Canady Helios Cold Plasma Induces Breast Cancer Cell Death by Oxidation of Histone mRNA
Xiaoqian Cheng1, Saravana R K Murthy1, Taisen Zhuang1
1Jerome Canady Research Institute for Advanced Biological and Technological Sciences, Takoma Park, MD 20912, USA.
Abstract:
Breast cancer is the most common cancer among women worldwide. Its molecular receptor marker status and mutational subtypes complicate clinical therapies. Cold atmospheric plasma is a promising adjuvant therapy to selectively combat many cancers, including breast cancer, but not normal tissue; however, the underlying mechanisms remain unexplored. Here, four breast cancer cell lines with different marker status were treated with Canady Helios Cold Plasma™ (CHCP) at various dosages and their differential progress of apoptosis was monitored. Inhibition of cell proliferation, induction of apoptosis, and disruption of the cell cycle were observed. At least 16 histone mRNA types were oxidized and degraded immediately after CHCP treatment by 8-oxoguanine (8-oxoG) modification. The expression of DNA damage response genes was up-regulated 12 h post-treatment, indicating that 8-oxoG modification and degradation of histone mRNA during the early S phase of the cell cycle, rather than DNA damage, is the primary cause of cancer cell death induced by CHCP. Our report demonstrates for the first time that CHCP effectively induces cell death in breast cancer regardless of subtyping, through histone mRNA oxidation and degradation during the early S phase of the cell cycle.
Insights
Cold atmospheric plasma (CAP) effectively combats breast cancer by inducing cell death. This therapy targets histone mRNA degradation during the early S phase, offering a novel treatment approach regardless of cancer subtype.
Area of Science:
- Oncology
- Biophysics
- Molecular Biology
Background:
- Breast cancer is a leading global cancer in women, with complex subtypes complicating treatment.
- Cold atmospheric plasma (CAP) shows potential as an adjuvant therapy for various cancers, including breast cancer, sparing normal tissues.
- The precise mechanisms by which CAP exerts its anti-cancer effects remain largely unelucidated.
Purpose of the Study:
- To investigate the efficacy of Canady Helios Cold Plasma™ (CHCP) against diverse breast cancer cell lines.
- To elucidate the molecular mechanisms underlying CHCP-induced breast cancer cell death.
- To determine if CHCP's effectiveness is dependent on specific breast cancer subtypes.
Main Methods:
- Treatment of four distinct breast cancer cell lines with varying marker statuses using CHCP at different dosages.
- Monitoring of apoptosis, cell proliferation, and cell cycle progression post-CHCP exposure.
- Analysis of histone mRNA modifications (8-oxoguanine) and DNA damage response gene expression.
Main Results:
- CHCP treatment inhibited proliferation, induced apoptosis, and disrupted the cell cycle in breast cancer cells.
- Immediate oxidation and degradation of at least 16 histone mRNA types via 8-oxoguanine modification were observed.
- Upregulation of DNA damage response genes occurred 12 hours post-treatment, suggesting a secondary effect.
Conclusions:
- CHCP induces breast cancer cell death irrespective of molecular subtype.
- The primary mechanism involves 8-oxoguanine modification and degradation of histone mRNA during the early S phase of the cell cycle.
- This study reveals a novel pathway for CAP-mediated cancer therapy, distinct from direct DNA damage.
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