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Ramulus Mori alkaloids (SZ-A) sensitize triple-negative breast cancer to cisplatin via PLA2G2A-mediated ceramide metabolism
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Chao Chen1, 2, Mengqi Wan1, 2, Zhixu Zhu1, 2, Zhaoyu Xie1, 2, Yu Zhang1, 2, Tao Xu1, 2, Han Meng1, 2, Miaomiao Wu1, 2, Liangfeng Gui1, 2, Hongbo Lv1, 2, Guodong Wang1, 2, *, Jun Han3, *, Hui Che1, 3, 4, *
Chinese Journal of Natural Medicines | 2026, 24(8) : 972 - 986
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Chinese Journal of Natural Medicines | 2026, 24(8): 972-986
• Original Article •
Ramulus Mori alkaloids (SZ-A) sensitize triple-negative breast cancer to cisplatin via PLA2G2A-mediated ceramide metabolism
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Chao Chen1, 2, Mengqi Wan1, 2, Zhixu Zhu1, 2, Zhaoyu Xie1, 2, Yu Zhang1, 2, Tao Xu1, 2, Han Meng1, 2, Miaomiao Wu1, 2, Liangfeng Gui1, 2, Hongbo Lv1, 2, Guodong Wang1, 2, *, Jun Han3, *, Hui Che1, 3, 4, *
Affiliations
  • 1Department of Pharmacology, Wannan Medical College, Wuhu 241002, China
  • 2Anhui Innovative Center for Drug Basic Research of Metabolic Diseases, Wannan Medical College, Wuhu 241002, China
  • 3Wuhu Modern Technology Research and Development Center of Chinese Herbal Medicine and Functional Food, Anhui College of Traditional Chinese Medicine, Wuhu 241002, China
  • 4Department of Endocrinology and Genetic Metabolism, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu 241002, China
About Author:

∆

These authors contributed equally to this work.

Published: 2026-08-20 doi: 10.1016/S1875-5364(26)61196-X
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Cisplatin (DDP) remains a standard therapy for triple-negative breast cancer (TNBC), yet intrinsic or acquired resistance often limits its efficacy; here, we report that Ramulus Mori alkaloids (SZ-A), an approved botanical α-glucosidase inhibitors, synergize with DDP to suppress TNBC progression in vitro and in vivo by driving PLA2G2A-dependent ceramide accumulation. Combining SZ-A with DDP synergistically inhibits viability, clonogenicity, migration, and invasion, induces S-phase arrest and apoptosis, and attenuates tumor growth in xenograft models. Mechanistically, SZ-A directly binds to and stabilizes PLA2G2A, blocking its autophagic-lysosomal degradation, leading to accumulated PLA2G2A that suppresses fatty acid oxidation and triggers ceramide accrual via ADIPOR2 inhibition. Genetic ablation of PLA2G2A abrogates these effects. DDP further enhances SZ-A-induced PLA2G2A upregulation and ceramide accumulation, resulting amplified cytotoxicity. Our findings reveal SZ-A as a chemosensitizing agent that enhances the efficacy of DDP in TNBC.

Ramulus Mori alkaloids  /  Triple-negative breast cancer (TNBC)  /  Cisplatin  /  Phospholipase A2 Group IIA (PLA2G2A)  /  Ceramide
Chao Chen, Mengqi Wan, Zhixu Zhu, Zhaoyu Xie, Yu Zhang, Tao Xu, Han Meng, Miaomiao Wu, Liangfeng Gui, Hongbo Lv, Guodong Wang, Jun Han, Hui Che. Ramulus Mori alkaloids (SZ-A) sensitize triple-negative breast cancer to cisplatin via PLA2G2A-mediated ceramide metabolism[J]. Chinese Journal of Natural Medicines, 2026 , 24 (8) : 972 -986 . DOI: 10.1016/S1875-5364(26)61196-X
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  • National Natural Science Foundation of China(82270879; 82504844)
  • Foundation of Excellent Youth Scholars of Education Committee of Anhui Province of China(2022AH030124)
  • Key Project of Natural Science Foundation of the Department of Education of Anhui Province(2025AHGXZK31285)
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Year 2026 volume 24 Issue 8
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60
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Article Info
doi: 10.1016/S1875-5364(26)61196-X
  • Receive Date：2025-11-10
  • Online Date：2026-08-20
  • Published：2026-08-20
Article Data
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History
  • Received：2025-11-10
  • Revised：2025-12-22
  • Accepted：2026-01-19
Funding
National Natural Science Foundation of China(82270879; 82504844)
Foundation of Excellent Youth Scholars of Education Committee of Anhui Province of China(2022AH030124)
Key Project of Natural Science Foundation of the Department of Education of Anhui Province(2025AHGXZK31285)
Affiliations
    1Department of Pharmacology, Wannan Medical College, Wuhu 241002, China
    2Anhui Innovative Center for Drug Basic Research of Metabolic Diseases, Wannan Medical College, Wuhu 241002, China
    3Wuhu Modern Technology Research and Development Center of Chinese Herbal Medicine and Functional Food, Anhui College of Traditional Chinese Medicine, Wuhu 241002, China
    4Department of Endocrinology and Genetic Metabolism, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu 241002, China

Corresponding:

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E-mail address: (G. Wang)
(J. Han)
(H. Che)
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表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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