Andrographolide sensitizes Hep-2 human laryngeal cancer cells to carboplatin-induced apoptosis by increasing reactive oxygen species levels

Andrographolide is a natural diterpenoid from Andrographis paniculata that has been proposed as an anticancer agent as well as a chemosensitizer for use in combination with anticancer drugs. Carboplatin is the first-line chemotherapeutic agent for advanced laryngeal carcinoma. However, the clinical efficacy of carboplatin is limited by drug resistance and side effects. The aim of this study was to investigate whether andrographolide has a synergistic antitumor effect with carboplatin on human laryngeal cancer cells. Hep-2 cells were exposed to andrographolide with or without carboplatin. The effects of indicated therapies were examined using the Cell Counting Kit-8 assay, the colony-forming assay, the Hoechst 33342/PI double staining, and flow cytometry analysis. The molecular mechanism was assessed by reactive oxygen species (ROS) detection and western blot. At the sublethal concentration, andrographolide increased carboplatin sensitivity of Hep-2 cells by increasing carboplatin-induced apoptosis and inhibiting cell viability. Moreover, we found that andrographolide sensitized carboplatin mainly through the induction of ROS generation and apoptotic signaling. Taken together, these results indicate that andrographolide, along with carboplatin, synergistically inhibited cell proliferation and induced mitochondrial apoptosis of Hep-2 cells by increasing the intracellular ROS, regulating the mitogen-activated protein kinase and phosphatidylinositol 3-kinase (PI3K/AKT) pathways, altering the BCL2/BAX ratio, and ultimately activating the cleavage of Caspase-3 and PARP. These results suggest that andrographolide sensitizes human laryngeal cancer cells to carboplatin-induced apoptosis by increasing ROS levels. *Wenjing Mao and Peijie He contributed equally to the writing of this article. Correspondence to Chunsheng Wei, PhD, Department of Otolaryngology-Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Affiliated Eye, Ear, Nose and Throat Hospital, Fudan University, No. 83, Fenyang Road, Shanghai 200031, China Tel/fax: +86 21 6437 7134; e-mail: weics2003@163.com Received October 2, 2018 Accepted February 7, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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