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J Microbiol Biotechnol
2021 Jun 28;316:775-783. doi: 10.4014/jmb.2103.03034.
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Methanolic Extract from Sea Cucumber, Holothuria scabra, Induces Apoptosis and Suppresses Metastasis of PC3 Prostate Cancer Cells Modulated by MAPK Signaling Pathway.
Pranweerapaiboon K
,
Noonong K
,
Apisawetakan S
,
Sobhon P
,
Chaithirayanon K
.
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Sea cucumber, Holothuria scabra, is a well-known traditional Asian medicine that has been used for suppressing inflammation, promoting wound healing, and improving immunity. Moreover, previous studies demonstrated that the extract from H. scabra contains many bioactive compounds with potent inhibitory effect on tumor cell survival and progression. However, the effect of the methanolic extract from the body wall of H. scabra (BWMT) on human prostate cancer cells has not yet been investigated. In this study, we aimed to investigate the effects and underlying mechanism of BWMT on prostate cancer cell viability and metastasis. BWMT was obtained by maceration with methanol. The effect of BWMT on cell viability was assessed by MTT and colony formation assays. The intracellular ROS accumulation was evaluated using a DCFH-DA fluorescence probe. Hoechst 33342 staining and Annexin V-FITC/PI staining were used to examine the apoptotic-inducing effect of the extract. A transwell migration assay was performed to determine the anti-metastasis effect. BWMT significantly reduced cell viability and triggered cellular apoptosis by accumulating intracellular ROS resulting in the upregulation of JNK and p38 signaling pathways. In addition, BWMT also inhibited the invasion of PC3 cells by downregulating MMP-2/-9 expression via the ERK pathway. Consequently, our study provides BWMT from H. scabra as a putative therapeutic agent that could be applicable against prostate cancer progression.
Fig. 1. BWMT inhibits cell viability of advanced stage of prostate cancer cell line.(A) Cells viability was examined by MTT assay after treatment with 0-100 μg/ml BWMT for 24 and 48 h. (B) Cells were treated with 15, 30, and 60 μg/ml BWMT to observe the long-term cytotoxic effect (14 days) by colony formation assay. Colonies were stained with crystal violet and observed under a microscope. The bar graph is presented as mean ± SD. *p < 0.05, significant difference compared with control group. The experiments were performed independently for 3 times.
Fig. 2. BWMT promoted intracellular ROS accumulation in PC3 cells.The amount of ROS generation in each group was calculated as percentage of fluorescence intensity relative to the control. Data are expressed as mean ± SD from three independent experiments (*p < 0.05).
Fig. 3. The cell cycle distributions of PC3 after treatment with the designated concentrations of BWMT.Data were expressed as mean ± SD from three experiments (*p < 0.05).
Fig. 4. The effects of BWMT on apoptosis induction in prostate cancer cells.(A) Nuclear morphology of Hoechst 33342 staining nuclei of BWMT-treated prostate cancer cells. Asterisks indicate nuclei condensation. (B) Rate of PC3 apoptosis analyzed by Annexin V-FITC/PI dual-labeling and flow cytometry. (C) Western blotting evaluated the effect of BWMT on apoptotic markers expressions. Data were expressed as mean ± SD from three experiments (*p < 0.05).
Fig. 5. Inhibition of migration and invasion of prostate cancer cells by BWMT.(A) PC3 cells were treated with the designated concentrations of BWMT and placed on an upper chamber coated with Matrigel. Cells that migrated and invaded to the lower chamber were stained with crystal violet and observed under a microscope. (B) The western blot revealed the effects of BWMT on the expressions of invasion markers MMP-2 and MMP-9. Data were expressed as mean ± SD from three experiments (*p < 0.05).
Fig. 6. The effects of BWMT on MAPK pathways (A) JNK, (B) p38, and (C) ERK.The band intensities of p-JNK, pp38, and p-ERK were normalizing with the JNK, p38, and ERK from three experiments.
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