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Old dog, new trick: Trivalent arsenic as an immunomodulatory drug.

ABSTRACT: Trivalent arsenic (As(III)) is recently found to be an immunomodulatory agent. As(III) has therapeutic potential in several autoimmune and inflammatory diseases in vivo. In vitro, it selectively induces apoptosis of immune cells due to different sensitivity. At a non-toxic level, As(III) shows its multifaceted nature by inducing either pro- or anti-inflammatory functions of immune subsets. These effects are exerted by either As(III)-protein interactions or as a consequence of As(III)-induced homeostasis imbalance. The immunomodulatory properties also show synergistic effects of As(III) with cancer immunotherapy. In this review, we summarize the immunomodulatory effects of As(III), focusing on the effects of As(III) on immune subsets in vitro, on mouse models of immune-related diseases, and the role of As(III) in cancer immunotherapy. Updates of the mechanisms of action, the pioneer clinical trials, dosing, and adverse events of therapeutic As(III) are also provided.

SUBMITTER: Ye Y

PROVIDER: S-EPMC7174890 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveThere is increasing pre-clinical and clinical evidence that metformin, a commonly used diabetes medication, has a protective effect in cancer. The aim of this review is to discuss metformin's anti-cancer molecular mechanisms of action and to summarize the current literature demonstrating metformin's potential in gynecologic cancer prevention and treatment.MethodsA PubMed search was conducted combining the keywords "metformin" with "neoplasm", "uterine neoplasms", "ovarian neoplasms", and "uterine cervical neoplasms". Studies published in English between 1994 and 2014 were included.ResultsPre-clinical studies in endometrial, ovarian, and cervical cancer suggest that metformin inhibits the growth of cancer cells. The primary molecular mechanism mediating this effect appears to be the activation of AMP-activated protein kinase (AMPK) and the subsequent inhibition of mammalian targets of rapamycin (mTOR). The pre-clinical findings are augmented by clinical studies indicating that metformin use is associated with a reduced risk of cancer and improved survival in diabetic women with ovarian and endometrial cancers. No clinical analyses have evaluated metformin use and cervical cancer. Overall, the data showing a favorable effect of metformin is strongest for endometrial and ovarian cancer and prospective clinical testing is ongoing in these two malignancies.ConclusionsNumerous clinical studies have reported an association between metformin use by diabetic patients and improved outcomes in gynecologic cancers. In addition, pre-clinical reports have identified plausible biological mechanisms to explain the molecular mechanism of action of metformin in cancer. However, the most important question remains unanswered: Will metformin be effective against cancer in patients without diabetes? Until this question is answered with prospective clinical testing, the role of metformin in the treatment or prevention of gynecologic malignancies remains theoretical and the clinical use of metformin as a cancer therapeutic is experimental.

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Old dog, new trick: Trivalent arsenic as an immunomodulatory drug.

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