Tea tree oil extract causes mitochondrial superoxide production and apoptosis as an anticancer agent, promoting tumor infiltrating neutrophils cytotoxic for breast cancer to induce tumor regression

Intratumoral pro-oxidants promote cancer immunotherapy by recruiting and reprogramming neutrophils to eliminate tumors

“…The problem with most of the clinical studies has been that neutrophils are a divergent population of immune cell types and many of these cancer studies have tended to lump them together without considering the differences in the subtypes that exist within the neutrophil population. Our recent studies with murine models of breast cancer (syngeneic, spontaneously developing ductal carcinoma in situ) have shown that when an appropriate potent pro-oxidant is delivered intratumorally, the right type of anticancer neutrophils are recruited to the site of the tumor [ 13 ]. For example, we showed that breast tumors given an intratumoral injection of a pro-oxidant treatment prepared from tea tree oil (TTO) promoted neutrophil infiltration and acted as potent cytotoxic anticancer agents that considerably suppressed tumor growths, to the point of remission [ 13 ].…”

“…Our recent studies with murine models of breast cancer (syngeneic, spontaneously developing ductal carcinoma in situ) have shown that when an appropriate potent pro-oxidant is delivered intratumorally, the right type of anticancer neutrophils are recruited to the site of the tumor [ 13 ]. For example, we showed that breast tumors given an intratumoral injection of a pro-oxidant treatment prepared from tea tree oil (TTO) promoted neutrophil infiltration and acted as potent cytotoxic anticancer agents that considerably suppressed tumor growths, to the point of remission [ 13 ]. Our studies are not unique and many other studies specifically applying intratumoral pro-oxidant agents such as hydrogen peroxide (H2O2) to promote anticancer tumor-associated neutrophils (TANs) contributed as the major focus of this review.…”

“…The action of the pro-oxidant induced ROS as a triggering mechanism is most likely responsible for the activated neutrophil recruitment and response that was obtained by the potent pro-oxidant tea tree oil (TTO) preparation when given as intratumoral injections into breast tumors [ 13 ]. Consequently, the number of neutrophils infiltrating into the tumors greatly increased by up to tenfold.…”

“…These LDNs isolated from the TTO-treated tumors were identified via their surface marker expression to be CD11b + , Ly6G hi , Gr1 + N1 neutrophils and were the predominant immune cells infiltrating into the treated breast tumors. Furthermore, analysis of tumor sections showed marked and extensive increased presence of Gr-1 + immunostaining adjacent to TUNEL + regions indicative of cell death in the treated but not in the control untreated tumors [ 13 ].…”

Anti-Cancer Properties of Coix Seed Oil against HT-29 Colon Cells through Regulation of the PI3K/AKT Signaling Pathway

“…Natural plant products have attracted increasing attention in cancer treatment due to their low side effects and high efficacy [3]. For instance, dark sweet cherry phenolics, curcumin, isoflavonoids, resveratrol, epigallocatechin gallate (EGCG), tea tree oil extract, corn oil, and isoliquiritigenin (ISL) can be used for cancer therapy and to help reverse the drug resistance of certain cancer cells [4][5][6][7][8][9][10][11]. Accordingly, many works have explored the protective effect of natural sources to inhibit cancer cells.…”