Int J Biol Sci 2021; 17(11):2811-2825. doi:10.7150/ijbs.60674 This issue

Research Paper

Ailanthus Altissima-derived Ailanthone enhances Gastric Cancer Cell Apoptosis by Inducing the Repression of Base Excision Repair by Downregulating p23 Expression

Chun-ming Wang1,2,3#, Hua-fu Li1,4,5#, Xiao-kun Wang1,2#, Wu-guo Li6#, Qiao Su6, Xing Xiao7, Teng-fei Hao1,2, Wei Chen7, Ya-wei Zhang1,2, Hai-yong Zhang1,2, Wang Wu1,2, Zhen-ran Hu7, Guang-yin Zhao6, Ming-yu Huo1✉, Yu-long He1,2✉, Chang-hua Zhang1✉

1. Digestive Disease Center, The Seventh Affiliated Hospital of Sun Yat‑Sen University, Shenzhen, Guangdong 518107, P.R. China.
2. Department of Gastrointestinopancreatic Surgery, The First Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China.
3. Department of Intervention, The People's Hospital of Guangxi Zhuang Autonomous Region,Nanning Guangxi 530021,P.R. China.
4. Adult Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
5. The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
6. Animal Experiment Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, P.R. China.
7. Scientific research center, The Seventh Affiliated Hospital of Sun Yat‑Sen University, Shenzhen, Guangdong 518107, P.R.China.
#These authors contributed equally to this work.

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Citation:
Wang Cm, Li Hf, Wang Xk, Li Wg, Su Q, Xiao X, Hao Tf, Chen W, Zhang Yw, Zhang Hy, Wu W, Hu Zr, Zhao Gy, Huo My, He Yl, Zhang Ch. Ailanthus Altissima-derived Ailanthone enhances Gastric Cancer Cell Apoptosis by Inducing the Repression of Base Excision Repair by Downregulating p23 Expression. Int J Biol Sci 2021; 17(11):2811-2825. doi:10.7150/ijbs.60674. Available from https://www.ijbs.com/v17p2811.htm

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Abstract

Graphic abstract

Chemotherapy plays an irreplaceable role in the treatment of GC, but currently available chemotherapeutic drugs are not ideal. The application of medicinal plants is an important direction for new drug discovery. Through drug screening of GC organoids, we determined that ailanthone has an anticancer effect on GC cells in vitro and in vivo. We also found that AIL can induce DNA damage and apoptosis in GC cells. Further transcriptome sequencing of PDX tissue indicated that AIL inhibited the expression of XRCC1, which plays an important role in DNA damage repair, and the results were also confirmed by western blotting. In addition, we found that AIL inhibited the expression of P23 and that inhibition of P23 decreased the expression of XRCC1, indicating that AIL can regulate XRCC1 via P23. The results of coimmunoprecipitation showed that AIL can inhibit the binding of P23 and XRCC1 to HSP90. These findings indicate that AIL can induce DNA damage and apoptosis in GC cells. Meanwhile, AIL can decrease XRCC1 activity by downregulating P23 expression to inhibit DNA damage repair. The present study sheds light on the potential application of new drugs isolated from natural medicinal plants for GC therapy.

Keywords: Ailanthone, Gastric cancer, P23, Organoids, BER