ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Induction of Apoptosis by Ethanol Extract of Sapodilla Leaf in HGT-1 Cells Involved Caspase-Independent Signal Transduction Pathway and Activation of Nrf2/HO-1
Bee Ling Tan 1
Lee Chin Chan 2
1. Faculty of Health and Life Sciences, Management and Science University, Shah Alam, Malaysia
2. Biovalence Sdn. Bhd., 22, Jalan SS25/34, Taman Mayang, 47301 Petaling Jaya, Selangor, Malaysia, Petaling Jaya, Malaysia
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Abstract
Gastric cancer has become one of the most common cancers globally. Sapodilla or known as Manilkara zapota (L.) P. Royen, has been traditionally applied for cough, cold, and diarrhea. The detailed mechanisms in modulating sapodilla leaf 70% ethanol extract against HGT-1 human gastric cancer cell line have yet to be fully studied. Apoptosis induction was evaluated using an Annexin V-FITC/PI staining kit with flow cytometry. Caspase-3 and -8 expression were determined by colorimetric analysis. To explore the molecular mechanisms of action of the 70% ethanol extract of sapodilla leaves in HGT-1 cells, quantitative real-time PCR (qPCR) was performed. Overall analyses demonstrated that sapodilla leaf 70% ethanol extract was cytotoxic and suppressed the growth of HGT-1 cells. The 70% ethanol extract of sapodilla leaves significantly suppressed the proliferation of HGT-1 cells. Moreover, it enhanced the expression of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), while concurrently suppressing the transcriptional activities of nuclear factor-kappa B (NF-κB) and inducible nitric oxide synthase (iNOS). Results indicate that sapodilla leaf 70% ethanol extract has an anti-gastric cancer effect via modulation of multiple signaling pathways. Sapodilla leaf 70% ethanol extract demonstrates promising potential as an anti-gastric cancer agent.
Summary
Keywords
Apoptosis, Bcl-2, caspase-8, Cytotoxicity, gastric cancer
Received
04 February 2026
Accepted
19 February 2026
Copyright
© 2026 Tan and Chan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Bee Ling Tan
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.