Andrographolide inhibits prostate cancer by targeting cell cycle regulators, CXCR3 and CXCR7 chemokine receptors

Mir, Hina; Kapur, Neeraj; Singh, Rajesh; Sonpavde, Guru; Lillard, James W.; Singh, Shailesh

doi:10.1080/15384101.2016.1148836

Cited by 37 publications

(27 citation statements)

References 48 publications

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“…CXCR7 might be a therapeutic target for PCa. Mir et al reported that Andrographolide damages PCa cells via targeting the expression of CXCR3 and CXCR7 [ 27 ], supporting the conclusions of the present study. However, the specific molecular mechanisms by which CXCR7 affects PCa remain unclear and further research is needed.…”

Section: Discussionsupporting

confidence: 91%

Upregulation of CXCR7 Is Associated with Poor Prognosis of Prostate Cancer

et al. 2018

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BackgroundProstate cancer (PCa) is a prevalent cancer in males. CXCR7 exhibits oncogenic actions in various cancers. The aim of our study was to explore the clinical significance of CXCR7 in patients with PCa.Material/MethodsQRT-PCR was used to detect the expression level of CXCR7 in PCa tissues. The relationship between CXCR7 expression and clinicopathologic parameters was evaluated by chi-square test. Kaplan-Meier survival curve was used for the survival analysis of patients. Cox regression analyses were performed to assess the potential of CXCR7 as a prognosis biomarker for PCa patients. We performed MTT and Transwell assays to determine the effect of CXCR7 on proliferative and migratory abilities of PCa cells, respectively.ResultsCXCR7 was upregulated in PCa tissues (P<0.05) and was correlated with PSA (P=0.023), differentiation (P=0.022), and lymph node metastasis (P=0.018). The results of MTT and Transwell assays demonstrated that inhibition of CXCR7 suppressed PCa cells growth and migration. Additionally, high CXCR7 level predicted poor overall survival (log rank test, P=0.019). CXCR7 was a valuable prognostic biomarker for PCa patients (HR=2.271, 95%CI=1.093–4.719, P=0.028).ConclusionsCXCR7 is an oncogene in PCa that can promote aggressive progression of PCa through enhancing proliferation and migration of the tumor cells. CXCR7 is an independent biomarker for the prognosis of PCa.

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Section: Discussionsupporting

confidence: 91%

Upregulation of CXCR7 Is Associated with Poor Prognosis of Prostate Cancer

et al. 2018

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“…Another approach to target NF-κB for cancer therapy is the use of cyclooxygenase-2 (COX-2) inhibitors. Andrographolide (Andro), a diterpenoid lactone extracted from Andrographis paniculata, has been reported to be of therapeutic effect in various cancers showing less adverse effects [139].…”

Section: Cyclooxygenase 2 Inhibitorsmentioning

confidence: 99%

NF-κB and Its Role in Checkpoint Control

Betzler

Theodoraki

Schuler

et al. 2020

IJMS

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Nuclear factor-κB (NF-κB) has been described as one of the most important molecules linking inflammation to cancer. More recently, it has become clear that NF-κB is also involved in the regulation of immune checkpoint expression. Therapeutic approaches targeting immune checkpoint molecules, enabling the immune system to initiate immune responses against tumor cells, constitute a key breakthrough in cancer treatment. This review discusses recent evidence for an association of NF-κB and immune checkpoint expression and examines the therapeutic potential of inhibitors targeting either NF-κB directly or molecules involved in NF-κB regulation in combination with immune checkpoint blockade.

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“… 18 Previous studies have reported that Andro has a role in PCa inhibition through cell cycle regulation. 19 Andro increases the radiation sensitivity of ovarian cancer cells, enhancing apoptosis and autophagy. 20 In this study, we found that Andro significantly improved the sensitivity of PCa cells to TRAIL-induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Andrographolide sensitizes prostate cancer cells to TRAIL-induced apoptosis

Wei

Zhang

2018

Asian J Androl

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising agent for anticancer therapy. The identification of small molecules that can establish the sensitivity of prostate cancer (PCa) cells to TRAIL-induced apoptosis is crucial for the targeted treatment of PCa. PC3, DU145, JAC-1, TsuPr1, and LNCaP cells were treated with Andrographolide (Andro) and TRAIL, and the apoptosis was measured using the Annexin V/PI double staining method. Real time-polymerase chain reaction (PCR) and Western blot analysis were performed to measure the expression levels of target molecules. RNA interference technique was used to down-regulate the expression of the target protein. We established a nude mouse xenograft model of PCa, which was used to measure the caspase-3 activity in the tumor cells using flow cytometry. In this research study, our results demonstrated that Andro preferentially increased the sensitivity of PCa cells to TRAIL-induced apoptosis at subtoxic concentrations, and the regulation mechanism was related to the up-regulation of DR4. In addition, it also increased the p53 expression and led to the generation of reactive oxygen species (ROS) in the cells. Further research revealed that the DR4 inhibition, p53 expression, and ROS generation can significantly reduce the apoptosis induced by the combination of TRAIL and Andro in PCa cells. In conclusion, Andro increases the sensitivity of PCa cells to TRAIL-induced apoptosis through the generation of ROS and up-regulation of p53 and then promotes PCa cell apoptosis associated with the activation of DR4.

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Andrographolide inhibits prostate cancer by targeting cell cycle regulators, CXCR3 and CXCR7 chemokine receptors

Cited by 37 publications

References 48 publications

Upregulation of CXCR7 Is Associated with Poor Prognosis of Prostate Cancer

Upregulation of CXCR7 Is Associated with Poor Prognosis of Prostate Cancer

NF-κB and Its Role in Checkpoint Control

Andrographolide sensitizes prostate cancer cells to TRAIL-induced apoptosis

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