Extended sub-chronic exposure to heavy metal mixture induced multidrug resistance against chemotherapy agents in ovarian cancer cells Original paper
Researched by:
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Divine Aleru
ID
Divine Aleru
Read MoreI am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
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Women’s Health
Women’s Health
Women’s health, a vital aspect of medical science, encompasses various conditions unique to women’s physiological makeup. Historically, women were often excluded from clinical research, leading to a gap in understanding the intricacies of women’s health needs. However, recent advancements have highlighted the significant role that the microbiome plays in these conditions, offering new insights and potential therapies. MicrobiomeSignatures.com is at the forefront of exploring the microbiome signature of each of these conditions to unravel the etiology of these diseases and develop targeted microbiome therapies.
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Metals
Metals
OverviewHeavy metals play a significant and multifaceted role in the pathogenicity of microbial species. Their involvement can be viewed from two primary perspectives: the toxicity of heavy metals to microbes and the exploitation of heavy metals by microbial pathogens to establish infections and evade the host immune response. Understanding these aspects is critical for both […]
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Ovarian Cancer
Ovarian Cancer
OverviewOvarian cancer (OC) remains one of the most deadly cancers affecting women, with an estimated 320,000 new cases diagnosed worldwide annually, making it the eighth most commonly diagnosed cancer. It also accounts for over 200,000 deaths each year, reflecting its high lethality. The disease is often diagnosed at advanced stages (stage III and IV) due […]
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Divine Aleru
Read More
Researched by:
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Divine Aleru
ID
Divine Aleru
Read More
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Divine Aleru
What was studied?
The research investigates how chronic exposure to a mixture of lead (Pb), cadmium (Cd), and cobalt (Co) at low, non-lethal doses can induce multidrug resistance (MDR) in the NIH-Ovcar3 human ovarian cancer cell line. The study focuses on whether prolonged exposure to these heavy metals results in resistance to chemotherapy drugs like cisplatin (CP), 5-fluorouracil (5-FU), and doxorubicin (DX), and explores the molecular mechanisms behind this resistance. The research aims to uncover whether the heavy metals could influence drug efflux pumps and apoptosis pathways, making chemotherapy less effective.
Who was studied?
The study utilized the NIH-Ovcar3 human ovarian cancer cell line, which is commonly used for research into chemotherapy resistance. The cells were exposed to a mixture of Pb, Cd, and Co at concentrations that were below known harmful levels, simulating the chronic exposure seen in real-world environments. The research observed the development of multidrug resistance over several generations (20 passages) to investigate how these cells adapted to low-dose heavy metal exposure. This was followed by treatment with chemotherapy agents to examine how the exposure affected the cells’ responses to these drugs.
Most important findings
The study showed that prolonged exposure to low doses of Pb, Cd, and Co resulted in significant chemotherapy resistance in the ovarian cancer cells. These resistant cells exhibited cross-resistance to three chemotherapy agents: cisplatin, 5-fluorouracil, and doxorubicin. The most pronounced resistance was observed against cisplatin and doxorubicin, where resistant cells had over 2.1 and 2.87 times higher IC50 values compared to controls. Furthermore, the study highlighted the role of ATP-binding cassette (ABC) transporters, particularly P-glycoprotein (ABCB1), Breast Cancer Resistance Protein (ABCG2), and Multidrug Resistance-associated Protein 1 (ABCC1), in this resistance mechanism. These transporters were significantly overexpressed in the resistant cell population, supporting the hypothesis that heavy metal exposure upregulates cellular detoxification pathways. Additionally, the resistant cells exhibited lower apoptotic activity and increased motility, suggesting that the exposure may also contribute to a more invasive and metastatic phenotype.
Key implications
The findings of this study suggest that even low levels of heavy metal exposure, which are often deemed safe, could contribute to the development of multidrug resistance in ovarian cancer cells. This has critical implications for clinical practice, especially in environments with high environmental contamination. The study emphasizes the need for monitoring heavy metal exposure in patients with ovarian cancer, particularly in those undergoing chemotherapy, as it could influence the efficacy of treatment. Understanding the molecular mechanisms, including the involvement of ABC transporters and reduced apoptosis, offers potential targets for overcoming resistance and improving therapeutic strategies. This research also calls for further exploration of how environmental exposures to heavy metals might affect cancer progression and drug resistance over time.