Materials and Methods: A systematic review of the existing literature was conducted using the following search terms: ‘melatonin’, ‘X-ray irradiation’, ‘charged particle irradiation’, ‘carbon ion irradiation’, ‘mitochondria’, ‘apoptosis’ and ‘cancer cells’. The search used PubMed and spanned the period from January 2000 to April 2018. 

Results: The impact of melatonin on mitochondria of cancer cells consisted of ‘Melatonin antiproliferative effects require active mitochondrial function in embryonal carcinoma cells’, ‘Human transporters, PEPT1/2, facilitate melatonin transportation into mitochondria of cancer cells: An implication of the therapeutic potential’, ‘Melatonin increases human cervical cancer HeLa cell apoptosis induced by cisplatin via inhibition of JNK/Parkin/mitophagy axis’ and ‘Combination of melatonin and rapamycin therapy for head and neck cancer: Suppression of AKT/mTOR pathway activation, and promotion of mitophagy and apoptosis via mitochondrial function regulation’. The impact of carbon ion irradiation on mitochondria of cancer cells consisted of ‘Carbon ion beams induce hepatoma cell death by NADPH oxidase-mediated mitochondrial damage’, ‘MEK-ERK-dependent multiple caspase activation by mitochondrial proapoptotic Bcl-2 family proteins is essential for heavy ion irradiation-induced glioma cell death’, ‘Fragmentation level determines mitochondrial damage response and subsequently the fate of cancer cells exposed to carbon ion irradiation’ and ‘Carbon ion beam triggers both caspase-dependent and caspase-independent pathway of apoptosis in HeLa and status of PARP-1 controls intensity of apoptosis’. 

Conclusion: Mitochondria are the promising therapeutic targets for cancer treatments in relation to melatonin and carbon ion irradiation. Further preclinical and clinical investigations are indispensable in order to develop innovative anticancer agents.