Abstract
Cancer remains one of the leading causes of death globally. According to the World Health Organization, the annual cancer cases globally are expected to reach 24 million by 2035. In 2018, the cancer mortality rate was over 50 % from a South African sample of 107 467 cancer diagnoses reported according to reports by WHO in association with GLOBOCAN. Melanoma is the most prevalent type of skin cancer in people who have fair skin, accounting for 80% of deaths from skin lesions with a late presentation. Cervical cancer is considered one of the most prevalent among gynaecological cancers in developing countries. In 2018, it claimed the lives of over 300 000 women worldwide. The increasing number of women dying due to this cancer globally, has been attributed to the lack of access to healthcare in low-income countries. One in every 42 women in South Africa has a lifetime risk of getting cervical cancer. A melanoma treatment with cisplatin seemed effective, however it was found to be associated with irreparable DNA damage whereas most current treatments are either ineffective or possess unbearable side effects. This study aimed to investigate the cytotoxic effects of Leptospermum petersonii on melanoma and cervical cancer cells and isolate the possible bioactive compound(s). L. petersonii is known to have antimicrobial properties. It is believed that its leaves contain ursolic acid and essential oils, which can inhibit the growth of fungi. Its methanolic extract has been shown to be more potent than the commonly used ampicillin against certain bacteria. However, there is no previous report about this plant on cancer. Sequential extraction was perfomed using hexane, ethyl acetate, and methanol. Both the ethyl acetate and methanol extracts showed to possess a significant potency against a375 and me-180 cells. The compound 6-methyltectochrysin was successfully isolated from the methanolic extract of L. petersonii, and it showed higher activity on melanoma than on cervical cancer cells. Caspase Glo 3/7 assay and annexin-V FITC - PI apoptotic assays were carried on after treatment with 6-methyltectochrysin. These validated induction of apoptosis in me-180 and a375 cells treated with 6-methyltectochrysin. Further investigation of the relative expression of several apoptotic genes in a375 cells showed an upregulation of the pro-apoptotic Bax and a downregulation of BCL2. TP53 was found to be downregulated and RBBP6, its negative regulator was upregulated. Further studies will be needed to identify molecular pathways and targets of the compound 6-methyltectochrysin in melanoma cells.
Keywords: Apoptosis, Leptospermum petersonii, Cytotoxicity, Melanoma, Caspase Crude extract