Raddeanin A down‐regulates androgen receptor and its splice variants in prostate cancer

Xia, Haijian; Hu, Cheng; Bai, Shanshan; Lyu, Jing; Zhang, Bryan Y.; Yu, Xianghui; Yang, Zhan; Zhao, Lijing; Dong, Yan

doi:10.1111/jcmm.14267

Cited by 9 publications

(13 citation statements)

References 56 publications

(128 reference statements)

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“…Due to the side effects of chemotherapy and radiography, the use of traditional Chinese medicine has become widely accepted as an effective method to treat cancers. Being an oleanane-type triterpenoid saponin extracted from the root of Anemone raddeana Regel, RA displays a promising anti-tumor effect on malignant tumors, including endometrial cancer and prostate cancer [ 25 , 26 ]. Compelling evidence indicates that RA inhibits the invasion, migration, adhesion and induces apoptosis of human gastric cancer cells, exhibiting potential to become an antitumor drug [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Raddeanin A inhibits proliferation, invasion, migration and promotes apoptosis of cervical cancer cells via regulating miR-224-3p/Slit2/Robo1 signaling pathway

Shen¹,

et al. 2021

Aging

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Raddeanin A (RA), an active triterpenoid saponin extracted from the Anemone raddeana regel, plays an essential role in the suppression of many malignancies. We aimed to investigate the effects and potential mechanisms of RA on cervical cancer (CC). RA was used to treat CC cell lines (Hela and c-33A) for 24 h and 48 h. Then, the invasion, migration and cell cycle distribution of these two cell lines with RA treatment were respectively detected by transwell, wound healing and flow cytometry. Results revealed that RA significantly inhibited the invasion, migration, promoted the cell cycle arrest and apoptosis of Hela and c-33A cells. Moreover, RA was confirmed to activate the Slit2/Robo1 signaling, and bioinformatics analysis and luciferase reporter assay verified that miR-224-3p could target Slit2. Additionally, miR-224-3p overexpression reversed the inhibitory effect of RA on invasion and migration of CC cells, and it also restored the promoting effects of RA on cell cycle arrest and apoptosis. Lastly, miR-224-3p-upregulation inactivated the expression of Slit2 and Robo1 in RA-treated Hela and c-33A cells. These findings demonstrated that RA inhibits proliferation, invasion, migration and promotes apoptosis of CC cells through miR-224-3p/Slit2/Robo1 signaling pathway, which might guide the future studies or treatment of this disease.

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Section: Discussionmentioning

confidence: 99%

Raddeanin A inhibits proliferation, invasion, migration and promotes apoptosis of cervical cancer cells via regulating miR-224-3p/Slit2/Robo1 signaling pathway

Shen¹,

et al. 2021

Aging

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“…It promotes proteasome-mediated degradation and inhibition of androgen receptor (AR) gene transcription. It has been reported to promote the growth-inhibitory effect of docetaxel, a drug used in prostate cancer chemotherapy (17). Bone metastasis is a serious complication of advanced breast cancer, resulting in osteolysis and increased mortality.…”

Section: Discussionmentioning

confidence: 99%

Raddeanin A suppresses lung cancer cell proliferation via induction of apoptosis and increased production of ROS

Jin

Xiao-lin

et al. 2020

Cell Mol Biol (Noisy-le-grand)

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At present, in vitro cell experiments have confirmed that RaddeaninA can effectively inhibit the proliferation of some tumor cells, but the effect of RaddeaninA on lung cancer cells has not been observed. Therefore, this study explored its effect on lung cancer cells and its mechanism of action. Human lung cancer cell lines were treated with serum-free medium and varied concentrations of Raddeanin A. Cell proliferation and apoptosis were determined using MTT, and flow cytometric assays, respectively. The intracellular level of ROS was determined using DCFH-DA assay. Protein and mRNA expressions of bax, bcl-2 and cyt c were measured using Western blotting and qRT-PCR. RaddeaninA treatment can promote PC-9 cell apoptosis in a time and dose-dependent manner (p<0.05).Treatment of PC-9 cells with Raddeanin significantly and dose-dependently increased the activities of caspase-9 and caspase-3 (p<0.05), and led to significant and dose-dependent increases in ROS levels (p<0.05). Treatment of PC-9 cells with Raddeanin A led to significant and dose-dependent decreases in mitochondrial membrane potential (p<0.05). It significantly and dose-dependently upregulated bax mRNA and protein expressions, but down-regulated bcl-2 mRNA and protein expressions significantly and dose-dependently (p<0.05). On the other hand, Raddeanin significantly and dose-dependently down-regulated cytoplasmic bax protein expression, while upregulating cyt c expression (p<0.05). Similarly, bax protein expression was significantly and dose-dependently upregulated in mitochondria, but the corresponding cyt c expression was significantly and dose-dependently down-regulated (p<0.05). Raddeanin A is a potential and effective lung cancer chemotherapy drug, which can induce lung cancer cell apoptosis and inhibit proliferation.

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“…5-FU is the most common chemotherapeutic compound for cancer treatment [69]. RA sensitized cholangiocarcinoma cell lines to 5-FU treatment and ameliorated 5-FU resistance in bile duct cancer cells through activating multiple cell cycle and apoptosis-related factors, such as COX-2, Bax, Bcl-2, and cyclins E/D1 [136]. RA may also have the potential to enhance the growth inhibitory efficacy of docetaxel, the first-line chemotherapy for prostate cancer [137].…”

Section: Chemosensitizing Properties Of Ramentioning

confidence: 99%

“…RA may also have the potential to enhance the growth inhibitory efficacy of docetaxel, the first-line chemotherapy for prostate cancer [137]. The growth and survival of prostate cancer cells rely on androgen receptor (AR) [136]. Splice variants of AR (AR-V) expression have been proposed to be a mechanism of docetaxel resistance.…”

Section: Chemosensitizing Properties Of Ramentioning

confidence: 99%

Anticancer Potential of Raddeanin A, a Natural Triterpenoid Isolated from Anemone raddeana Regel

et al. 2020

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Natural compounds extracted from plants have gained immense importance in the fight against cancer cells due to their lesser toxicity and potential therapeutic effects. Raddeanin A (RA), an oleanane type triterpenoid is a major compound isolated from Anemone raddeana Regel. As an anticancer agent, RA induces apoptosis, cell cycle arrest, inhibits invasion, migration and angiogenesis in malignant cell lines as well as in preclinical models. In this systemic review, the pharmacological effects of RA and its underlying molecular mechanisms were carefully analyzed and potential molecular targets have been highlighted. The apoptotic potential of RA can be mediated through the modulation of Bcl-2, Bax, caspase-3, caspase-8, caspase-9, cytochrome c and poly-ADP ribose polymerase (PARP) cleavage. PI3K/Akt signaling pathway serves as the major molecular target affected by RA. Furthermore, RA can block cell proliferation through inhibition of canonical Wnt/β-catenin signaling pathway in colorectal cancer cells. RA can also alter the activation of NF-κB and STAT3 signaling pathways to suppress invasion and metastasis. RA has also exhibited promising anticancer potential against drug resistant cancer cells and can enhance the anticancer effects of several chemotherapeutic agents. Overall, RA may function as a promising compound in combating cancer, although further in-depth study is required under clinical settings to validate its efficacy in cancer patients.

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Raddeanin A down‐regulates androgen receptor and its splice variants in prostate cancer

Cited by 9 publications

References 56 publications

Raddeanin A inhibits proliferation, invasion, migration and promotes apoptosis of cervical cancer cells via regulating miR-224-3p/Slit2/Robo1 signaling pathway

Raddeanin A inhibits proliferation, invasion, migration and promotes apoptosis of cervical cancer cells via regulating miR-224-3p/Slit2/Robo1 signaling pathway

Raddeanin A suppresses lung cancer cell proliferation via induction of apoptosis and increased production of ROS

Anticancer Potential of Raddeanin A, a Natural Triterpenoid Isolated from Anemone raddeana Regel

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