Pseudolaric acid B exhibits anti-cancer activity on human hepatocellular carcinoma through inhibition of multiple carcinogenic signaling pathways

Hai, Zhang; Jia-chuan, LI; Luo, Han; Zhao, Lin; Zhang, Zhidan; Shen, Xiaofei

doi:10.1016/j.phymed.2018.11.019

Cited by 22 publications

(25 citation statements)

References 41 publications

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“…Targeting upstream kinases is the commonest strategy used to inhibit the activation of STAT3 27 . For example, we previously found that pseudolaric acid B suppressed the phosphorylation of STAT3 by inhibiting the activation of several kinases, including EGFR, Src, ERK, and Akt 19 . Another natural compound, 1β-hydroxyl-5α-chloro-8-epi-xanthatin, also inhibited STAT3 activation via inactivating JAK2 11 .…”

Section: Discussionmentioning

confidence: 99%

“…2c, d). Moreover, obvious apoptotic phenotypes, such as chromatin condensation, nuclear fluorescence, and nuclear fragmentation 11,19 , were observed in α-MGT-treated HepG2 cells ( Fig. 2e).…”

Section: α-Mgt Induces Cell Cycle Arrest and Apoptosis In Hcc Cellsmentioning

confidence: 95%

“…2a, b, treatment with α-MGT-induced G2-M phase arrest in HepG2 and SK-Hep-1 cells in a concentration-dependent manner, respectively. Furthermore, a pro-apoptotic effect is also involved in inhibition of the growth of cancer cells, including HCC cells 11,19 . Hence, we further measured the pro-apoptotic role of α-MGT on HCC cells.…”

Section: α-Mgt Induces Cell Cycle Arrest and Apoptosis In Hcc Cellsmentioning

confidence: 99%

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Anticancer activity of dietary xanthone α-mangostin against hepatocellular carcinoma by inhibition of STAT3 signaling via stabilization of SHP1

et al. 2020

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Hepatocellular carcinoma (HCC) is one of the most lethal human cancers worldwide. The dietary xanthone αmangostin (α-MGT) exhibits potent anti-tumor effects in vitro and in vivo. However, the anti-HCC effects of α-MGT and their underlying mechanisms are still vague. Aberrant activation of signal transducer and activator of transcription 3 (STAT3) is involved in the progression of HCC. We therefore investigated whether α-MGT inhibited the activation of STAT3 and thereby exhibits its anti-HCC effects. In this study, we found that α-MGT significantly suppressed cell proliferation, induced cell cycle arrest, and triggered apoptosis in HCC cells, including HepG2, SK-Hep-1, Huh7, and SMMC-7721 cells in vitro, as well as inhibiting tumor growth in nude mice bearing HepG2 or SK-Hep-1 xenografts. Furthermore, α-MGT potently inhibited the constitutive and inducible activation of STAT3 in HCC cells. In addition, α-MGT also suppressed IL-6-induced dimerization and nuclear translocation of STAT3, which led to inhibition of the expression of STAT3-regulated genes at both mRNA and protein levels. Mechanistically, α-MGT exhibited effective inhibition of the activation of STAT3's upstream kinases, including JAK2, Src, ERK, and Akt. Importantly, α-MGT increased the protein level of Src homology region 2 domain-containing phosphatase-1 (SHP1), which is a key negative regulator of the STAT3 signaling pathway. Furthermore, α-MGT enhanced the stabilization of SHP1 by inhibiting its degradation mediated by the ubiquitin-proteasome pathway. Knockdown of SHP1 using siRNA obviously prevented the α-MGT-mediated inhibition of the activation of STAT3 and proliferation of HCC cells. In summary, α-MGT exhibited a potent anti-HCC effect by blocking the STAT3 signaling pathway via the suppression of the degradation of SHP1 induced by the ubiquitin-proteasome pathway. These findings also suggested the potential of dietary derived α-MGT in HCC therapy.

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Section: Discussionmentioning

confidence: 99%

Section: α-Mgt Induces Cell Cycle Arrest and Apoptosis In Hcc Cellsmentioning

confidence: 95%

Section: α-Mgt Induces Cell Cycle Arrest and Apoptosis In Hcc Cellsmentioning

confidence: 99%

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Anticancer activity of dietary xanthone α-mangostin against hepatocellular carcinoma by inhibition of STAT3 signaling via stabilization of SHP1

et al. 2020

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“…Selective blocking of tumor cell signaling pathways and disrupting its self-regulating growth regulation mechanism has become a hotspot in the field of modern oncological research. Accumulating evidence suggests that the phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling pathway is vital for the growth, metabolism, apoptosis, metastasis, chemotherapy resistance of cancer cells [6,7]. PI3Ks are heterodimers, composed of one p110 catalytic subunit encoded by PIK3CA (p110α), PIK3CB (p110β) or PIK3CD (p110δ) and one p85 regulatory subunit encoded by PIK3R1 (p85α), PIK3R2 (p85β) or PIK3R3 (p85γ) [8].…”

Section: Introductionmentioning

confidence: 99%

Erianin suppresses hepatocellular carcinoma cells through down-regulation of PI3K/AKT, p38 and ERK MAPK signaling pathways

Yang

Zhou

et al. 2020

Bioscience Reports

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Background: Hepatocellular carcinoma (HCC) is the dominant pathological type of primary liver cancer and no effective methods are available for its treatment. Erianin is a natural product extracted from Dendrobium, which possesses multiple pharmacological activities, including antioxidative and antitumor activity. Objective: To evaluate the anti-HCC activities of erianin and explore its underlying mechanism. Methods: MTT assay and Crystal Violet staining assay were used to select the non-toxic concentrations for the subsequent experiments. The colony formation assay and PCNA fluorescent staining were used to investigate the antiproliferative effects of erianin on human SMMC-7721 and HepG2 cells. Wound healing and transwell test were used to analyze cell migration and invasion. Caspase3 and Tunel staining were used to detect apoptosis. Western blot was used to examine the expression levels of proteins associated with invasion and key proteins in the phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), p38 and ERK mitogen-activated protein kinase (MAPK) signaling pathways. Results: Erianin inhibited HCC cell proliferation in a dose-dependent manner. Decreased migration rate and invaded cells were observed with erianin supplement. The expression of invasion-associated proteins in the erianin group was also down-regulated. Besides, more apoptotic cells were observed after erianin treatment. For the molecular mechanism, erianin inhibited the phosphorylation of Akt, ERK and P38 in the PI3K/Akt and ERK/P38 pathway. Conclusion: We demonstrated, for the first time, that erianin inhibited the proliferation, migration, invasion and induced the apoptosis of HCC through PI3K/Akt, p38 and ERK MAPK signaling pathway, indicating that erianin is a promising agent for the HCC treatment.

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“…The results showed that compound 1 was able to upregulate the expression of the proapoptotic protein Bax but downregulated the expression of antiapoptotic protein Bcl-2 (Figure 4A,D,E). Caspase-3 can be activated by upstream apoptotic signaling, which cleaves various cellular substrates such as poly ADP-ribose polymerase(PARP) [22]. Furthermore, this study showed that the expressions of cleaved caspase-3 and cleaved PARP were significantly enhanced in compound 1 -treated HepG2 cells (Figure 4A–C).…”

Section: Resultsmentioning

confidence: 93%

Benzophenones from Anemarrhena asphodeloides Bge. Exhibit Anticancer Activity in HepG2 Cells via the NF-κB Signaling Pathway

Liao

Chen

et al. 2019

Molecules

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A chemical investigation of the fibrous roots of Anemarrhena asphodeloides Bge. led to the isolation of four benzophenones, including one new compound (1) and three known ones (2–4). Comprehensive 1D, 2D NMR and HRESIMS data established the structures of the isolated compounds. The absolute configurations were determined by comparison of the calculated optical rotation (OR) with experimental data. All the isolates were evaluated for their cytotoxicities on hepatocellular carcinoma cell lines (HepG2 and Hep3B). Compound 1 showed strong cytotoxicity against HepG2 and Hep3B cells, with IC50 values at 153.1 and 180.6 nM. Through MTT assay, flow cytometry and Western blot analysis, compound 1 demonstrated the ability to stimulate apoptosis via the NF-κB signaling pathway in HepG2 cells. These benzophenones are potential lead compounds for the development of better treatments for hepatocellular carcinoma.

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Pseudolaric acid B exhibits anti-cancer activity on human hepatocellular carcinoma through inhibition of multiple carcinogenic signaling pathways

Cited by 22 publications

References 41 publications

Anticancer activity of dietary xanthone α-mangostin against hepatocellular carcinoma by inhibition of STAT3 signaling via stabilization of SHP1

Anticancer activity of dietary xanthone α-mangostin against hepatocellular carcinoma by inhibition of STAT3 signaling via stabilization of SHP1

Erianin suppresses hepatocellular carcinoma cells through down-regulation of PI3K/AKT, p38 and ERK MAPK signaling pathways

Benzophenones from Anemarrhena asphodeloides Bge. Exhibit Anticancer Activity in HepG2 Cells via the NF-κB Signaling Pathway

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