Synergy of Raddeanin A and cisplatin induced therapeutic effect enhancement in human hepatocellular carcinoma

Li, Jiannan; Yu, Yao; Zhang, Yanfei; Li, Zhimeng; Cai, Guangzhi; Gong, Jiyu

doi:10.1016/j.bbrc.2017.02.079

Cited by 24 publications

(19 citation statements)

References 22 publications

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“…Raddeanin A (RA) is an active oleanane-type triterpenoid saponin extracted from a commonly used traditional Chinese medicinal herb, Anemone raddeana Regel, which exerts antitumor activity through inhibiting proliferation and angiogenesis and inducing apoptosis in multiple cancer cell types, such as human colorectal cells, gastric cancer cells, and human hepatocellular carcinoma cells. [4][5][6][7] RA mainly functions to reduce inflammation and tumor activity. Furthermore, recent research has shown that RA can suppress the progression of human colorectal carcinoma.…”

Section: Introductionmentioning

confidence: 99%

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Antitumor activity of Raddeanin A is mediated by Jun amino‐terminal kinase activation and signal transducer and activator of transcription 3 inhibition in human osteosarcoma

et al. 2019

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Osteosarcoma is the most common primary malignant bone tumor. Raddeanin A ( RA ) is an active oleanane‐type triterpenoid saponin extracted from the traditional Chinese herb Anemone raddeana Regel that exerts antitumor activity against several cancer types. However, the effect of RA on osteosarcoma remains unclear. In the present study, we showed that RA inhibited proliferation and induced apoptosis of osteosarcoma cells in a dose‐ and time‐dependent way in vitro and in vivo. RA treatment resulted in excessive reactive oxygen species ( ROS ) generation and JNK and ERK 1/2 activation. Apoptosis induction was evaluated by the activation of caspase‐3, caspase‐8, and caspase‐9 and poly‐ADP ribose polymerase ( PARP ) cleavage. RA ‐induced cell death was significantly restored by the ROS scavenger glutathione ( GSH ), the pharmacological inhibitor of JNK SP 600125, or specific JNK knockdown by sh RNA . Additionally, signal transducer and activator of transcription 3 ( STAT 3) activation was suppressed by RA in human osteosarcoma, and this suppression was restored by GSH , SP 600125, and JNK ‐sh RNA . Further investigation showed that STAT 3 phosphorylation was increased after JNK knockdown. In a tibial xenograft tumor model, RA induced osteosarcoma apoptosis and notably inhibited tumor growth. Taken together, our results show that RA suppresses proliferation and induces apoptosis by modulating the JNK /c‐Jun and STAT 3 signaling pathways in human osteosarcoma. Therefore, RA may be a promising candidate antitumor drug for osteosarcoma intervention.

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Section: Introductionmentioning

confidence: 99%

“…Furthermore, recent research has shown that RA can suppress the progression of human colorectal carcinoma. [4][5][6][7] However, the effects of RA on human osteosarcoma cells are unknown.…”

Section: Introductionmentioning

confidence: 99%

Antitumor activity of Raddeanin A is mediated by Jun amino‐terminal kinase activation and signal transducer and activator of transcription 3 inhibition in human osteosarcoma

et al. 2019

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“…And in our preliminary studies, RA can suppress choriocarcinoma JEG‐3 cells proliferation (unpublished data). More importantly, RA showed synergy with cisplatin in therapeutic effect in human hepatocellular carcinoma (Li et al, ). However, its effect and mechanisms on drug resistance are still largely unknown.…”

Section: Introductionmentioning

confidence: 99%

The STAT3/NFIL3 signaling axis‐mediated chemotherapy resistance is reversed by Raddeanin A via inducing apoptosis in choriocarcinoma cells

Zheng

Zhang

Zhou

et al. 2018

Journal Cellular Physiology

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Chemotherapy resistance is the major issue of choriocarcinoma. Apoptosis always is the ultimate outcome of chemotherapeutic drugs, which considered one of the reasons of resistance. We investigated the role of STAT3/NFIL3 signaling‐inhibited apoptosis in chemotherapy resistance and whether Raddeanin A (RA) could be a new drug to reverse resistance. Established three drug‐resistant cell lines as JEG‐3/MTX, JEG‐3/5‐FU, and JEG‐3/VP16. NFIL3 and STAT3 expression was evaluated in the cells. The IC50 value, apoptosis rate and apoptins were observed with transfection of siNFIL3, Lenti‐OE™‐NFIL3, shSTAT3, and Lenti‐OE™‐STAT3 or RA treatment. In addition, the luciferase reporter analysis and co‐immunoprecipitation assays were used to investigate the relation of STAT3 and NFIL3. Hyper‐activation of STAT3 and NFIL3 expression were observed in three drug‐resistant cell lines. STAT3 enhanced NFIL3 transcriptional activity by binding the relative promoter region. Activated STAT3/NFIL3 pathway caused low rate of apoptosis which resulted in chemotherapy resistance. RA reduced the resistance index of resistant cells and induced caspase 3 dependent apoptosis, meanwhile it repressed the STAT3/NFIL3 activation. STAT3/NFIL3 axis‐inhibited apoptosis is a novel mechanism of chemotherapy resistance in choriocarcinoma. With the suppression of STAT3/NFIL3 axis and apoptosis induction, RA is a potential agent or lead candidate for improving chemotherapy.

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“…Nonetheless, several reports have demonstrated that excessive accumulation of intracellular ROS is usually associated with apoptosis in cancer cells [41,42]. Li et al showed that RA exerted a synergistic effect with cisplatin on inducing ROS production in hepatocellular carcinoma [43]. Liu et al reported that oxidative stress occurred after exposure to a concentration of 300 μM H 2 O 2 and caspase-3-involved apoptosis was detected in the human glioma U251 cell line [44].…”

Section: Figurementioning

confidence: 99%

Raddeanin a Suppresses Glioblastoma Growth by Inducing ROS Generation and Subsequent JNK Activation to Promote Cell Apoptosis

Peng

Wang

Shu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Raddeanin A (RA), an active pharmacological ingredient from Anemone raddeana Regel, plays an important role in tumor suppression. In this study, we assessed the potentially therapeutic effect of RA on glioblastoma and its underlying mechanisms. Methods: Cell viability was examined using the MTT assay. Invasive and migratory capacities were examined using Transwell and wound healing assays. Apoptosis was determined by Hoechst staining, flow cytometry, DCFH-fluorescent probe and immunohistochemical staining. Autophagy was detected by transmission electron microscopy and western blotting. A U251 glioma xenograft model was established to evaluate the effect of RA in vivo. Results: The data demonstrated that RA inhibited viability, and abrogated the invasive/migratory abilities of glioblastoma cells. In addition, RA induced apoptosis by reactive oxygen species (ROS)/ Jun N-terminal kinase (JNK) signaling in glioblastoma. Conversely, the antioxidant N-Acetyl-L-cysteine (NAC) and pan-caspase inhibitor z-VAD-fmk attenuated RA-induced apoptosis by scavenging ROS and inactivating caspase-3. Furthermore, the inhibition of autophagy by 3-MA exacerbated apoptosis through ROS generation and JNK phosphorylation. In vivo, RA exhibited a curative effect on U251-derived xenografts in nude mice. Conclusions: The results of this study suggest that RA suppressed the growth of glioblastoma, thus serving as a promising and potential strategy for glioblastoma chemotherapy.

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Synergy of Raddeanin A and cisplatin induced therapeutic effect enhancement in human hepatocellular carcinoma

Cited by 24 publications

References 22 publications

Antitumor activity of Raddeanin A is mediated by Jun amino‐terminal kinase activation and signal transducer and activator of transcription 3 inhibition in human osteosarcoma

Antitumor activity of Raddeanin A is mediated by Jun amino‐terminal kinase activation and signal transducer and activator of transcription 3 inhibition in human osteosarcoma

The STAT3/NFIL3 signaling axis‐mediated chemotherapy resistance is reversed by Raddeanin A via inducing apoptosis in choriocarcinoma cells

Raddeanin a Suppresses Glioblastoma Growth by Inducing ROS Generation and Subsequent JNK Activation to Promote Cell Apoptosis

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