2. Academic Validation
  3. Targeting Warburg effect: involvement of lactate transporter MCT1 and its chaperone in cancer cell killing by 18β-glycyrrhetinic acid

Targeting Warburg effect: involvement of lactate transporter MCT1 and its chaperone in cancer cell killing by 18β-glycyrrhetinic acid

  • Biochem Biophys Res Commun. 2026 Apr 16:809:153492. doi: 10.1016/j.bbrc.2026.153492.
Bingxin Xia 1,  Chen Zhu 2,  Yi Rao 3
Affiliations

Affiliations

  • 1 Academy for Advanced Interdisciplinary Studies, Department of Chemical Biology, College of Chemistry and Chemical Engineering, School of Pharmaceutical Sciences, Peking-Tsinghua Center for Life Sciences, School of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China.
  • 2 Academy for Advanced Interdisciplinary Studies, Department of Chemical Biology, College of Chemistry and Chemical Engineering, School of Pharmaceutical Sciences, Peking-Tsinghua Center for Life Sciences, School of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China; Chinese Institutes for Medical Research, Capital Medical University, and Chinese Institute for Brain Research, Zhongguanchun Life Sciences Park, Beijing, China.
  • 3 Academy for Advanced Interdisciplinary Studies, Department of Chemical Biology, College of Chemistry and Chemical Engineering, School of Pharmaceutical Sciences, Peking-Tsinghua Center for Life Sciences, School of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China; Chinese Institutes for Medical Research, Capital Medical University, and Chinese Institute for Brain Research, Zhongguanchun Life Sciences Park, Beijing, China. Electronic address: [email protected].
PMID: 41719881 DOI: 10.1016/j.bbrc.2026.153492
Abstract

One of the most commonly used Chinese medicinal herbs is licorice, whose major component is glycyrrizic acid, with a derived product 18β-glycyrrhetinic acid (18β-GA) possessing antitumor activity. Here we performed a genome-wide CRISPR screen to identify genes required for 18β-GA sensitivity. We discovered involvement of MCT1, a lactate transporter, and its membrane chaperone basigin (BSG) in 18β-GA killing of Cancer cells. MCT1 was necessary and sufficient for 18β-GA uptake by Cancer cells. BSG was required for MCT1 localization on the membrane, and hence 18β-GA uptake into and death of, Cancer cells. While it is known that Warburg effects in cancers increased lactate production, followed by selection of higher MCT1 expression which enhanced Cancer cell survival by exporting lactate, our findings reveal a new opportunity for killing Cancer cells by increased 18β-GA sensitivities of Cancer cells with higher MCT1 expression due to the Warburg effect. Thus, our results have revealed a biomarker for 18β-GA sensitivity and suggested the possibility of using Warburg effect to allow drug entry into tumor cells, and will stimulate further molecular mechanistic studies and improvements of traditional Chinese herb medicines.

Keywords

Chinese herb medicine; Transporters; Warburg effect; cancer.

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