2. Academic Validation
  3. Chemoproteomic Identification of ALDOA as the Glycolytic Target of α-Cembratriene-4,6-diol in Lung Cancer Cells

Chemoproteomic Identification of ALDOA as the Glycolytic Target of α-Cembratriene-4,6-diol in Lung Cancer Cells

  • J Agric Food Chem. 2026 Mar 11;74(9):7652-7662. doi: 10.1021/acs.jafc.5c17305.
Zhonghao Sun 1 2,  Pingping Liu 1,  Guoxu Ma 2,  Xinyao Li 2,  Mingzhen Liu 2,  Qiansi Chen 1,  Guoyun Xu 1,  Niu Zhai 1,  Hui Zhang 1,  Lifeng Jin 1,  Huina Zhou 1,  Qingxia Zheng 1
Affiliations

Affiliations

  • 1 Zhengzhou Tobacco Research Institute of CNTC, Zhengzhou, Henan 450001, PR China.
  • 2 Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.
PMID: 41766208 DOI: 10.1021/acs.jafc.5c17305
Abstract

Tobacco (Nicotiana tabacum L.) is a globally important economic crop and a rich source of bioactive cembratriene-4,6-diol (CBT-diol). The unique macrocyclic scaffold of these compounds has prompted an extensive study of its bioactivity. Although CBT-diol has known antitumor activity, its specific molecular targets remain unclear, hindering the translational development of tobacco-based therapeutics. In this study, we identified ALDOA as the direct target of tobacco-derived α-CBT-diol against A549 lung Cancer cells. Using activity-based proteomics and target validation methods, we show that α-CBT-diol binds to the ALDOA catalytic site with high affinity (Kd = 12.4 μM) and inhibits its activity. Definitively, studies in ALDOA-knockout cells confirmed that α-CBT-diol inhibits ALDOA activity, thereby suppressing tumor glycolysis and growth by reducing glucose uptake and lactate production. To the best of our knowledge, α-CBT-diol represents the first identified member of the tobacco cembranoid class that exerts antitumor effects by targeting ALDOA.

Keywords

6-diol; ABPP; ALDOA; target identification; tobacco; α-cembratriene-4.

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