Phyllanthus is an herbal medicine that is widely used in China, India and South Africa for its various biological activities, including anti-hepatitis, antibacterial, and anti-cancer properties. The anti-cancer effect of this plant has been studied by different groups in different cancer types.
The water extract of phyllanthus has been reported to significantly reduce the viability of cancer cell lines from different origins. Furthermore, this extract suppressed tumor development in mice implanted with Lewis lung carcinoma cells.
It has been proposed that phyllanthus' anti-cancer activity could be due to apoptosis induction in cancer cells, verified by DNA fragmentation test and an increased activity of Capspase-3 via both intrinsic and extrinsic pathways.
On the other hand, its anti-cancer effect has been partially linked to a down-regulation of telomerase activity and an induction of apoptotic pathway. In addition, anti-angiogenic activity has been also reported for this herbal medicine, mediated through suppression of matrix metalloproteinase 2 (MMP-2) secretion and activity.
A group of researchers have investigated the anti-cancer effect of Phyllanthus on human prostate carcinoma in 2013. They reported a significant decrease in Wnt, NF-κB, Myc/Max, MAPK/ERK, and MPK/JNK in PC-3 cells, following their treatment with phyllanthus extract.
Several other signaling molecules were also affected, including Pan-Ras, c-Raf, RSK, ELK1, c-Jun, JNK1/2, P38 MAPK, c-Myc, DSH, β-Catenin, AKT, HIF-1α, and VEGF. They verified 72 differentially-expressed proteins in treated PC-3 cells that were involved in tumor cell adhesion, apoptosis, glycogenesis, glycolysis, metastasis, angiogenesis, protein synthesis and energy metabolism.
In the human melanoma (MeWo) cancer cell line, five different cancer-related signaling pathways have been reported to be altered in effect of phyllanthus extract treatment in MeWo cells, including NF-κB, Myc/Max, Hypoxia, MAPK/ERK, and MAPK/JNK.
A down-regulation of Pan-Ras, c-Raf, RSK, phospho-Elk1, c-Myc, AKT, HIF-1α, Bcl-2, and VEGF, and an up-regulation of Bax, pjospho-JNK1/2, and phospho-GSK3β intracellular signaling molecules were detected in Western blot analysis.
Proteomics-based approaches highlighted a total of 52 differentially expressed proteins involved in apoptosis, glycogenesis, glycolysis, angiogenesis, protein synthesis, energy metabolism, tumor growth and metastasis.
Another group studied the effect of phyllanthus on human lung cancer cell line (A549). They reported anti-metastatic activities through ERK1/2 pathway by Raf protein suppression. This in turn could cause the suppression of MMP7 and MMP9 expression, which results in an interruption in metastasis.
Furthermore, researchers reported an inhibitory effect on hypoxia pathway by HIF-1α inhibition, which caused a reduced VEGF and iNOS expression. Proteomics analysis also showed a downregulation of several proteins in charge of metastatic processes, transcriptional proteins, antiapoptotic proteins, ad glycolytic enzymes.
Finally, another group of researchers has verified the cytotoxic properties of phyllanthus in the PC-3 and MeWo human cancer cells. The same treatment did not show any significant cytotoxicity in the normal human skin (CCD-1127SK) and prostate (RWPE-1) cells.
They concluded that this cytotoxic activity was mediated through apoptosis induction with minimal necrotic effects. Furthermore, G0/G1- and S-phase cell cycle arrest were confirmed for prostate and skin cells, which led in cell accumulation in sub-G1 (apoptosis) phase.
Overall, the recent findings could suggest phyllanthus interference with multiple tumorigenesis signaling pathways, which makes it a good therapeutic candidate for cancer treatment.
