Gastric cancer cells under attack by bufalin, experiencing endoplasmic reticulum stress.

Unlock Bufalin's Potential: How This Compound Fights Gastric Cancer

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Theo Raines in Health & Wellness October 2026 • 4 min read.

"Discover how bufalin, a compound derived from traditional medicine, targets human gastric cancer cells by disrupting endoplasmic reticulum stress and enhancing apoptosis."


Gastric cancer remains a significant global health challenge, especially in regions like China, Japan, and South Korea. While early detection and surgery offer high survival rates, advanced stages of the disease often present a grim prognosis, complicated by drug resistance. Traditional chemotherapies, though helpful, frequently encounter resistance, underscoring the pressing need for innovative treatments.

Bufalin, a key component extracted from Chan Su, a traditional Chinese medicine, has emerged as a promising candidate. Studies indicate its potential to inhibit the proliferation and induce apoptosis in various cancer cell lines without significant side effects. However, the precise mechanisms behind its anti-tumor effects have remained elusive.

Recent research has shed light on how bufalin combats gastric cancer cells by inducing endoplasmic reticulum (ER) stress and modulating autophagy, a cellular self-cleaning process. This article delves into these mechanisms, explaining how bufalin enhances apoptosis (programmed cell death) in gastric cancer cells by blocking autophagy, offering new avenues for treatment strategies.

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Bufalin and Gastric Cancer Treatment Research

The supplied sources describe chemotherapy and radiotherapy as treatments for advanced gastric cancer, noting that about two-thirds of patients are diagnosed at an advanced stage because early disease can have few symptoms. They also report that research on bufalin in gastric cancer remains limited and its targets have not been clearly established. A 2026 study reports that bufalin reversed oxaliplatin resistance in gastric cancer and presents Huachansu injection as a potential clinical application, but this is a research finding rather than evidence of established clinical use.

A Decade of Bufalin Research

A review traces research into bufalin and drug resistance in cancer across 2013–2022, describing bufalin as a bufadienolide found in toad venom and a subject of in vitro and in vivo study. A 2024 bibliometric analysis reports inhibitory effects of bufalin across several tumour types, including gastric cancer, and examines published research trends. These sources situate bufalin research within a broader cancer-research history, but do not identify a specific foundational discovery of bufalin's effect on gastric cancer.

Bufalin's Multifaceted Attack on Gastric Cancer Cells

Gastric cancer cells under attack by bufalin, experiencing endoplasmic reticulum stress.

The study reveals that bufalin significantly suppresses the growth of human gastric cancer (HGC) cells, specifically SGC7901 and BGC823 cell lines, in a dose- and time-dependent manner. This means the higher the concentration of bufalin and the longer the exposure, the more effective it is at inhibiting cancer cell proliferation. Importantly, bufalin shows minimal impact on normal gastric cells, indicating a selective toxicity towards cancer cells.

Apoptosis, or programmed cell death, is a crucial mechanism in cancer treatment. Bufalin actively promotes apoptosis in HGC cells. The research pinpoints that bufalin achieves this by:

  • Increasing the Bax/Bcl-2 ratio: This is vital for mitochondrial-mediated apoptosis.
  • Activating caspase-3: A key executioner protein in the apoptotic pathway.
  • Inducing ER Stress: Disrupting the endoplasmic reticulum, leading to cellular dysfunction and eventual death.
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Research on Bufalin's Effects

A 2026 study reports that bufalin targets YBX1, which is upregulated in oxaliplatin-resistant gastric cancer cells; YBX1 activates STC1 expression, and the study investigates how bufalin reverses resistance. A 2022 review reports that bufalin had a marginal effect on a normal gastric mucous epithelial cell line at concentrations up to 200 nmol/L. Separately, a study of benzyl isothiocyanate—not bufalin—notes that about two-thirds of gastric cancer patients are diagnosed at an advanced stage, when treatment may involve chemotherapy or radiotherapy.

A Mechanistic Qualification

In human gastric cancer cells, the reported effect of bufalin depended on the endoplasmic-reticulum stress pathway component IRE1: knocking down IRE1 greatly abolished bufalin's apoptosis-inducing effect in HGC cells. By contrast, knocking down CHOP did not abolish that effect. This finding qualifies a simple account of bufalin-induced cell death by showing that the observed response was not equally dependent on both tested pathway components.

Autophagy, a cellular process where cells degrade and recycle their components, can sometimes protect cancer cells. However, bufalin appears to tip the balance towards cell death by modulating this process. The study found that while bufalin initially induces autophagy, blocking this autophagy significantly enhances bufalin-induced apoptosis. This suggests that autophagy, in this context, acts as a survival mechanism for cancer cells, and inhibiting it makes them more vulnerable to bufalin's cytotoxic effects.

Implications for Future Therapies

This research highlights bufalin as a promising compound for gastric cancer treatment, particularly due to its ability to induce ER stress and modulate autophagy. By understanding these mechanisms, scientists can develop more effective strategies to target and eliminate cancer cells.

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Research Priorities and Clinical Context

A review of gastric cancer treatment summarizes pivotal clinical trials and discusses management of localized and metastatic disease, including developments in immunotherapy, targeted therapy, individualized treatment, and future perspectives. A separate review examines bufalin research on overcoming cancer drug resistance from 2013–2022, based on in vitro and in vivo work. A 2024 bibliometric analysis maps the authors, institutions, and countries contributing to bufalin cancer research and identifies collaboration and knowledge sharing as ways to support future research.

Evidence from Cell Studies

A study tested bufalin in MGC803 and SGC7901 gastric cancer cells at doses of 0, 25, 50, 75, 100, 150, and 200 nmol/L for 48 hours, measuring cell viability with a CCK-8 kit. The study describes investigating bufalin's effects on cell proliferation and apoptosis. The supplied material reports these laboratory conditions but does not provide clinical outcomes or evidence about treatment in patients.

The discovery that blocking autophagy enhances bufalin-induced apoptosis opens new therapeutic avenues. Future treatments might combine bufalin with autophagy inhibitors to maximize its cytotoxic effects on gastric cancer cells.

While these findings are encouraging, further research is essential. Clinical trials are needed to assess the safety and efficacy of bufalin-based therapies in humans. Understanding the optimal dosage, delivery methods, and potential side effects will be crucial for translating these laboratory findings into effective cancer treatments.

What cell-line experiments can establish

In vitro (cell or tissue) study (level 6 of 8)

This was an in vitro study in human gastric cancer cell lines, so it can show how bufalin affected these cells under laboratory conditions, not whether it treats cancer in people.[1]

The measured outcomes included proliferation and apoptosis, alongside ER stress and autophagy; they do not establish patient outcomes or clinical benefit.[1]

How the cell findings fit together

The findings link bufalin exposure with signs of cell death and ER stress, while the IRE1 knockdown result suggests that this response relies more on IRE1 than on every measured ER-stress component equally.[2]

Autophagy appears to be a cellular response that can temper the effect: disrupting it with either a chemical inhibitor or gene silencing intensified apoptosis in these experiments.[1]

Together, the results describe interacting stress, recycling, and cell-death processes in cultured cancer cells; they do not show that the same interactions determine outcomes in a whole organism.[1]

What keeps the mechanism from being settled

  • JNK inhibition reduced apoptosis in control cells but not after IRE1 knockdown, complicating a simple account of the pathway.[2]
  • The paper notes that mechanisms behind bufalin's anti-tumor activity remain incompletely understood.[1]

Bufalin, ER stress, and autophagy in gastric cancer cell lines

Study designIn vitro (cell or tissue) study[1]
Duration48 h, or 1, 2, 3 and 4 days[1]
ComparisonVehicle[1]
Main outcomeProliferation and apoptosis, including the roles of ER stress and autophagy[1]
Times cited32[1]

Questions left by these experiments

  • Would the same dependence on IRE1 and the same effect of blocking autophagy appear in gastric cancer models beyond the two cell lines studied?[1] [2]

Terms used in the study

Autophagy
A cellular process examined for its role in bufalin-induced apoptosis[1]

Sources

  1. Blocking autophagy enhances the pro-apoptotic effect of bufalin on human gastric cancer cells through endoplasmic reticulum stress (The Company of Biologists, 2017)
  2. Blocking autophagy enhances the pro-apoptotic effect of bufalin on human gastric cancer cells through endoplasmic reticulum stress (Europe PMC, 2017)

About this Article -

Written with AI assistance from published research, and reviewed by the Mystum team. See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1242/bio.026344, Alternate LINK

Title: Blocking Autophagy Enhances The Pro-Apoptotic Effect Of Bufalin On Human Gastric Cancer Cells Through Endoplasmic Reticulum Stress

Subject: General Agricultural and Biological Sciences

Journal: Biology Open

Publisher: The Company of Biologists

Authors: Hongyan Zhao, Qinghua Li, Jie Pang, Huilin Jin, Hongwei Li, Xiaoying Yang

Published: 2017-01-01

Everything You Need To Know

1

What is Bufalin and why is it important in the context of gastric cancer treatment?

Bufalin is a compound extracted from Chan Su, a traditional Chinese medicine. It is being investigated for its potential in treating gastric cancer. Its significance lies in its ability to target and eliminate human gastric cancer cells, offering a potential alternative to conventional treatments which are often hindered by drug resistance. Bufalin's origin in traditional medicine adds a layer of historical context and potential for further research into natural compounds for cancer therapy.

2

What is apoptosis, and how does bufalin contribute to it in gastric cancer cells?

Apoptosis is programmed cell death, a crucial process where cells self-destruct, and it is a key strategy in cancer treatment. Bufalin enhances apoptosis in human gastric cancer (HGC) cells by increasing the Bax/Bcl-2 ratio, activating caspase-3, and inducing endoplasmic reticulum (ER) stress. By promoting apoptosis, bufalin aims to eliminate cancer cells, offering a targeted approach to combat the disease, potentially improving patient outcomes by reducing the number of cancer cells and preventing tumor growth.

3

What is endoplasmic reticulum (ER) stress, and why is it relevant to the action of bufalin?

Endoplasmic reticulum (ER) stress is a cellular condition where the ER, responsible for protein folding and processing, is disrupted, leading to cellular dysfunction and ultimately cell death. Bufalin induces ER stress in human gastric cancer (HGC) cells, contributing to apoptosis. This is important because cancer cells can sometimes evade cell death, and by inducing ER stress, bufalin overcomes this resistance, triggering the self-destruction of cancer cells. The implications are that by targeting the ER, bufalin can make cancer cells more vulnerable to cell death.

4

How does bufalin interact with autophagy, and what does this interaction mean for cancer treatment?

Autophagy is a cellular process where cells degrade and recycle their components, often acting as a survival mechanism. In the context of bufalin's effects, autophagy appears to protect cancer cells. Bufalin initially induces autophagy but ultimately enhances apoptosis by blocking it. This suggests that cancer cells use autophagy to survive, and by inhibiting it, bufalin makes these cells more susceptible to programmed cell death. This is significant because it shows that bufalin doesn't just promote cell death; it also tackles the cancer cells' defenses, enhancing its effectiveness as a treatment.

5

What are the potential implications of bufalin research for future therapies?

Bufalin's ability to induce ER stress and modulate autophagy suggests it could be a foundation for new gastric cancer treatments. Current research suggests that, by understanding how bufalin interacts with cancer cells, scientists can create more effective treatments. For example, it opens the door to combination therapies where bufalin is used with other drugs or treatments to enhance its effects. Further research can potentially lead to clinical trials and, ultimately, new treatment options.

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