Umbelliprenin induces autophagy and apoptosis while inhibits cancer cell stemness in pancreatic cancer cells - Research article

Q: What is the main antitumor effect of umbelliprenin in pancreatic cancer cells?

Umbelliprenin inhibits pancreatic cancer cell proliferation in vitro and suppresses tumor growth in vivo.

Q: How does umbelliprenin affect apoptosis and autophagy?

Umbelliprenin induces both apoptosis and autophagy, supported by increased apoptosis/autophagy-related protein expression and functional assays.

Q: What mechanism links umbelliprenin to reduced cancer stemness?

Umbelliprenin reduces pancreatic cancer stemness by lowering Oct4, Nanog, and Sox2 mRNA levels, accompanied by inhibition of Akt/mTOR and Notch1 signaling pathways.

Sep 24, 2026

Uploaded by Sarah

Umbelliprenin is a sesquiterpenecoumarin from Artemisia absinthium with reported antitumor activity via apoptosis, yet its role in human pancreatic cancer remained unclear. The study evaluated antitumor effects using MTT and Annexin V/PI assays in vitro and xenograft models in vivo, alongside immunofluorescence for autophagy and immunoblotting for apoptosis/autophagy proteins. Umbelliprenin suppressed proliferation and tumor growth, induced apoptosis and autophagy, reduced stemness markers, and inhibited Akt/mTOR and Notch1 signaling.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Introduction

Background and rationale

Pancreatic cancer stemness

Autophagy and signaling pathways

Materials and Methods

Chemicals and antibodies

Key assays and in vivo model (overview)

DOI: 10. 1002/cam4 .6170 RESEAR CH ARTICLE Umbelliprenin induces autophagy and apoptosis while inhibits cancer cell stemness in pancreatic cancer cells Hongcheng Wang1,2 | Yongzhi Liu3 | Yiwei Wang1 | Ting Xu1 | Guanggai Xia1 | Xinyu Huang1 1Department of Hepatobiliary and Pancreatic Surgery, Sixth People's Hospital Affiliated Shanghai Jiao Tong University, Shanghai, China 2Department of General Surgery, The Second People’ Hospital of Kashgar, 1S, Kashgar, Xinjiang, China 3Affiliated Xiaoshan Hospital Hangzhou Normal University, Zhejiang, China Correspondence Xinyu Huang, Department of Hepatobiliary and Pancreatic Surgery, Sixth People's Hospital Affiliated Shanghai Jiao Tong University, 600 YiShan Road, Shanghai 200233, China. [Email:](Email: huangxinyu2012@163.com)[ huangxinyu2012@163.com](Email: huangxinyu2012@163.com) Funding information Science and Technology Commission of Shanghai Municipality, Grant/ Award Number: 18ZR1429100 and 18ZR1434200 1 | INTRODUCTION Abstract Background: Umbelliprenin is a sesquiterpenecoumarin isolated from Artemisia absinthium L. and shows antitumor effects in various cancers by inducing apoptosis. However, the antitumor effect of umbelliprenin in human pancreatic cancer has not been clarified. Methods: The antitumor effects were determined by MTT and AnnexinV/PI double staining assay in vitro and xenograft mice in vivo. Autophagy was determined via immunofluorescence analysis. Apoptotic or autophagic related proteins were measured by immunoblotting. The pancreatic cancer cell stemness were determined by mammosphere formation and ALDEFLUOR assay. Results: It revealed that umbelliprenin inhibited pancreatic cancer cell proliferationin vitro and pancreatic cancer tumor growth in vivo. Moreover, umbelliprenin induced pancreatic cancer cell BxPC3 apoptosis and autophagy as evidenced by upregulated apoptosis and autophagy- related protein expression (p <0.01) . Blocking autophagy by 3-MA or Atg7 knockout enhanced umbelliprenin-induced apoptosis (p <0.05) . Umbelliprenin also reduced pancreatic cancer cell stemness by reducing Oct4, Nanog, and Sox2 mRNA levels (p <0.01) . Mechanistically, umbelliprenin greatly inhibited Akt/mTOR and Notch1 signal pathway. Conclusion: Umbelliprenin may be a novel therapeutic approach for pancreatic cancer treatment. KEYWORDS Akt/mTOR signaling pathway, apoptosis, autophagy, cancer stem cells, pancreatic cancer survival rate below 5% .1 The mainstay of chemotherapy combinations such as FOLFIRNOX and gemcitabine/ Pancreatic cancer is one of the most highly lethal malignancy cancers in the world with a 5-year overall nab-paclitaxel only slightly improve pancreatic cancer patients' survival rates but have obvious side effects.2,3 Hongcheng Wang and Yongzhi Liu contributed equally to this work. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. However, other treatment modalities are extremely lacking. Therefore, the development of novel anti-pancreatic cancer agents with fewer side effects are urgently needed. Pancreatic cancer contains various types of cells including a distinct subpopulation of pancreatic cancer stem cells (CSCs) . Pancreatic CSCs contribute to tumor cell selfrenewal, differentiation, cancer recurrence, metastasis, and therapy resistance.4,5 Markers that used to identify pancreatic CSCs include SOX2, OCT4, NANOG, ALDH1, CD24, CD44, and ESA.6,7 Pancreatic CSCs are regulated by aberrant activation of signal pathways like NOTCH, WNT, and β-catenin.8,9 Therefore, targeting these signal pathways may provide new therapeutic strategies in the treatment of pancreatic cancer. In recent years, medicinal plants have grabbed great attention for treating diseases such as cancer.10,11 Artemisia ab

FAQs

What is the main antitumor effect of umbelliprenin in pancreatic cancer cells?

Umbelliprenin inhibits pancreatic cancer cell proliferation in vitro and suppresses tumor growth in vivo.

How does umbelliprenin affect apoptosis and autophagy?

Umbelliprenin induces both apoptosis and autophagy, supported by increased apoptosis/autophagy-related protein expression and functional assays.

What mechanism links umbelliprenin to reduced cancer stemness?

Umbelliprenin reduces pancreatic cancer stemness by lowering Oct4, Nanog, and Sox2 mRNA levels, accompanied by inhibition of Akt/mTOR and Notch1 signaling pathways.

Sep 24, 2026

Uploaded by Sarah