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Peer-reviewedCC BY 4.0Frontiers in Pharmacology

Thymoquinone suppresses papillary thyroid carcinoma by impairing autophagic flux via the PDZK1IP1/HMGCS1 axis

  • Hanyang Lin1
  • Ziqi Yan1
  • Yuhan Shi2
  • Zhaoyue Zhou3
  • Qingxin Song1
  • Xuanlu Zhang4
  • Yuan Shao1
  • Wei Liu5
  • Bo Kou1
5 affiliations
  1. 1Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Xi’an Jiaotong University
  2. 2Shaanxi Provincial People’s Hospital
  3. 3Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center
  4. 4Department of Thyroid, Breast and Vascular Surgery, The First Affiliated Hospital of Air Force Medical University (Xijing Hospital)
  5. 5Department of Vascular Surgery, The First Affiliated Hospital of Xi’an Jiaotong University
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Abstract

Background and Aim: Thymoquinone (TQ), the principal bioactive constituent of Nigella sativa , has antitumor activity in multiple malignancies, but its mechanism in papillary thyroid carcinoma (PTC) remains incompletely defined.

Experimental Procedure: We evaluated the effects of TQ on PTC cell proliferation, apoptosis, autophagic flux, and tumor growth, and examined the PDZK1IP1/HMGCS1 axis.

Key Results: TQ reduced viability and clonogenic growth in TPC-1 and BCPAP cells, increased apoptosis, downregulated PCNA and Bcl-2, and upregulated cleaved caspase-3, cleaved PARP, and BAX. TQ also increased autophagy-related vesicles and p62 and LC3-II levels. Tandem mRFP-GFP-LC3B reporter imaging showed accumulation of both yellow dual-positive and red-only LC3 puncta. Together with pharmacological modulation using bafilomycin A1, chloroquine, and rapamycin, these findings supported impaired late-stage autophagic processing. Integrated public PTC datasets and TQ-treated TPC-1 RNA-seq data identified PDZK1IP1 as a candidate mediator. PDZK1IP1 knockdown enhanced, whereas overexpression attenuated, TQ-induced proliferation inhibition, apoptosis, and autophagy-marker accumulation. HMGCS1 was identified as a downstream effector; its overexpression partially rescued these effects in both TPC-1 and BCPAP cells. In xenografts, TQ suppressed tumor growth, reduced Ki67, PDZK1IP1, and HMGCS1, and increased LC3 and p62.

Conclusion and Implications: TQ suppresses PTC progression by impairing autophagic flux and downregulating PDZK1IP1/HMGCS1.

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Cite

BibTeXRIS
BibTeX
@article{lin2026thymoquinone,
  title = {{Thymoquinone suppresses papillary thyroid carcinoma by impairing autophagic flux via the PDZK1IP1/HMGCS1 axis}},
  author = {Hanyang Lin and Ziqi Yan and Yuhan Shi and Zhaoyue Zhou and Qingxin Song and Xuanlu Zhang and Yuan Shao and Wei Liu and Bo Kou},
  journal = {Frontiers in Pharmacology},
  year = {2026},
  month = oct,
  doi = {10.3389/fphar.2026.1966917},
  url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1966917/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Thymoquinone suppresses papillary thyroid carcinoma by impairing autophagic flux via the PDZK1IP1/HMGCS1 axis
AU  - Hanyang Lin
AU  - Ziqi Yan
AU  - Yuhan Shi
AU  - Zhaoyue Zhou
AU  - Qingxin Song
AU  - Xuanlu Zhang
AU  - Yuan Shao
AU  - Wei Liu
AU  - Bo Kou
PY  - 2026
DA  - 2026/10/26
JO  - Frontiers in Pharmacology
DO  - 10.3389/fphar.2026.1966917
UR  - https://www.frontiersin.org/articles/10.3389/fphar.2026.1966917/full
AB  - Background and Aim: Thymoquinone (TQ), the principal bioactive constituent of Nigella sativa , has antitumor activity in multiple malignancies, but its mechanism in papillary thyroid carcinoma (PTC) remains incompletely defined.  Experimental Procedure: We evaluated the effects of TQ on PTC cell proliferation, apoptosis, autophagic flux, and tumor growth, and examined the PDZK1IP1/HMGCS1 axis.  Key Results: TQ reduced viability and clonogenic growth in TPC-1 and BCPAP cells, increased apoptosis, downregulated PCNA and Bcl-2, and upregulated cleaved caspase-3, cleaved PARP, and BAX. TQ also increased autophagy-related vesicles and p62 and LC3-II levels. Tandem mRFP-GFP-LC3B reporter imaging showed accumulation of both yellow dual-positive and red-only LC3 puncta. Together with pharmacological modulation using bafilomycin A1, chloroquine, and rapamycin, these findings supported impaired late-stage autophagic processing. Integrated public PTC datasets and TQ-treated TPC-1 RNA-seq data identified PDZK1IP1 as a candidate mediator. PDZK1IP1 knockdown enhanced, whereas overexpression attenuated, TQ-induced proliferation inhibition, apoptosis, and autophagy-marker accumulation. HMGCS1 was identified as a downstream effector; its overexpression partially rescued these effects in both TPC-1 and BCPAP cells. In xenografts, TQ suppressed tumor growth, reduced Ki67, PDZK1IP1, and HMGCS1, and increased LC3 and p62.  Conclusion and Implications: TQ suppresses PTC progression by impairing autophagic flux and downregulating PDZK1IP1/HMGCS1.
SN  - 1663-9812
ER  -