Illustration symbolizing atovaquone's potential in liver cancer treatment.

Can This Unexpected Drug Combat Liver Cancer?

Mira Elwood in Health & Wellness November 2025 • 3 min read.

"Research reveals that atovaquone, an antiparasitic drug, may offer a new approach to overcoming chemoresistance in hepatocellular carcinoma (HCC)."

Hepatocellular carcinoma (HCC), a prevalent malignancy, poses significant treatment challenges due to its high mortality rate and frequent resistance to chemotherapy. Current treatments, including surgery and targeted therapies, often fall short, necessitating the exploration of novel therapeutic strategies.

A recent study published in Biochemical and Biophysical Research Communications sheds light on a potential breakthrough. Researchers investigated the efficacy of atovaquone, an antiparasitic drug, in combating chemoresistance in HCC. The findings suggest that atovaquone could offer a new avenue for treating this challenging cancer.

The study uncovers atovaquone's ability to target mitochondrial respiration, a key energy production process in cells. By disrupting this process, atovaquone demonstrates promising results in overcoming chemoresistance and inhibiting the growth of HCC cells. This article delves into the details of this groundbreaking research and its potential implications for liver cancer treatment.

How Atovaquone Overcomes Chemoresistance in HCC?

Illustration symbolizing atovaquone's potential in liver cancer treatment.

The study's findings reveal that atovaquone exhibits activity against chemoresistant HCC cells at clinically relevant concentrations. The researchers demonstrated that atovaquone inhibits cell proliferation and induces apoptosis (programmed cell death) in both parental HCC cells and cells exposed to prolonged chemotherapy. This dual action suggests a broad therapeutic potential.

Further experiments showed that combining atovaquone with cisplatin or doxorubicin, common chemotherapy drugs, resulted in significantly greater efficacy compared to using either drug alone. This synergistic effect underscores atovaquone's ability to enhance the effectiveness of existing treatments.

Inhibition of Mitochondrial Respiration: Atovaquone targets and suppresses mitochondrial respiration, disrupting the energy supply of HCC cells.
Induction of Oxidative Stress: The drug promotes oxidative stress within cancer cells, leading to damage and cell death.
Selective Action: Atovaquone's effectiveness is linked to mitochondrial function, as it shows limited impact on mitochondrial respiration-deficient cells.
Increased Sensitivity: Chemoresistant HCC cells exhibit higher levels of mitochondrial respiration, making them particularly vulnerable to atovaquone's effects.

In vivo experiments further validated these findings. Mice with chemoresistant HCC tumors treated with atovaquone showed significant inhibition of tumor growth and increased oxidative stress within the tumors. These results reinforce the potential of atovaquone as a therapeutic agent for HCC.

A Promising New Direction

This research highlights the dependency of chemoresistant HCC on mitochondrial respiration and positions atovaquone as a potential drug to overcome chemoresistance. While further studies are needed, these findings offer a promising new direction for developing more effective treatments for hepatocellular carcinoma and improving outcomes for patients facing this challenging disease. The ability to repurpose an existing drug like atovaquone also offers the potential for faster translation to clinical use.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/j.bbrc.2018.11.182, Alternate LINK

Title: Inhibition Of Mitochondrial Respiration Overcomes Hepatocellular Carcinoma Chemoresistance

Subject: Cell Biology

Journal: Biochemical and Biophysical Research Communications

Publisher: Elsevier BV

Authors: Yuan Sun, Hai Xu, Xinju Chen, Xiaodong Li, Baoping Luo

Published: 2019-01-01

Everything You Need To Know

How does Atovaquone specifically work to combat chemoresistance in Hepatocellular Carcinoma (HCC) cells?

Atovaquone is effective because it targets mitochondrial respiration, a crucial energy production process, within Hepatocellular Carcinoma (HCC) cells. By disrupting this process, Atovaquone inhibits the growth of HCC cells and overcomes chemoresistance. Chemoresistant HCC cells exhibit higher levels of mitochondrial respiration, making them particularly vulnerable to Atovaquone's effects. Furthermore, Atovaquone induces oxidative stress within the cancer cells, leading to damage and cell death. Atovaquone has a selective action and shows limited impact on mitochondrial respiration-deficient cells.

Can Atovaquone be used in combination with existing chemotherapy treatments for Hepatocellular Carcinoma (HCC), and if so, what are the benefits?

Research indicates that combining Atovaquone with common chemotherapy drugs like Cisplatin or Doxorubicin can lead to a synergistic effect, resulting in significantly greater efficacy compared to using either drug alone. This means Atovaquone enhances the effectiveness of existing treatments by sensitizing the Hepatocellular Carcinoma (HCC) cells to chemotherapy. This combined approach can potentially improve patient outcomes by more effectively targeting and eliminating chemoresistant cancer cells.

What types of experiments were conducted to determine the effectiveness of Atovaquone against chemoresistant Hepatocellular Carcinoma (HCC)?

The research involved both in vitro and in vivo experiments. In vitro studies demonstrated that Atovaquone inhibits cell proliferation and induces apoptosis (programmed cell death) in both parental Hepatocellular Carcinoma (HCC) cells and cells exposed to prolonged chemotherapy. In vivo experiments on mice with chemoresistant HCC tumors treated with Atovaquone showed significant inhibition of tumor growth and increased oxidative stress within the tumors. These findings collectively suggest that Atovaquone holds promise as a therapeutic agent for HCC.

What are the different mechanisms of action exhibited by Atovaquone that make it a potential treatment for Hepatocellular Carcinoma (HCC)?

Atovaquone's action involves the inhibition of mitochondrial respiration, the induction of oxidative stress, selective action against cells dependent on mitochondrial function, and increased sensitivity in chemoresistant Hepatocellular Carcinoma (HCC) cells. Specifically, it targets and suppresses mitochondrial respiration, disrupting the energy supply of HCC cells. Additionally, it promotes oxidative stress within cancer cells, leading to damage and cell death. Further studies are needed to understand if Atovaquone impacts the entire mitochondria or specific complexes.

What are the limitations and future research directions for using Atovaquone as a treatment for Hepatocellular Carcinoma (HCC)?

While Atovaquone shows promise in treating Hepatocellular Carcinoma (HCC), it's important to consider potential side effects, optimal dosages, and long-term effectiveness in humans. Further clinical trials are needed to assess its safety and efficacy in a larger patient population. Additionally, understanding the mechanisms of resistance to Atovaquone itself and developing strategies to overcome such resistance will be crucial. There is further study needed to understand how Atovaquone combines with current targeted therapies.