Ascorbate-induced oxidative stress mediates TRP channel activation and cytotoxicity in human etoposide-sensitive and -resistant retinoblastoma cells.

ABSTRACT: There are indications that pharmacological doses of ascorbate (Asc) used as an adjuvant improve the chemotherapeutic management of cancer. This favorable outcome stems from its cytotoxic effects due to prooxidative mechanisms. Since regulation of intracellular Ca²⁺ levels contributes to the maintenance of cell viability, we hypothesized that one of the effects of Asc includes disrupting regulation of intracellular Ca²⁺ homeostasis. Accordingly, we determined if Asc induced intracellular Ca²⁺ influx through activation of pertussis sensitive Gi/o-coupled GPCR which in turn activated transient receptor potential (TRP) channels in both etoposide-resistant and -sensitive retinoblastoma (WERI-Rb1) tumor cells. Ca²⁺ imaging, whole-cell patch-clamping, a

SUBMITTER: Oronowicz J 

PROVIDER: S-EPMC7758186 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature