Abstract
Phyllanthus muellerianus (PM) and Ficus exasperata (FE) are plants used against cancers. We evaluated the phytochemical profiles and in vitro antioxidant potentials of PM and FE, and investigate their effects on cell proliferation, intracellular calcium ([Ca2+]i), caspases 3/9, apoptosis, oxidative stress markers, and Bax/cytochrome C expression in PC-3 cells. The phytochemical profiles were evaluated by liquid chromatography-mass spectrometry (LC‐MS), and the antioxidant by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals scavenging method. The cells were incubated for 24 h with 3% tween 80, paclitaxel (5 nM), PM (800 and 1200 µg/ml), and FE (800 and 1200 µg/ml). After treatments, [Ca2+]i, caspases 3/9, apoptosis and oxidative stress parameters were measured using colorimetric kits, while the mRNA levels of Bax and cytochrome C were quantified by RT‐qPCR. Nitidine, phloridzin and linoleic acid were identified in PM, while docosane, cardanol and chlorogenic acid were revealed in FE. The in vitro antioxidant potential of PM was greater than that of FE. Both plants inhibited the growth of PC-3 cells in a dose-dependent manner, but significantly (p < 0.5–0.001) increased [Ca2+]i, apoptosis level, caspase 3/9 activities, reactive oxygen species production and lipid peroxidation, compared with control. Moreover, the activities of superoxide dismutase, catalase and glutathione peroxidase were significantly decreased in the cells incubated with the plant extracts, PM being the most effective. Paclitaxel, PM and FE upregulated Bax and cytochrome C genes in PC-3 cells. PM and FE inhibited the growth of PC-3 cells by modulating the [Ca2+]i and inducing apoptosis through Bax/Cytochrome C/Caspase 3–9 signaling pathway.
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Abbreviations
- Bax:
-
Bcl-2-associated X protein
- CAT:
-
Catalase
- CHPx:
-
Cumene hydroperoxide
- DHR:
-
123, Dihydrorhodamine‐123
- DMSO:
-
Dimethyl sulfoxide
- DPPH:
-
2,2-Diphenyl-1-picrylhydrazyl
- EGTA:
-
Ethylene glycol‐bis(2‐aminoethyl‐ ether)‐N,N,N′,N′‐tetraacetic acid
- FBS:
-
Fetal bovine serum
- GSH-Px:
-
Glutathione peroxidase
- MDA:
-
Malondialdehyde
- MTT:
-
3‐(4,5‐Di‐methylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide
- PSA:
-
Prostate-specific antigen
- ROS:
-
Reactive oxygen species
- RPMI:
-
Roswell Park Memorial Institute medium
- SOD:
-
Superoxide dismutase
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Acknowledgements
Financial support from C V Raman International Fellowship for African Researchers (INT/NAI/CVRF/2016 dated 24 October 2016) is greatly acknowledged. Sincere thanks to Sathyabama Institute of Science and Technology, Chennai for the research facilities. The authors acknowledge the Mass spectrometry facility, IOE, University of Mysore, Manasagangotri, Mysore for providing the LC-MS facilities.
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This work was supported by CV Raman (Ref: INT/NAI/CVRF/2016) and Sathyabama Institute of Science and Technology, Chennai, India.
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PBDD and VV participated in the study conception and conducted the experimental research. PBDD, MA, KA and GK participated in the data interpretation, data analysis and statistical analysis for the variables. PBDD, NSN, PW and VV drafted the paper. PBDD and VV were responsible for the overall supervision. All co-authors read and approved the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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Deeh, P.B.D., Arumugam, M., Alagarsamy, K. et al. Phyllanthus muellerianus and Ficus exasperata exhibit anti-proliferative and pro-apoptotic activities in human prostate cancer PC-3 cells by modulating calcium influx and activating caspases. Biologia 77, 1981–1994 (2022). https://doi.org/10.1007/s11756-022-01065-z
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DOI: https://doi.org/10.1007/s11756-022-01065-z