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 - 17/06/21
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Abstract |
The antitumor activity of the tea tree oil (TTO) derived product, Melaleuca Alternifolia Concentrate (MAC) was characterized mechanistically at the molecular and cellular level. MAC was analyzed for its anticancer activity against human prostate (LNCaP) and breast (MCF-7) cancer cell lines growing in vitro. MAC (0.02–0.06% v/v) dose-dependently induced the intrinsic (mitochondrial) apoptotic pathway in both the LNCaP and MCF-7 cell lines, involving increased mitochondrial superoxide production, loss of mitochondrial membrane potential (MMP), caspase 3/7 activation, as well as the presence of TUNEL+ and cleaved-PARP+ cell populations. At concentrations of 0.01–0.04% v/v, MAC caused cell cycle arrest in the G0/1–phase, as well as autophagy. The in vivo anticancer actions of MAC were examined as a treatment in the FVB/N c-Neu murine model for spontaneously arising breast cancers. Intratumoral MAC injections (1–4% v/v) significantly suppressed tumor progression in a dose-dependent manner and was associated with greater levels of tumor infiltrating neutrophils exhibiting anticancer cytotoxic activity. Induction of breast cancer cell death by MAC via the mitochondrial apoptotic pathway was also replicated occurring in tumors treated in vivo. In conclusion, our data highlights the potential for the Melaleuca-derived MAC product inducing anticancer neutrophil influx, supporting its application as a novel therapeutic agent.
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Highlights |
• | Malaleuca Alternifolia concentrate (MAC) has shown significant anticancer activity against human prostate and breast cancer cell lines. |
• | MAC promotes rapid mitochondrial superoxide production as oxidative stress, causing loss of mitochondrial transmembrane potential, leading to apoptosis. |
• | MAC caused autophagy in the cancer cells, cycle arrest in the G1 phase and treating breast tumors with MAC showed dose dependent regression. |
• | Tumor cell death by MAC via the mitochondrial apoptotic pathway was also replicated occurring in tumors in vivo. |
• | Intratumoral MAC led to recruitment of Gr-1+ tumor infiltrating neutrophils with potent cytotoxic activity against breast cancer cells. |
Abbreviations : AO, AVO, Ctrl, MAC, MFI, MMP, PARP, ROS, SEM, Sts, T4ol, TAN, TMRM, TPGS, TTO, TUNEL, Veh
Keywords : Melaleuca alternifolia concentrate, Cytotoxicity, Apoptosis, Breast cancer, Tumor infiltrating neutrophils
Plan
Vol 140
Article 111790- août 2021 Retour au numéro
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