**1. Arsenic in cancer treatment**

Arsenic, one of the ancient drugs, is currently used as a therapeutic agent worldwide because of its substantial anticancer activity. Arsenic trioxide (ATO), a trivalent arsenite (AsIII), was initially used for the treatment of chronic myelogenous leukemia (CML) in the nineteenth century [1]. ATO readily induces apoptosis by promoting differentiation of acute promyelocytic leukemia (APL) cells and is thereby utilized as a therapeutic drug in the clinical setting [2]. ATO is currently used to treat patients with APL and recurrent/relapsed multiple myeloma (MM) [3]. Numerous studies that examined the tumor suppressive and/or proapoptotic effect

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

of ATO have revealed the molecular mechanism by which ATO exerts an anticancer effect in both solid cancer and hematological malignancies (see below section). Thus, accumulating evidence implicates ATO and/or other arsenicals in clinical use as a promising drug to treat cancer patients. Besides ATO monotherapy, there is a growing body of evidence that ATO may be a favorable drug when combined with not only conventional anticancer therapeutics including radiation and chemotherapy but also recently developed molecular-targeted drugs. In one example, the combined treatment of all-*trans*-retinoic acid (ATRA) with ATO has been shown to synergistically induce apoptosis of APL cells and clinically shown to be better outcome and less toxicity than the combined treatment of ATRA with chemotherapy in the treatment of patients with APL [4, 5]. This chapter summarizes the anticancer effect of ATO-based combination therapies in different types of solid cancer and hematological malignancies. Furthermore, the molecular mechanism by which ATO-based combination therapies exert a proapoptotic effect in cancer cells is discussed.
