Search efficiency and lesser side effects has been

Search for a new anticancer therapeutics withbetter efficiency and lesser side effects has been continued because of thelarge number of mortality and poor prognosis in cancer patients. Naturalproducts are becoming an integral component of drug discovery  in cancer research, and approximately 60% ofclinically approved anticancer drugs are from secondary metabolites found innature. Several epidemiological and case-control studies have been reportedthat plant based agents act as an anticancer drug against a variety of cancerand associated with positive health outcomes.

In this study, we have evaluatedthe anticancer potential of AP, a naturally occurring monoterpenes of essentialoil against human skin cancer. AP treatment increased ROS generation in skincancer cells. Further, we noticed thatAP induces loss of mitochondrial membrane potential in A431 and A375 cells in aconcentration dependent manner. Similarly, Pavithra et al., (2017) found thatessential oils  induces cell deaththrough intrinsic (mitochondrial) mediated apoptosis in A431 predominantlymediated by inducing ROS. In our study, the AP mediated generation ofROS  promoted the dissipation ofmitochondrial membrane potential, which ultimately leads to leakage of proapoptotic factors finally apoptosis.

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In a same way, Matsuo et al., (2011)clearly demonstrated that AP specifically damages the outer mitochondrialmembrane by employing cyclosporin A, a potent inhibitor of the inner mitochondrialpermeability transition pore along with AP to study anti metastatic protection in a melanoma model. Hence, wehypothesize that essential oil like AP can easily disrupt and permeabilize themitochondrial membrane, thereby change electron flow through the electrontransport chain and produce free radicals (Bakkali et al., 2008)Recently, phytochemicals are largely used either  chemotherapeutic or chemopreventive agentsthat act via different mechanisms such as antioxidants, modulator of geneexpression and signal transduction pathways. In our study, we noticed that APinduced single strand DNA break in break in skin cancer cells. This is may bedue to the increased generation of ROS and mitochondrial damage. Further,results from the immunofluroscence of gamma-H2AX in skin cancer cells clearlyindicate that AP can also induce the double strand break. It is well known thatmost of the clinical cancer drug induces DNA damage by directly or indirectlyfor example cissplatin and  doxorubicin.

Similarly, 1,8-cineol, a monoterpene induced oxidative DNA damage andsubsequent DNA double- strand breaks in the hamster cell lines in a significantconcentration-dependent manner (Dörsam et al., 2015). Hinokitiol, a similarmonoterpene induces DNA damage in gefitinib-resistant lung adenocarcinoma cells(Li et al., 2014). It is documented that DNA double-strand breaks interfereswith cell cycle by blocking the replication fork succession consequentiallyinduce cell death. Additionally,  inorder to confirm the molecular mechanisms of AP induced apoptosis in skincancer cells, we performed TUNEL assay. We found that AP induces the apoptosisvia DNA damage in a concentration dependent manner. In conclusion, AP inducesdirect as well as indirect DNA damage mediated apoptosis in A431 and A375 skincancer cells in a concentration dependent manner.