Abstract
The chemotherapy drug doxorubicin (DOX) is effective in treating many types of cancers. However, due to its pro-inflammatory and cardiotoxic side effects, other remedies have also been explored as alternative treatments. The plant Alangium longiflorum was reported to contain cytotoxic activity against cancer cells, but it is unclear whether this plant would also yield side effects similar to doxorubicin. Hence, this study investigated cytotoxic activity of A. longiflorum leaf extract against lung cancer cells and compared its pro-inflammatory and cardiotoxic side effects with those of DOX. Methods:Cytotoxic activity of A. longiflorum in human lung (A549) and breast (MCF-7) cancer cells was initially assessed by MTT assay and then was compared with doxorubicin. Presence of secondary metabolites in the leaf extract was examined by phytochemical screening. The ability of the plant extract to induce apoptosis was determined by measuring caspase-3/7 activity and apoptosis-related gene expression. Pro-inflammatory response was assessed by quantifying NFκB transcriptional activity and nuclear translocation with dual luciferase reporter and immunofluorescence assays, respectively. Cardiotoxicity was measured using zebrafish as a model organism. Results: A. longiflorum leaf extract displayed high cytotoxic activity against A549 versus MCF-7, which led this study to focus further on A549. Phytochemical screening showed that the extract contained terpenoids, alkaloids, phenols, cardiac glycosides, and tannins. The extract induced apoptosis through activation of caspase-3/7 and upregulation of pro-apoptotic genes without causing NFκB transcriptional activation and nuclear localization. The extract also did not significantly reduce heart function in zebrafish. Conclusion:Overall, our data suggested that extract from leaves of A. longiflorum can have the potential to serve as apoptotic agent towards lung cancer without inducing significant cardiotoxicity.
Highlights
IntroductionChemotherapy drugs, such as doxorubicin (DOX), induce cell death (apoptosis) or permanent growth arrest (cellular senescence) in cancer cells (Gonzalez et al, 2016)
Chemotherapy drugs, such as doxorubicin (DOX), induce cell death or permanent growth arrest in cancer cells (Gonzalez et al, 2016)
DOX displayed cytotoxic activity towards A549 and MCF-7 at an LC50 of 4.67μg/ml and 5.62μg/ml, respectively, (Figure 1C, Table 2), suggesting that the drug had a similar efficacy with AL in inducing cytotoxicity within 24h (p = 0.3336)
Summary
Chemotherapy drugs, such as doxorubicin (DOX), induce cell death (apoptosis) or permanent growth arrest (cellular senescence) in cancer cells (Gonzalez et al, 2016). Alangium longiflorum (Family: Alangiaceae), commonly known as Malatapai, is found in Borneo and the Philippines (Sosef et al, 1998). It is listed as vulnerable on the IUCN Red List (World Conservation Monitoring Centre, 1998). This plant belongs to the genus Alangium, which contains several species used in traditional medicine. A. longiflorum displayed notable cytotoxicity against U251 glioma cells by inhibiting transcriptional activity of hypoxia-induced factor (HIF1), which is activated during hypoxic conditions (Klausmeyer et al, 2008). The alkaloid demethylcephaeline from the stem bark of the plant exhibited potent cytotoxicity against A549 lung and MCF-7 breast cancer cell lines
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