2. Academic Validation
  3. 4'-Demethylpodophyllotoxin functions as a mechanism-driven therapy by targeting the PI3K-AKT pathway in Colorectal cancer

4'-Demethylpodophyllotoxin functions as a mechanism-driven therapy by targeting the PI3K-AKT pathway in Colorectal cancer

  • Transl Oncol. 2025 Jan:51:102199. doi: 10.1016/j.tranon.2024.102199.
Jun Liu 1,  Dandong Luo 2,  Xiaochuan Chen 3,  Jiaqi Liu 1,  Junxiong Chen 1,  Mengchen Shi 1,  Haiyan Dong 1,  Yucheng Xu 2,  Xinyou Wang 4,  Zhaoliang Yu 5,  Huanliang Liu 6,  Yanchun Feng 7
Affiliations

Affiliations

  • 1 Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, PR China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, PR China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, PR China.
  • 2 Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, PR China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, PR China; Department of General Surgery (Pancreatic Hepatobiliary Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, PR China.
  • 3 Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, PR China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, PR China; Department of Obstetrics and Gynecology, The Sixth Affiliated Hospital, Sun Yat-sen University, PR China.
  • 4 Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, PR China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, PR China; Department of General Surgery (Stomach Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, PR China.
  • 5 Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, PR China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, PR China; Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, PR China.
  • 6 Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, PR China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, PR China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, PR China. Electronic address: liuhuanl@mail.sysu.edu.cn.
  • 7 Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, PR China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, PR China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, PR China. Electronic address: fengych26@mail.sysu.edu.cn.
PMID: 39631206 DOI: 10.1016/j.tranon.2024.102199
Abstract

The treatment of colorectal Cancer (CRC) poses significant challenges in terms of drug resistance and poor prognosis, necessitating the exploration of effective therapeutic strategies. In this study, high-throughput drug screening was utilized to identify Chinese herbal medicines with notable therapeutic effects on CRC. Among the compounds identified, 4'-demethylpodophyllotoxin (DOP), a derivative of podophyllotoxin, emerged as a potent anti-cancer compound. DOP exhibited time- and dose-dependent growth inhibition on CRC cell lines and tumor organoids derived from patients. RNA-seq revealed that DOP activated the PI3K-AKT pathway, leading to tumor cell Apoptosis and cell cycle arrest at the G2/M phase. Additionally, DOP induced DNA damage in CRC cells. To further validate its therapeutic efficacy in CRC, the DLD1-derived xenograft model demonstrated that DOP effectively suppressed CRC growth in vivo. In conclusion, these findings highlight the significant therapeutic potential of DOP as an anti-tumor drug for treating CRC, thereby opening new avenues for investigating Podophyllotoxin derivatives in this specific field.

Keywords

4′-Demethylpodophyllotoxin; Chemoresistance; Colorectal cancer; PI3K-AKT pathway.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z