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.
Highlights
Breast carcinomas can be categorized into different entities based on clinical behavior, histologic features, and/or by biological properties, which is important for the discovery of novel treatments, the study of tumor evolution, and the identification of mechanisms of treatment resistance [1]
Tumors with expression of either the estrogen receptor (ER) or progesterone receptor (PR) in at least 1% of tumor cells are categorized as hormone receptorpositive (HR+ ) [2], and intrinsic subtypes of breast cancer are classified into luminal A
In this study we report that degradation of histone RNA in breast cancer cells by Canady Helios Cold PlasmaTM (CHCP) treatment leads to cell death, which is the key differentiating factor for the selective induction of cell death in breast cancer cells
Summary
Breast carcinomas can be categorized into different entities based on clinical behavior, histologic features, and/or by biological properties, which is important for the discovery of novel treatments, the study of tumor evolution, and the identification of mechanisms of treatment resistance [1]. Tumors with expression of either the estrogen receptor (ER) or progesterone receptor (PR) in at least 1% of tumor cells are categorized as hormone receptorpositive (HR+ ) [2], and intrinsic subtypes of breast cancer are classified into luminal A (ER+ /PR+/− /HER2− ), luminal B (ER+ /PR+/− /HER2+/− ), basal-like (ER− /PR− /HER2− ), and HER2-positive (ER− /PR− /HER2+ ) [3,4]. Systemic and local treatments are addressed by three major breast cancer subtypes: HR+ HER2− , HER2+ , and TNBC [5]. About 70% of breast cancer cases are HR+ HER2− [6] and endocrine agents are used to down-regulate ER signaling. Basal-like (TNBC) makes up approximately 15% of breast cancer cases [6] and its molecular pathophysiology remains poorly understood
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
