Are NHE1 and inducible nitric oxide synthase involved in human ovarian cancer?

Sanhueza, Carlos; Araos, Joaquín; Naranjo, L.; Barros, Eric; Toledo, Lilian; Subiabre, Mario; Toledo, Fernando; Gutiérrez, Jaime; Chiarello, Delia I.; Pardo, Fabián; Leiva, Andrea; Sobrevía, Luis

doi:10.1016/j.phrs.2016.01.007

Cited by 5 publications

(1 citation statement)

References 16 publications

(28 reference statements)

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“…NHE1 can facilitate the EMT progress and contribute to invasion and metastasis [21][22][23]. In consistent, elevated expression of NHE1 was observed in many types of cancers, including breast cancer [21], gastric cancer [23] and ovarian cancer [24]. Since SK can inhibit aerobic glycolysis, it is rational that SK may has regulatory effect on NHE1 expression, and subsequently effluence the EMT in cancer cells.…”

Section: Introductionmentioning

confidence: 93%

Shikonin suppresses the epithelial-to-mesenchymal transition by downregulating NHE1 in bladder cancer cells

Jia

et al. 2021

J. Cancer

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Shikonin (SK) is the major bioactive component extracted from the roots of Lithospermum erythrorhizon with anticancer activity. SK could inhibit the epithelial-to-mesenchymal transition (EMT) of cancer cells. However, the underlying mechanism is elusive. In the present study, the inhibitory activities of SK on proliferation, invasion and migration were examined in bladder cancer (BC) cells. SK potently decreased the viabilities of BC cells but showed less cytotoxicity to normal bladder epithelial cells. Moreover, SK reversed the EMT, suppressed the migration and invasion of BC cells. Intriguingly, NHE1, the major proton efflux pump, was dramatically down-regulated by SK. The EMT-inhibitory effect of SK was mediated by NHE1 down-regulation, as NHE1-overexpress alleviated while Cariporide (NHE1 inhibitor) enhanced this effect. Further, enforced alkalinization of intracellular pH (pHi) reversed the EMT-inhibitory effect of SK, indicating a key role of acidic pHi in this process. Finally, elevated NHE1 expression was observed in human bladder cancer tissues. Collectively, this research reveals a supportive effect of NHE1 and alkaline pHi on EMT. SK can suppress EMT through inhibiting NHE1 and hence inducing an acidic pHi.

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