The Cytotoxicity Mechanism of 6-Shogaol-Treated HeLa Human Cervical Cancer Cells Revealed by Label-Free Shotgun Proteomics and Bioinformatics Analysis

Li, Qun; Peng, Yongbo; Qi, Lian‐Wen; Cheng, Xiaolan; Xu, Xiaojun; Liu, Lele; Liu, E‐Hu; Li, Ping

doi:10.1155/2012/278652

Cited by 28 publications

(17 citation statements)

References 36 publications

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“…of human cancer cell lines in vitro (6)(7)(8). Previous studies have demonstrated that 6-shogaol induced apoptosis of hepatocellular carcinoma and cervical cancer via endoplasmic reticulum stress (9,10). Additionally, increasing evidences have demonstrated that this plant polyphenol is a potent blocker of the NF-κB pathway (6,11,12).…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

Antitumor Activity of Gemcitabine Can Be Potentiated in Pancreatic Cancer through Modulation of TLR4/NF-κB signaling by 6-Shogaol

Zhou

Jiang

et al. 2014

AAPS J

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Advanced pancreatic cancer still has a poor prognosis, even with the approval of several drugs, such as gemcitabine. Therefore, developing effective and safe antitumor agents is urgently needed. 6-Shogaol, a phenol extracted from ginger, has been linked to suppression of proliferation and survival of cancer with different mechanisms. In the present study, we investigated whether 6-shogaol could suppress pancreatic cancer progress and potentiate pancreatic cancer to gemcitabine treatment in vitro and in vivo. We found that 6-shogaol prevented the activation of toll like receptor 4 (TLR4)/NF-κB signaling. The modulation of NF-κB signaling by 6-shogaol was ascertained by electrophoretic mobility shift assay and western blot analysis. The suppression of NF-κB signaling and key cell survival regulators including COX-2, cyclinD1, survivin, cIAP-1, XIAP, Bcl-2, and MMP-9 brought the anti-proliferation effects in pancreatic cancer cells and sensitized them to gemcitabine treatment. Furthermore, in a pancreatic cancer xenograft model, we found a decreased proliferation index (Ki-67) and increased apoptosis by TUNEL staining in 6-shogaol treated tumors. It was also shown that 6-shogaol combined with gemcitabine treatment was more effective than drug alone, consistent with the downregulation of NF-κB activity along with its target genes COX-2, cyclinD1, survivin, cIAP-1, and XIAP. Overall, our results suggest that 6-shogaol can inhibit the growth of human pancreatic tumors and sensitize them to gemcitabine by suppressing of TLR4/NF-κB-mediated inflammatory pathways linked to tumorigenesis.

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Section: Electronic Supplementary Materialsmentioning

confidence: 99%

Antitumor Activity of Gemcitabine Can Be Potentiated in Pancreatic Cancer through Modulation of TLR4/NF-κB signaling by 6-Shogaol

Zhou

Jiang

et al. 2014

AAPS J

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“…Studies have previously shown that 6-Shogaol has anti-proliferative, anti-survival, and pro-apoptotic effects on many different types of human cancer cells, such as SMMC-7721 (liver), HGC (gastric), A2780 (ovarian), COLO 205 (colon), A549 (lung), HeLa (cervix), and MDA-MB-231 (breast) [ 30 , 31 , 32 , 39 , 41 , 42 , 43 ]. The known molecular mechanisms underlying 6-Shogaol’s anticancer effects include the induction of apoptosis, the activation of caspase-9, -8, -3, the accumulation of sub G1 phase cells [ 30 , 42 , 43 , 44 , 45 , 46 ], and the arrest of the cell cycle [ 47 ]. Through initial experiments, we herein have demonstrated that 6-Shogaol at 20 μM largely reduces the survival of SW872 and 93T449 human liposarcoma cells, but it does not affect normal 3T3-L1 preadipocytes, suggesting the specificity of 6-Shogaol to inhibit adipocytic tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Anti-Survival and Pro-Apoptotic Effects of 6-Shogaol on SW872 Human Liposarcoma Cells via Control of the Intrinsic Caspase Pathway, STAT-3, AMPK, and ER Stress

Yadav

Jang

2020

Biomolecules

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Notably, 6-Shogaol, a bioactive natural substance, has anticancer effects on many types of tumors. Up to date, the anticancer effect and mode of action of 6-Shogaol on liposarcoma are not known. In this study, we investigated whether 6-Shogaol inhibits the growth of SW872 and 93T449 cells, two different human liposarcoma cell lines. Of note, 6-Shogaol inhibited the growth of SW872 and 93T449 cells without affecting that of normal 3T3-L1 preadipocytes. Specifically, 6-Shogaol further induced the apoptosis of SW872 cells, as evidenced by nuclear DNA fragmentation, increased sub G1 population, activation of the intrinsic caspase pathway, and PARP cleavage. However, pretreatment with either z-VAD-fmk, a pan-caspase inhibitor, or N-acetylcysteine, an antioxidant, attenuated the 6-Shogaol’s growth-suppressive and apoptosis-inducing effects on SW872 cells. Moreover, 6-Shogaol activated AMPK while inhibited STAT-3 in SW872 cells, and siRNA-based genetic silencing of AMPK or STAT-3 considerably blocked the growth-suppressive and apoptotic response of 6-Shogaol to SW872 cells. Moreover, 6-Shogaol also upregulated the expression and phosphorylation of GRP-78, eIF-2α, ATF4, and CHOP, known ER stress markers, in SW872 cells, illustrating the induction of ER stress. These findings collectively demonstrate that 6-Shogaol has strong antigrowth and proapoptotic effects on SW872 cells through regulation of the intrinsic caspase pathway, oxidative stress, STAT-3, AMPK, and ER stress.

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“…The activities of various natural dietary agents, especially spices and herbs, in health promotion, including the suppression of cancer, have attracted considerable attention (16). Liu et al (17) reported that 6-shogaol, a natural compound isolated from the rhizome of ginger, induced apoptosis and G 2 /M-phase cell-cycle arrest in human cervical cancer (HeLa) cells. In a proteomic analysis, they found that the peak intensities of 76 proteins in HeLa cells changed (54 upregulated and 22 downregulated) by more than two-fold after treatment for 24 h with 15 μM 6-shogaol, relative to their levels in vehicle-treated cells.…”

Section: Roles Of 14-3-3 Proteins In the Treatment Of Cervical Cancermentioning

confidence: 99%

The role of 14-3-3 proteins in gynecological tumors

Zhang¹,

Shen²,

Chen³

et al. 2015

Front Biosci

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A large family of highly conserved cellular 14-3-3 proteins plays key roles in the regulation of central physiological pathways such as metabolism, protein trafficking, signal transduction, apoptosis and regulation of cell cycle. The involvement of these proteins in the regulation of various tumor suppressor genes and oncogenes points to their potential role in human cancer. According to some, the 14-3-3 proteins in gynecological tumors, promote gynecological tumors whereas others suggest that 14-3-3 proteins function as tumor suppressors in such tumors. Here, we review the use of 14-3-3 proteins as novel markers for screening and early diagnosis of gyncyological malignancies, and in monitoring the effectiveness of treatment. 14-3-3 proteins are proposed to be used as prognostic factors and as specific target in the treatment of cancers.

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The Cytotoxicity Mechanism of 6-Shogaol-Treated HeLa Human Cervical Cancer Cells Revealed by Label-Free Shotgun Proteomics and Bioinformatics Analysis

Cited by 28 publications

References 36 publications

Antitumor Activity of Gemcitabine Can Be Potentiated in Pancreatic Cancer through Modulation of TLR4/NF-κB signaling by 6-Shogaol

Antitumor Activity of Gemcitabine Can Be Potentiated in Pancreatic Cancer through Modulation of TLR4/NF-κB signaling by 6-Shogaol

Anti-Survival and Pro-Apoptotic Effects of 6-Shogaol on SW872 Human Liposarcoma Cells via Control of the Intrinsic Caspase Pathway, STAT-3, AMPK, and ER Stress

The role of 14-3-3 proteins in gynecological tumors

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