Effect of Plasma-Activated Lactated Ringer’s Solution on Pancreatic Cancer Cells In Vitro and In Vivo

Sato, Yusuke; Yamada, Suguru; Takeda, Shigeomi; Hattori, Norifumi; Nakamura, Kae; Tanaka, Hiromasa; Mizuno, Masaaki; Hori, Masaru; Kodera, Yasuhiro

doi:10.1245/s10434-017-6239-y

Cited by 72 publications

(48 citation statements)

References 28 publications

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“…Therefore, as a method that can extensively reach cancer cells in the peritoneal cavity, we have devised PAM and conducted basic research to utilize PAM for clinical use as an indirect plasma therapy. Interestingly, our colleagues and we have demonstrated the anti-tumor effects of PAM against several types of cancer using an in vivo model of peritoneal metastasis 8,11,19 . These findings suggest that PAM may be a novel option for the treatment of peritoneal metastasis.…”

Section: Discussionmentioning

confidence: 96%

Plasma-activated medium promotes autophagic cell death along with alteration of the mTOR pathway

Yoshikawa

Liu

Nakamura

et al. 2020

Sci Rep

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the biological function of non-thermal atmospheric pressure plasma has been widely accepted in several types of cancer. We previously developed plasma-activated medium (pAM) for clinical use, and demonstrated that PAM exhibits a metastasis-inhibitory effect on ovarian cancer through reduced MMP-9 secretion. However, the anti-tumor effects of PAM on endometrial cancer remain unknown. In this study, we investigated the inhibitory effect of PAM on endometrial cancer cell viability in vitro.Our results demonstrated that AMEC and HEC50 cell viabilities were reduced by PAM at a certain PAM ratio, and PAM treatment effectively increased autophagic cell death in a concentration dependent manner. in addition, we evaluated the molecular mechanism of pAM activity and found that the mtoR pathway was inactivated by pAM. Moreover, our results demonstrated that the autophagy inhibitor MHY1485 partially inhibited the autophagic cell death induced by PAM treatment. These findings indicate that pAM decreases the viability of endometrial cancer cells along with alteration of the mtoR pathway, which is critical for cancer cell viability. collectively, our data suggest that pAM inhibits cell viability while inducing autophagic cell death in endometrial cancer cells, representing a potential novel treatment for endometrial cancer.Endometrial cancer is the most common gynecologic malignancy in Japan, with an estimated 13,600 new cases diagnosed in 2015 1 . The incidence of new cases is believed to have increased over the last few decades due to increased levels of obesity, hypertension, and diabetes mellitus, particularly in South Africa and several Asian countries including Japan 1,2 . Although the majority of endometrial cancer patients are diagnosed in the early stage and outcomes are generally favorable because of the typical symptom of irregular vaginal bleeding in women of menopausal age, the prognoses of patients in advanced stages not amenable to localized therapies remain poor 1 . Indeed, a frequent pattern of progression and recurrence is peritoneal metastasis, which is often resistant to systemic chemotherapy 3 . In addition, cytotoxic agents for endometrial cancer are relatively limited compared with other gynecologic malignancies. Thus, there is an increasing demand for novel approaches to peritoneal dissemination.For the past decade, nonequilibrium atmospheric pressure plasma (NEAPP) has been studied for its clinical applications such as sterilization, wound healing, and cancer therapy 4-6 . NEAPP represents a partially ionized gas with energy mainly accumulated as free electrons 7 . Recent studies have revealed that in addition to the direct irradiation of NEAPP to bacteria or tissues, indirect plasma treatment with plasma-activated medium (PAM) and plasma-activated lactate (PAL), which are activated by NEAPP, exhibit anti-tumor activity in several types of cancer, including ovarian, pancreatic, colorectal and gastric cancers 4,8-13 . The molecular mechanism of the anti-tumor effects triggered by PAM have been investigat...

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Section: Discussionmentioning

confidence: 96%

Plasma-activated medium promotes autophagic cell death along with alteration of the mTOR pathway

Yoshikawa

Liu

Nakamura

et al. 2020

Sci Rep

Self Cite

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“…In a xenograft mouse model, PAM inhibited the growth of ovarian and pancreatic cancer tumor cells [10,41]. Intraperitoneal injection of PAM/plasma-activated Ringer's lactate (PAL) inhibited the metastasis of ovarian, gastric, and pancreatic cancer tumors in disease model mouse experiments examining peritoneal metastasis [46][47][48]. However, in apoptosis induced by PAL, less ROS are produced in comparison with PAM [49], suggesting that components generated in PAM control the redox balance.…”

Section: Indirect Treatment: Pammentioning

confidence: 99%

New Hopes for Plasma-Based Cancer Treatment

Tanaka

Mizuno

Ishikawa

et al. 2018

Plasma

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“…This shows impressively how complex plasma chemistry is even in basic buffer solutions with only a few ingredients. The plasma‐treated Ringer's lactate solution reduced the viability of glioblastoma cells significantly and showed antitumor effects in vitro and in vivo …”

Section: Resultsmentioning

confidence: 99%

Pyruvate as a cell‐protective agent during cold atmospheric plasma treatment in vitro: Impact on basic research for selective killing of tumor cells

Bergemann

Rebl

Otto

et al. 2019

Plasma Processes & Polymers

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Promising investigations on the selective killing of tumor cells were reported using cold atmospheric pressure plasma (CAP) in vitro. Pyruvate, a supplement in cell culture media, could protect cells against the action of reactive oxygen species. Here, we provide an overview of the in vitro studies concerning the selective killing of tumor cells by CAP with special emphasis on pyruvate concentration in the cell culture media. Several former studies were performed in media with different pyruvate content. Our cell experiments confirmed that pyruvate mitigates the action of the plasma‐activated medium on cells. Therefore, future in vitro studies should be done in media with similar pyruvate content.

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Effect of Plasma-Activated Lactated Ringer’s Solution on Pancreatic Cancer Cells In Vitro and In Vivo

Abstract: Our study demonstrated the antitumor effects of PAL in vitro and in vivo. Intraperitoneal administration of PAL may be a novel therapeutic option for peritoneal metastases.

Cited by 72 publications

References 28 publications

Plasma-activated medium promotes autophagic cell death along with alteration of the mTOR pathway

Plasma-activated medium promotes autophagic cell death along with alteration of the mTOR pathway

New Hopes for Plasma-Based Cancer Treatment

Pyruvate as a cell‐protective agent during cold atmospheric plasma treatment in vitro: Impact on basic research for selective killing of tumor cells

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