Chen, Zixi ; Du, Hongli ; Gong, Xiaocheng

Hepatocellular carcinoma (HCC) is one of the most common malignancies globally, particularly prevalent in China, where it accounts for nearly half of the world's new cases and deaths each year, but has limited therapeutic options. This study systematically investigated the impact of cucurbitacin I on HCC cell lines including SK-Hep-1, Huh-7, and HepG2. The results revealed that cucurbitacin I not only inhibited cell proliferation, cell migration and colony formation, but also induced apoptosis in HCC cells. The apoptotic induction was accompanied by a decrease in the expression of the anti-apoptotic factor B-cell lymphoma 2 (Bcl2), and an elevation in the expression levels of pro-apoptotic factors, including tumor protein p53 (P53), bcl2 associated X-apoptosis regulator (Bax), and caspase3 (Cas3). Additionally, cucurbitacin I caused cell cycle arrest by modulating the lysine acetyltransferase 2A (KAT2A)-E2F transcription factor 1 (E2F1)/Ubiquitin-conjugating enzyme E2 C (UBE2C) signaling axis. In terms of regulation on tumor microenvironment, cucurbitacin I was demonstrated the ability to inhibit HCC cell-induced M2 polarization of macrophages. This comprehensive study unveils the multifaceted anti-cancer mechanisms of cucurbitacin I, providing robust support for its potential application in the treatment of HCC, offering new avenues for the future development of HCC treatment strategies.

2024-12-01·Photodiagnosis and Photodynamic Therapy

Photobiomodulation reduces spinal cord edema by decreasing the expression of AQP4 in the astrocytes of male spinal cord injury rats via the JAK2/STAT3 signaling pathway

Article

作者: Ju, Cheng ; Ma, Yangguang ; Yang, YongYong ; Wang, Zhe ; Yang, Yongyong ; Hu, Xueyu ; Zhang, Zhihao ; Wang, Xuankang ; Zhang, ZhiHao ; Zuo, Xiaoshuang ; Wu, Tingyu ; Zhou, Jie

BACKGROUNDSpinal cord swelling commonly occurs following SCI. Previous studies suggest that PBM may reduce inflammation and scar formation after SCI. However, whether PBM can alleviate post-spinal cord injury edema and its underlying mechanisms have not yet been reported. This study aims to investigate the effects of PBM on spinal cord swelling in rats following SCI and explore the underlying mechanisms.METHODSA rat model of SCI was established, and the rats received continuous PBM therapy for two weeks. Tissue hydration, motor function, AQP4 expression, and pathological changes in the spinal cord were evaluated at different time points. In vitro, astrocytes were subjected to PBM and treated with either cucurbitacin I or TGN020 following OGD.RESULTSThe results indicate that PBM reduces tissue swelling in rats with SCI, improves motor function recovery, and inhibits the upregulation of AQP4 and GFAP associated with SCI. In vitro, PBM reduces abnormal activation of the JAK2/STAT3 signaling pathway in astrocytes, leading to decreased AQP4 synthesis and astrocyte activation.CONCLUSIONSThese findings suggest that PBM reduces spinal cord swelling in rats after injury. This effect is associated with the inhibition of JAK2/STAT3 signaling pathway activation in astrocytes and the reduction in AQP4 expression.

2024-11-01·Journal of Chemical Ecology

Cultivar-Specific Defense Responses in Wild and Cultivated Squash Induced by Belowground and Aboveground Herbivory

Article

作者: Bruno, Pamela ; Di Caprio, Leandro ; Jaccard, Charlyne ; Bustos-Segura, Carlos ; Benrey, Betty ; Arce, Carla C M ; Ye, Wenfeng

AbstractPlant domestication often alters plant traits, including chemical and physical defenses against herbivores. In squash, domestication leads to reduced levels of cucurbitacins and leaf trichomes, influencing interactions with insects. However, the impact of domestication on inducible defenses in squash remains poorly understood. Here, we investigated the chemical and physical defensive traits of wild and domesticated squash (Cucurbita argyrosperma), and compared their responses to belowground and aboveground infestation by the root-feeding larvae and the leaf-chewing adults of the banded cucumber beetle Diabrotica balteata (Coleoptera: Chrysomelidae). Wild populations contained cucurbitacins in roots and cotyledons but not in leaves, whereas domesticated varieties lacked cucurbitacins in all tissues. Belowground infestation by D. balteata larvae did not increase cucurbitacin levels in the roots but triggered the expression of cucurbitacin biosynthetic genes, irrespective of domestication status, although the response varied among different varieties. Conversely, whereas wild squash had more leaf trichomes than domesticated varieties, the induction of leaf trichomes in response to herbivory was greater in domesticated plants. Leaf herbivory varied among varieties but there was a trend of higher leaf damage on wild squash than domesticated varieties. Overall, squash plants responded to both belowground and aboveground herbivory by activating chemical defense-associated gene expression in roots and upregulating their physical defense in leaves, respectively. While domestication suppressed both chemical and physical defenses, our findings suggest that it may enhance inducible defense mechanisms by increasing trichome induction in response to herbivory.

100 项与葫芦素I 相关的药物交易

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