Design, synthesis, and molecular hybrids of caudatin and cinnamic acids as novel anti-hepatitis B virus agents

Wang, Lijun; Geng, Chang‐An; Ma, Yun‐Bao; Luo, Jie; Huang, Xiaoyan; Chen, Hao; Zhou, Nan; Zhang, Xuemei

doi:10.1016/j.ejmech.2012.05.012

Cited by 39 publications

(14 citation statements)

References 64 publications

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“…In our previous studies, caudatin induced apoptosis of AGS cells or the HGC-27 cell line (14). Wang et al found that caudatin had an inhibitory activity on the secretion of HBsAg and HBV DNA replication (17). Furthermore, caudatin as a prospective anti-HCC drug with the mechanism of inhibiting cell proliferation and inducing cell apoptosis has been reported (18).…”

Section: Introductionmentioning

confidence: 91%

Caudatin targets TNFAIP1/NF-κB and cytochrome c/caspase signaling to suppress tumor progression in human uterine cancer

Tan

Xie

et al. 2016

International Journal of Oncology

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Caudatin, a C-21 steroidal glyco-side isolated from Chinese herbs, has a long history of use for the treatment of multiple diseases, including cancers. However, the precise mechanisms of actions of caudatin in human uterine cancer cells remain unclear. In this study, we investigated the molecular mechanisms by which caudatin inhibits cell growth in human cervical carcinoma cell line (HeLa) and endometrial carcinoma cell line (HEC-1A). Treatment with caudatin promoted cell morphology change, inhibited cell proliferation, colony formation, migration and spheroid formation, and induced cell apoptosis. Our results showed that the expression of tumor necrosis factor; α-induced protein 1 (TNFAIP1) was downregulated in uterine cancer cells and tissues compared to paired adjacent non-tumor uterine tissues. Further molecular mechanism study showed that caudatin can directly regulate TNFAIP1 expression in a concentration-dependent manner and also associated with the downregulation of NF-κB and upregulation of BAX/BcL-2 ratio and caspase-3. Moreover, we found that overexpression of TNFAIP1 inhibits the growth and invasion, and induces apoptosis in uterine cancer cells through inhibition of the NF-κB pathway, suggesting that TNFAIP1 may act as a potential therapeutic target for the treatment of cancer. We found that caudatin inhibited tumorigenicity and upregulated TNFAIP1 in vivo. Taken together, caudatin impacts on cell proliferation, migration and apoptosis of uterine cancer cells by regulating several carcinogenesis-related processes, including a novel mechanism involving the targeting of TNFAIP1/NF-κB signaling. Our findings provide new insights into understanding the anticancer mechanisms of caudatin in human uterine cancer therapy.

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Section: Introductionmentioning

confidence: 91%

Caudatin targets TNFAIP1/NF-κB and cytochrome c/caspase signaling to suppress tumor progression in human uterine cancer

Tan

Xie

et al. 2016

International Journal of Oncology

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“…The [M−H] − ions for metaplexigenin (1), caudatin (2), qingyangshengenin (3), and penupogenin (4) were easily obtained. In contrast, only [M+H] + ions for 20-cinnamoylsarcostin (5) and gagamine (6) were observed. Therefore, the MS n investigations for steroids 1-4 in negative mode and for steroids 5-6 in positive mode were chosen, as shown in Tables 1-6.…”

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confidence: 98%

A Fragmentation Study of Six C₂₁ Steroidal Aglycones by Electrospray Ionization Ion-Trap Time-of-Flight Tandem Mass Spectrometry

Chen

Geng

2015

Natural Product Communications

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The fragmentation patterns of six C 21 steroidal aglycones, metaplexigenin (1), caudatin (2), qingyangshengenin (3), penupogenin (4), 20-cinnamoylsarcostin (5), and gagamine (6), were analyzed by high-resolution electrospray ionization ion-trap time-of-flight tandem mass spectrometry (HR-ESI-IT-TOF-MS n). The [M-H] + ions of steroids 1-3 that contain a carbonyl functional group at C-20 (Type I) and [M+H] + ions of steroids 5-6 that possess a hydroxyl group at C-20 (Type II) were readily observed in MS analyses. The fragmentation pathways and diagnostic fragment ions for these six steroidal aglycones were proposed on the basis of their MS n analyses. The common fragmentation pathways for type I steroidal aglycones include the neutral loss of the ester group at C-12 and the hydroxyl moieties on the steroid skeleton, as well as the cleavage of ring D. Their diagnostic fragment ions were identified as m/z 361(B), 343 (C), 325 (D), 307 (F), 283 (G), 259 (E), and 243 (H). The fragmentation behavior of penupogenin (4) in type II was similar to those of type I, with m/z 363 (B'), 345 (C'), 327 (D'), 309 (F'), 283 (G), and 243 (H) as its diagnostic fragment ions. The ester group at C-20 was difficult to cleave in the MS n analyses of 20-cinnamoylsarcostin (5) and gagamine (6) so that the loss of this ester group was slower than that at C-12 and hydroxyl groups; the key ions at m/z 329 (I), 311 (J), 293 (K), and 275 (L) were characteristic for 5 and 6. The base ion peaks were derived from the loss of the substituent group at either C-12 or C-17 for both type I and type II steroidal aglycones.

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“…Recent studies demonstrated that caudatin induced the apoptosis of HepG2 cells or the SMMC772 cell line (6,7). Wang et al (8) found that caudatin had an inhibitory activity on the secretion of HBsAg and HBV DNA replication. Furthermore, caudatin as a prospective anti-HCC drug with the mechanism of inhibiting cell proliferation and inducing cell apoptosis has been reported (9).…”

mentioning

confidence: 99%

Caudatin induces cell apoptosis in gastric cancer cells through modulation of Wnt/β-catenin signaling

Zhang

Liu

et al. 2013

Oncology Reports

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Abstract. Caudatin has been reported to trigger apoptosis in several types of cancer cell lines. In the present study, we investigated whether caudatin has therapeutic value in gastric cancer and examined the effects of caudatin on the expression of β-catenin in human gastric carcinoma cell lines. Here, we showed that caudatin treatment resulted in a dose-and time-dependent inhibition of proliferation of the gastric carcinoma cell lines. Cell cycle analysis demonstrated that caudatin induced G0/G1 arrest and downregulated CDK2 levels. In contrast, the expression of the p21 protein was increased. AGS cells treated with caudatin exhibited typical characteristics of apoptosis, which were accompanied by activation of caspase-3, -8, -9 and PARP. Western blot analysis and immunocytochemical staining showed that caudatin induced a reduction in β-catenin expression and this reduction was due to proteosome-mediated degradation. This reduction in β-catenin activation was due to the downregulation of its downstream targets cyclinD1 and c-MYC in all gastric carcinoma cell lines. Furthermore, we demonstrated that gastric adenocarcinoma tissues and AGS cells exhibited abnormal expression of miR-372. Additionally, caudatin downregulated the expression of oncomir miR-372 and miR-21, and upregulated tumor suppressor let-7a miRNA expression. These data revealed that inhibition of Wnt/β-catenin signaling is a novel mechanism of action for caudatin during therapeutic intervention in gastric cancers. IntroductionGastric cancer is one of the most common malignancies and the second leading cause of cancer-related mortality worldwide.Surgery and systemic treatment regimens in combination with radiotherapy and chemotherapy are able to cure this malignancy in the majority of cases. Unfortunately, the young age of typical gastric cancer patients further enhances the time at risk for the side effects of these therapies. Delayed toxicity and the development of secondary malignancies are a serious concern for the current anti-neoplastic armamentarium (1,2). Therefore, it is urgent to further characterize the entity of gastric tumors to better understand and predict their biological behaviors and to identify novel high efficient and low toxic therapeutic agents for the treatment of gastric cancer in clinical practice (3).Modern pharmacologic study proves that C-21 steroidal glycosides are important biological active compounds, which are widely found in the plants of the Asclepiadaceae family and exhibit extensive pharmacological effects such as inhibition of proliferation, induction of apoptosis and inhibition of the invasion of tumor cells (4,5). Caudatin, a C-21 steroidal glycoside, is mainly isolated from the root of Cynanchum bungei Decne in China. Recent studies demonstrated that caudatin induced the apoptosis of HepG2 cells or the SMMC772 cell line (6,7). Wang et al (8) found that caudatin had an inhibitory activity on the secretion of HBsAg and HBV DNA replication. Furthermore, caudatin as a prospective anti-HCC drug with the mechanism...

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Design, synthesis, and molecular hybrids of caudatin and cinnamic acids as novel anti-hepatitis B virus agents

Cited by 39 publications

References 64 publications

Caudatin targets TNFAIP1/NF-κB and cytochrome c/caspase signaling to suppress tumor progression in human uterine cancer

Caudatin targets TNFAIP1/NF-κB and cytochrome c/caspase signaling to suppress tumor progression in human uterine cancer

A Fragmentation Study of Six C₂₁ Steroidal Aglycones by Electrospray Ionization Ion-Trap Time-of-Flight Tandem Mass Spectrometry

Caudatin induces cell apoptosis in gastric cancer cells through modulation of Wnt/β-catenin signaling

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Design, synthesis, and molecular hybrids of caudatin and cinnamic acids as novel anti-hepatitis B virus agents

Cited by 39 publications

References 64 publications

Caudatin targets TNFAIP1/NF-κB and cytochrome c/caspase signaling to suppress tumor progression in human uterine cancer

Caudatin targets TNFAIP1/NF-κB and cytochrome c/caspase signaling to suppress tumor progression in human uterine cancer

A Fragmentation Study of Six C21 Steroidal Aglycones by Electrospray Ionization Ion-Trap Time-of-Flight Tandem Mass Spectrometry

Caudatin induces cell apoptosis in gastric cancer cells through modulation of Wnt/β-catenin signaling

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A Fragmentation Study of Six C₂₁ Steroidal Aglycones by Electrospray Ionization Ion-Trap Time-of-Flight Tandem Mass Spectrometry