**4.3 Reactive oxygen species and its role in metastasis**

As explained earlier, the electrons which are not paired up usually have one or two-electron atoms in the shell, which is the outermost shell [93]. It is formed in the body in the form of products like reactive species of oxygen, nitrogen, sulfur, etc. It is formulated by the cytosol [94]. One aspect of it is to get the form of a radical one with unpaired electrons, and the other one without unpaired electrons of these species [95]. It is also a form of secondary messenger [93]. The general question arising here is why oxidative stress occurs, and the easiest way of approaching the solution is that there is a misbalanced proportion in the generation and detoxification of the species [31]. The activation of all phases of them is by several transcription factors like NF-B, activator proteins like in AP, and p53, where most mutations take place [93]. It works in both directions; that is, it works in the tumorigenic's favor as well as against the tumorigenic via signaling pathway of cancer MAPK/AP-1/NF- B and it also triggers inflammation cytokines, chemokine, etc. [93]. When there is an escalation of reactive species, there is an elevation in cancer cell division. Tumor cells require higher levels of reactive oxygen species as cancer cells prefer to proliferate in hypoxia conditions without even cell death. Reactive species have a vital role to play in metastasis and angiogenesis [93]. It also provides resistance to chemotherapy [32]. The category of transporter protein P-glycoproteins which is thereby also known as a multi-drug resistant, that work on moving out of particles "efflux" of cancer-inhibiting drugs from malignant cells [31].
