A curcumin derivative, WZ35, suppresses hepatocellular cancer cell growth<i>via</i>downregulating YAP-mediated autophagy

Wang, Lihua; Zhu, Zheng; Liang, Han; Zhao, Liqian; Weng, Juyang; Yang, Hongbao; Wu, Shijia; Chen, Kaiyuan; Wu, Liang; Chen, Tongke

doi:10.1039/c8fo02448k

Cited by 27 publications

(21 citation statements)

References 54 publications

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“…Similarly, numerous previous in vitro and in vivo studies have demonstrated that curcumin inhibits the growth cancer in both animals and humans (40-42), including hepatocellular carcinoma (43). Several reports have suggested that curcumin or its derivative alone or in combination with other drugs exhibit favorable anti-liver cancer activity (44)(45)(46). Shao et al (47) reported that bisdemethoxycurcumin, a natural dimethoxy derivative of curcumin, decreases the number of tumor-infiltrating MDSCs in MB49 metastasized bladder cancer cells.…”

Section: Discussionmentioning

confidence: 91%

Curcumin inhibits the growth of liver cancer by impairing myeloid‑derived suppressor cells in murine tumor tissues

et al. 2021

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Curcumin, one of the active ingredients of Curcuma longa (Jianghuang), has been reported to exert multiple bioactivities, including pro-apoptotic and anti-inflammatory activities. In recent years, curcumin has been extensively studied, and it has been revealed that curcumin inhibits the growth of numerous types of cancer. However, to the best of our knowledge, the inhibitory effects of curcumin on the activation or expansion of myeloid-derived suppressor cells (MDSCs) in liver cancer and the underlying mechanism have not yet been determined. Therefore, the present study aimed to investigate the inhibitory effect of curcumin on MDSC activity and the associated anti-neoplastic mechanism in a HepG2 ×enograft mouse model. The effect of curcumin on the viability of Huh-7, MHCC-97H and HepG2 cells in vitro was analyzed using a Cell Counting Kit-8 assay. The effects of curcumin on tumor growth, numbers of MDSCs, expression levels of proteins involved in the toll-like receptor 4 (TLR4)/NF-κB signaling pathway, levels of related inflammatory factors and angiogenesis were determined in HepG2 ×enograft model mice, which were given different doses of curcumin via intragastrical administration. The results of the present study revealed that curcumin inhibited the viability of Huh-7, MHCC-97H and HepG2 cells and the growth of HepG2 ×enograft tumors in mice. Flow cytometric analysis indicated that curcumin reduced the number of MDSCs in mouse xenograft tumors. In addition, the results demonstrated that curcumin inhibited the TLR4/NF-κB signaling pathway and the expression of inflammatory factors, including IL-6, IL-1β, prostaglandin E2 and cyclooxygenase-2, in mouse xenograft tumors. Furthermore, curcumin suppressed the secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-colony stimulating factor (G-CSF), which are essential factors for MDSCs modulation, in tumor tissues. Additionally, curcumin was revealed to inhibit angiogenesis, which was demonstrated by the downregulation of the expression levels of vascular endothelial growth factor, CD31 and α-smooth muscle actin in western blotting, immunohistochemistry and immunofluorescence experiments. In conclusion, the findings of the present study identified a novel mechanism via which curcumin may suppress the growth of liver cancer by reducing the numbers of MDSCs and subsequently disrupting the process of angiogenesis. These conclusions were supported by the observed inactivation of the TLR4/NF-κB signaling pathway-mediated inflammatory response and the downregulation of GM-CSF and G-CSF secretion in xenograft tissues.

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Section: Discussionmentioning

confidence: 91%

Curcumin inhibits the growth of liver cancer by impairing myeloid‑derived suppressor cells in murine tumor tissues

et al. 2021

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“…When administered to BALB/c nude mice bearing HCCLM3 cells, WZ35 (20 mg/kg, i.p.) suppressed tumor growth more efficiently than curcumin and large areas of necrosis were present in treated tumors [237].…”

Section: Curcuminoidsmentioning

confidence: 95%

Polyphenol-Mediated Autophagy in Cancer: Evidence of In Vitro and In Vivo Studies

Benvenuto

Albonici

Focaccetti

et al. 2020

IJMS

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One of the hallmarks of cellular transformation is the altered mechanism of cell death. There are three main types of cell death, characterized by different morphological and biochemical features, namely apoptosis (type I), autophagic cell death (type II) and necrosis (type III). Autophagy, or self-eating, is a tightly regulated process involved in stress responses, and it is a lysosomal degradation process. The role of autophagy in cancer is controversial and has been associated with both the induction and the inhibition of tumor growth. Autophagy can exert tumor suppression through the degradation of oncogenic proteins, suppression of inflammation, chronic tissue damage and ultimately by preventing mutations and genetic instability. On the other hand, tumor cells activate autophagy for survival in cellular stress conditions. Thus, autophagy modulation could represent a promising therapeutic strategy for cancer. Several studies have shown that polyphenols, natural compounds found in foods and beverages of plant origin, can efficiently modulate autophagy in several types of cancer. In this review, we summarize the current knowledge on the effects of polyphenols on autophagy, highlighting the conceptual benefits or drawbacks and subtle cell-specific effects of polyphenols for envisioning future therapies employing polyphenols as chemoadjuvants.

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“…Numerous papers have examined the natural phytopolyphenol, curcumin, in terms of its antitumorigenesis and therapeutic properties [471]. Administration of curcumin to Huh7 cells precipitated early autophagy, as evidenced by autophagic vacuolar evolution [472].…”

Section: Targeting Autophagymentioning

confidence: 99%

Targeting Drug Chemo-Resistance in Cancer Using Natural Products

et al. 2021

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Cancer is one of the leading causes of death globally. The development of drug resistance is the main contributor to cancer-related mortality. Cancer cells exploit multiple mechanisms to reduce the therapeutic effects of anticancer drugs, thereby causing chemotherapy failure. Natural products are accessible, inexpensive, and less toxic sources of chemotherapeutic agents. Additionally, they have multiple mechanisms of action to inhibit various targets involved in the development of drug resistance. In this review, we have summarized the basic research and clinical applications of natural products as possible inhibitors for drug resistance in cancer. The molecular targets and the mechanisms of action of each natural product are also explained. Diverse drug resistance biomarkers were sensitive to natural products. P-glycoprotein and breast cancer resistance protein can be targeted by a large number of natural products. On the other hand, protein kinase C and topoisomerases were less sensitive to most of the studied natural products. The studies discussed in this review will provide a solid ground for scientists to explore the possible use of natural products in combination anticancer therapies to overcome drug resistance by targeting multiple drug resistance mechanisms.

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A curcumin derivative, WZ35, suppresses hepatocellular cancer cell growthviadownregulating YAP-mediated autophagy

Abstract: HCC is a common cancer type in the world. Here, we found WZ35, a novel derivative of curcumin, could notably suppress HCC cell growthviainhibiting YAP controlled autophagy, highlighting the potent anti-tumor activity of WZ35 in liver cancer therapy.

Cited by 27 publications

References 54 publications

Curcumin inhibits the growth of liver cancer by impairing myeloid‑derived suppressor cells in murine tumor tissues

Curcumin inhibits the growth of liver cancer by impairing myeloid‑derived suppressor cells in murine tumor tissues

Polyphenol-Mediated Autophagy in Cancer: Evidence of In Vitro and In Vivo Studies

Targeting Drug Chemo-Resistance in Cancer Using Natural Products

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