Inhibition of Nrf2 promotes the antitumor effect of Pinelliae rhizome in papillary thyroid cancer

Abstract

We previously reported that Xiaotan Sanjie (XTSJ) decoction can prevent the progression of gastric cancer in vitro and in vivo. Pinelliae rhizome (PR), one component of XTSJ decoction, has an inhibitory effect on the growth and proliferation of tumor cells. The present study investigated the underlying mechanisms of action of PR. Using the human papillary thyroid cancer cell lines, TPC‐1 and BCPAP, we found that XTSJ decoction and PR alone decreased cell viability to a similar extent in both cell lines, whereas treatment with XTJS decoction without PR [PR (−)] had a lesser effect. PR treatment inhibited the expression of nuclear factor erythroid 2‐related factor 2 (Nrf2) in a dose‐dependent manner. To investigate the role of Nrf2 in the PR‐mediated effects of XTSJ, knockdown of Nrf2 in the tumor cell lines using Nrf2 siRNA (siNrf2) was performed and transfected cells were treated with PR. Silencing of Nrf2 amplified the effects on autophagy, cell viability, apoptosis, and colony formation. Similar results were obtained following treatment with the autophagy inhibitor 3‐methyladenine (3‐MA). Furthermore, treatment with PR, siNrf2, and/or 3‐MA inhibited the MAPK pathway, and analysis of the MAPK pathway components confirmed the role of this pathway in the PR‐mediated cellular effects. In mice implanted with siNrf2‐transfected cells, the effects of PR were amplified. Taken together, these findings indicate that PR is critical for the inhibitory effects of XTSJ decoction on tumor cell viability and that downregulation of Nrf2 promotes the antitumor effects of PR on papillary thyroid cancer cells.

Combined lead and zinc oxide‐nanoparticles induced thyroid toxicity through 8‐OHdG oxidative stress‐mediated inflammation, apoptosis, and Nrf2 activation in rats

“…The nuclear Nrf2 accumulates and binds with antioxidant reaction pieces promoting cytoprotective gene transcriptions involving antioxidant, antitoxic, and anti-inflammatory actions. 78 Nrf2 plays an important role in the thyroid gland, it promotes the transcription and protein synthesis of antioxidant and cytoprotective molecules. It protects against intra-thyroidal oxidative damage and prevent excessive iodination.…”

The Keap1/Nrf2 Signaling Pathway in the Thyroid—2020 Update

“…In mice orthotopically transplanted with a PTC cell line, the combination of Nrf2 knockdown in the PTC cells before transplantation and PR treatment of the animals significantly decreased the tumor burden and extended the survival of the animals. In contrast, when the PTC cells were transplanted into the thyroids of Nrf2 KO mice, the tumor burden was increased, survival was shortened, and the protective effect of PR treatment was lost [70]. Taken together, the findings of the aforementioned recent studies further support the original concept that the Nrf2 pathway is activated in PTC and has a protective effect in thyroid carcinoma cells [63].…”

“…In two PTC cell lines, knockdown of LUCAT1 decreased Nrf2 mRNA expression levels and Nrf2 protein abundance, while at the same time it reduced cell proliferation and invasion, and induced cell-cycle arrest and apoptosis [69]. Lastly, another study showed that Pinelliae rhizome (PR), a component of a traditional medicine decoction, decreased the protein abundance of Nrf2 in the nucleus of PTC cell lines in a dose-dependent manner, and decreased their viability [70]. Knockdown of Nrf2 via small interfering RNA (siRNA) in the PTC cell lines decreased their viability and had an additive or synergistic effect with PR.…”

Potential Mechanisms for Traditional Chinese Medicine in Treating Airway Mucus Hypersecretion Associated With Coronavirus Disease 2019

“…Pinellia ternata Eliminating phlegm, inhibiting the secretion of gastric juice, increasing the activity of tyrosine transaminase, promoting bile secretion, antivomiting, and antitumor effect (Du et al, 2019) Citri Reticulatae Pericarpium…”