Berberine sensitizes nasopharyngeal carcinoma cells to radiation through inhibition of Sp1 and EMT

Abstract

Nasopharyngeal carcinoma (NPC) is a tumor of epithelial origin with radiotherapy as its standard treatment. However, radioresistance remains a critical issue in the treatment of NPC. This study aimed to investigate the effect of berberine on the proliferation, cell cycle regulation, apoptosis, radioresistance of NPC cells and whether specificity protein 1 (Sp1) is a functional target of berberine. Our results showed that treatment with berberine reduced the proliferation and viability of CNE-2 cells in a dose- and time‑dependent manner. Berberine induced cell cycle arrest in the G0/G1 phase and apoptosis. In CNE-2 cells exposed to gamma‑ray irradiation, berberine reduced cell viability at various concentrations (25, 50, 75 and 100 µmol/l). Berberine significantly decreased mRNA and protein expression of Sp1 in the CNE-2 cells. Mithramycin A, a selective Sp1 inhibitor, enhanced the radiosensitivity and the rate of apoptosis in the CNE-2 cells. Berberine inhibited transforming growth factor-β (TGF-β)-induced tumor invasion and suppressed epithelial-to-mesenchymal transition (EMT) process, as evidenced by increased E-cadherin and decreased vimentin proteins. Sp1 may be required for the TGF-β1-induced invasion and EMT by berberine. In conclusion, berberine demonstrated the ability to suppress proliferation, induce cell cycle arrest and apoptosis, and enhance radiosensitivity of the CNE-2 NPC cells. Sp1 may be a target of berberine which is decreased during the radiosensitization of berberine.

Traditional Chinese medicine as a cancer treatment: Modern perspectives of ancient but advanced science

“…Berberine is able to reduce the expression of TGF‐β1, cell migration, and in vivo tumor growth in breast and lung cancer . In nasopharyngeal carcinomas, berberine inhibits TGF‐β‐induced tumor invasion and the EMT process by regulation of E‐cadherin expression and suppression of Sp1 expression . Additionally, berberine attenuates the expression of the cancer stemness marker CD133, upregulates the mesenchymal markers vimentin and fibronectin, and restores the epithelial marker E‐cadherin in neuroblastoma, indicating that berberine can possibly block the cross‐talk between cells undergoing EMT and cancer stem cells, thus inhibiting cancer development and recurrence.…”

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

“…Berberine has diverse pharmacological effects and is normally used for the treatment of gastroenteritis [133,134]. It exhibits significant anti-cancer effects in a wide spectrum of cancers including ovarian, breast, esophageal, and thyroid cancers, leukemia, multiple myeloma, nasopharyngeal carcinoma, and neuroblastoma, through inducing cell cycle arrest and apoptosis, inhibiting metastasis and angiogenesis [135][136][137][138][139][140][141][142][143].…”

Role of metabolism in cancer cell radioresistance and radiosensitization methods

“…It depolymerizes microtubules and prevents HIF1α nuclear accumulation [ 146 ], increasing the radiosensitivity of NPC stem cells and melanoma cells by inactivating NF-κB/HIF1 or HIF1α/PDK1 signaling pathway [ 147 , 148 ]. Berberine can inhibit tumor metastasis, tumorigenicity, and growth, and transforming growth factor-β (TGF-β)-induced tumor invasion and EMT [ 149 ]. Moreover, it enhances the radiosensitivity of NPC cells by inhibiting the expression of HIF1α and VEGF [ 150 ].…”