Canady Helios Cold Plasma Induces Breast Cancer Cell Death by Oxidation of Histone mRNA

Cheng, Xiaoqian; Murthy, Saravana R. K.; Zhuang, Taisen; Ly, Lawan; Jones, Olivia; Basadonna, Giacomo; Keidar, Michael; Kanaan, Yasmine; Canady, Jerome

doi:10.3390/ijms22179578

Cited by 15 publications

(19 citation statements)

References 85 publications

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“…Initially identified in our previous studies on carcinoma cell lines [38,43], inhibition of Ki67 expression and initiation of apoptosis by CHCP was replicated in this study on liposarcoma cells. We also observed a spike in the number of liposarcoma cells in the S/G2/M phase followed by initiation of cell death, consistent with our recent study on breast cancer cell lines [38]. This previous study demonstrated that CHCP permanently disrupts the cell cycle through specific 8-oxoG modification of histone mRNA during the early S-phase.…”

Section: Discussionmentioning

confidence: 52%

“…This previous study demonstrated that CHCP permanently disrupts the cell cycle through specific 8-oxoG modification of histone mRNA during the early S-phase. This compromises the stability of histone mRNA, leading to chromatin destabilization and apoptotic cell death [38]. Although this was demonstrated in breast cancer cells, it is possible that CHCP also induces oxidation of histone mRNA in liposarcoma cells, which will require confirmation.…”

Section: Discussionmentioning

confidence: 99%

“…CHCP is an advantageous adjuvant treatment since it is well-tolerated (26-30 • C) and does not cause thermal or physical damage to normal tissue [36,37]. It is primarily understood that CHCP induces apoptosis in cancer cells through 8-oxoG modification of histone RNA, degradation of histone RNA, and chromatin destabilization during S-phase [38]. As demonstrated in our previous studies, CHCP treatment reduced cell viability by 80-99% across numerous carcinoma cell lines (e.g., renal adenocarcinoma, colorectal carcinoma, pancreatic adenocarcinoma, ovarian adenocarcinoma, esophageal adenocarcinoma, and multiple breast adenocarcinomas) [36,37,39].…”

Section: Introductionmentioning

confidence: 99%

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Canady Cold Helios Plasma Reduces Soft Tissue Sarcoma Viability by Inhibiting Proliferation, Disrupting Cell Cycle, and Inducing Apoptosis: A Preliminary Report

Ly¹,

Cheng²,

Murthy³

et al. 2022

Molecules

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Soft tissue sarcomas (STS) are a rare and highly heterogeneous group of solid tumors, originating from various types of connective tissue. Complete removal of STS by surgery is challenging due to the anatomical location of the tumor, which results in tumor recurrence. Additionally, current polychemotherapeutic regimens are highly toxic with no rational survival benefit. Cold atmospheric plasma (CAP) is a novel technology that has demonstrated immense cancer therapeutic potential. Canady Cold Helios Plasma (CHCP) is a device that sprays CAP along the surgical margins to eradicate residual cancer cells after tumor resection. This preliminary study was conducted in vitro prior to in vivo testing in a humanitarian compassionate use case study and an FDA-approved phase 1 clinical trial (IDE G190165). In this study, the authors evaluate the efficacy of CHCP across multiple STS cell lines. CHCP treatment reduced the viability of four different STS cell lines (i.e., fibrosarcoma, synovial sarcoma, rhabdomyosarcoma, and liposarcoma) in a dose-dependent manner by inhibiting proliferation, disrupting cell cycle, and inducing apoptosis-like cell death.

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Canady Cold Helios Plasma Reduces Soft Tissue Sarcoma Viability by Inhibiting Proliferation, Disrupting Cell Cycle, and Inducing Apoptosis: A Preliminary Report

Ly¹,

Cheng²,

Murthy³

et al. 2022

Molecules

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“…Furthermore, a drastic reduction in G1 phase cells and an increase in S/G2 phase cells compared to control groups after CHCP treatment at 80p 5 min is because of the histone mRNA degradation and a pause in cell division which in turn accumulates more cells at late S phase 37 . This phenomenon is more pronounced in cells treated with siRNA-BCL2A1 in combination with the CHCP treatment suggesting that silencing BCL2A1 expression increases cell death.…”

Section: Discussionmentioning

confidence: 95%

“…Complete inhibition of cell proliferation by downregulation of MYC expression and G1 cell cycle arrest was observed after CPI203 treatment in neuroendocrine tumors 38 . Recently we showed that 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 37 . How the cell cycle arrest induced by CPI203, and histone mRNA degradation induced by CAP treatment would increase the potency of cell death in combination should be determined.…”

Section: Discussionmentioning

confidence: 99%

BCL2A1 regulates Canady Helios Cold Plasma-induced cell death in triple-negative breast cancer

Murthy¹,

Cheng²,

Zhuang³

et al. 2022

Sci Rep

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Breast cancer is the leading cause of cancer death among women. Triple-negative breast cancer (TNBC) has a poor prognosis and frequently relapses early compared with other subtypes. The Cold Atmospheric Plasma (CAP) is a promising therapy for prognostically poor breast cancer such as TNBC. The Canady Helios Cold Plasma (CHCP) induces cell death in the TNBC cell line without thermal damage, however, the mechanism of cell death by CAP treatment is ambiguous and the mechanism of resistance to cell death in some subset of cells has not been addressed. We investigate the expression profile of 48 apoptotic and 35 oxidative gene markers after CHCP treatment in six different types of breast cancer cell lines including luminal A (ER+ PR+/−HER2−), luminal B (ER+PR+/−HER2+), (ER−PR−HER2+), basal-like: ER−PR−HER2− cells were tested with CHCP at different power settings and at 4 different incubation time. The expression levels of the gene markers were determined at 4 different intervals after the treatment. The protein expression of BCL2A1 was only induced after CHCP treatment in TNBC cell lines (p < 0.01), whereas the HER2-positive and ER, PR positive cell lines showed little or no expression of BCL2A1. The BCL2A1 and TNF-alpha expression levels showed a significant correlation within TNBC cell lines (p < 0.01). Silencing BCL2A1 mRNA by siRNA increased the potency of the CHCP treatment. A Combination of CHCP and CPI203, a BET bromodomain inhibitor, and a BCL2A1 antagonist increased the CHCP-induced cell death (p < 0.05). Our results revealed that BCL2A1 is a key gene for resistance during CHCP induced cell death. This resistance in TNBCs could be reversed with a combination of siRNA or BCL2A1 antagonist-CHCP therapy.

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Recent advances in cold atmospheric plasma (CAP) for breast cancer therapy

Chupradit

Widjaja

Majeed

et al. 2022

Cell Biology International

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The serious problems of conventional breast cancer therapy strategies such as drug resistance, severe side effects, and lack of selectivity prompted the development of various cold atmospheric plasma (CAP) devices. Due to its advanced technology, CAP can produce a unique environment rich in reactive oxygen and nitrogen species (RONS), photons, charged ions, and an electric field, making it a promising revolutionary platform for cancer therapy. Despite substantial technological successes, CAP‐based therapeutic systems are encounter with distinct limitations, including low control of the generated RONS, poor knowledge about its anticancer mechanisms, and challenges concerning designing, manufacturing, clinical translation, and commercialization, which must be resolved. The latest developments in CAP‐based therapeutic systems for breast cancer treatment are discussed in this review. More significantly, the integration of CAP‐based medicine approaches with other breast cancer therapies, including chemo‐ and nanotherapy is thoroughly addressed.

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Canady Helios Cold Plasma Induces Breast Cancer Cell Death by Oxidation of Histone mRNA

Cited by 15 publications

References 85 publications

Canady Cold Helios Plasma Reduces Soft Tissue Sarcoma Viability by Inhibiting Proliferation, Disrupting Cell Cycle, and Inducing Apoptosis: A Preliminary Report

Canady Cold Helios Plasma Reduces Soft Tissue Sarcoma Viability by Inhibiting Proliferation, Disrupting Cell Cycle, and Inducing Apoptosis: A Preliminary Report

BCL2A1 regulates Canady Helios Cold Plasma-induced cell death in triple-negative breast cancer

Recent advances in cold atmospheric plasma (CAP) for breast cancer therapy

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