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Apoptosis-Inducing Activity of Marine Sponge Haliclona sp. Extracts Collected from Kosrae in Nonsmall Cell Lung Cancer A549 Cells.

Bae W, Lim HK, Kim KM, Cho H, Lee SY, Jeong CS, Lee HS, Jung J - Evid Based Complement Alternat Med (2015)

Bottom Line: Further, methanol extracts of Haliclona sp. significantly inhibited cell proliferation and cell viability.A549 cells treated with Haliclona sp. demonstrated induced expression of c-Jun N-terminal kinase (JNK), p53, p21, caspase-8, and caspase-3.The percentage of apoptotic cells significantly increased in A549 cultures treated with Haliclona sp.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Duksung Women's University, Seoul 132-714, Republic of Korea.

ABSTRACT
Although various anticancer drugs have been developed for the treatment of nonsmall cell lung cancer, chemotherapeutic efficacy is still limited. Natural products such as phytochemicals have been screened as novel alternative materials, but alternative funds such as marine bioresources remain largely untapped. Of these resources, marine sponges have undergone the most scrutiny for their biological activities, including antiinflammatory, antiviral, and anticancer properties. However, the biological mechanisms of the activities of these marine sponges are still unclear. We investigated the anticancer activity of marine sponges collected from Kosrae in Micronesia and examined their mechanisms of action using nonsmall cell lung cancer A549 cells as a model system. Of 20 specimens, the Haliclona sp. (KO1304-328) showed both dose- and time-dependent cytotoxicity. Further, methanol extracts of Haliclona sp. significantly inhibited cell proliferation and cell viability. A549 cells treated with Haliclona sp. demonstrated induced expression of c-Jun N-terminal kinase (JNK), p53, p21, caspase-8, and caspase-3. The percentage of apoptotic cells significantly increased in A549 cultures treated with Haliclona sp. These results indicate that Haliclona sp. induces apoptosis via the JNK-p53 pathway and caspase-8, suggesting that this marine sponge is a good resource for the development of drugs for treatment of nonsmall cell lung cancer.

No MeSH data available.


Related in: MedlinePlus

Haliclona sp. extract induces the expression of proteins related to the JNK and extrinsic apoptotic pathway. A549 cells were treated with Haliclona sp. extract for 48 h. (a) Protein levels were determined using Western blotting. (b) Protein bands were analyzed by ImageJ software. The data were calculated by the ratio of each to β-actin bands (as corresponding bands).
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fig5: Haliclona sp. extract induces the expression of proteins related to the JNK and extrinsic apoptotic pathway. A549 cells were treated with Haliclona sp. extract for 48 h. (a) Protein levels were determined using Western blotting. (b) Protein bands were analyzed by ImageJ software. The data were calculated by the ratio of each to β-actin bands (as corresponding bands).

Mentions: To investigate the cellular mechanism of Haliclona sp. extract, protein levels were analyzed using Western blots. Specifically, we examined the apoptosis-inducing factors of JNK, p53, Bax, caspase-3, caspase-8, and caspase-9 which activate the mitochondrial or intrinsic apoptotic pathway [15]. JNK phosphorylates and regulates the activity of p53 and its stability [16–18]. The p53 tumor suppressor gene plays an important role in cell cycle, DNA repair, replicative senescence, and cell death [19]. As shown in Figure 5, A549 cells treated with Haliclona sp. extracts displayed significantly increased levels of JNK and p53 proteins, as well as p21 a downstream gene upregulated by p53. In several studies, the JNK-p53 pathway was also reported as one of the apoptotic pathways induced by natural products [16, 20]. However, levels of markers of the intrinsic apoptosis pathway, Bax and caspase-9, were not changed by Haliclona sp. extracts. Interestingly, the markers of extrinsic apoptosis pathway, caspase-8 and caspase-3, were increased by Haliclona sp. extracts. The results suggest that Haliclona sp. extracts activate JNK and caspase-8, thereby activating the apoptotic pathway and inhibiting cell viability and proliferation. Still, Haliclona sp. extract remained to be determined regarding the upper stream of JNK and caspase-8. Several studies reported the relationship between JNK and caspase-8 induced apoptosis [21–23]. TRAIL death receptor activates caspase-8 and also JNK [21–23]. It may influence the anticancer effect of Haliclona sp. extract.


Apoptosis-Inducing Activity of Marine Sponge Haliclona sp. Extracts Collected from Kosrae in Nonsmall Cell Lung Cancer A549 Cells.

Bae W, Lim HK, Kim KM, Cho H, Lee SY, Jeong CS, Lee HS, Jung J - Evid Based Complement Alternat Med (2015)

Haliclona sp. extract induces the expression of proteins related to the JNK and extrinsic apoptotic pathway. A549 cells were treated with Haliclona sp. extract for 48 h. (a) Protein levels were determined using Western blotting. (b) Protein bands were analyzed by ImageJ software. The data were calculated by the ratio of each to β-actin bands (as corresponding bands).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4508479&req=5

fig5: Haliclona sp. extract induces the expression of proteins related to the JNK and extrinsic apoptotic pathway. A549 cells were treated with Haliclona sp. extract for 48 h. (a) Protein levels were determined using Western blotting. (b) Protein bands were analyzed by ImageJ software. The data were calculated by the ratio of each to β-actin bands (as corresponding bands).
Mentions: To investigate the cellular mechanism of Haliclona sp. extract, protein levels were analyzed using Western blots. Specifically, we examined the apoptosis-inducing factors of JNK, p53, Bax, caspase-3, caspase-8, and caspase-9 which activate the mitochondrial or intrinsic apoptotic pathway [15]. JNK phosphorylates and regulates the activity of p53 and its stability [16–18]. The p53 tumor suppressor gene plays an important role in cell cycle, DNA repair, replicative senescence, and cell death [19]. As shown in Figure 5, A549 cells treated with Haliclona sp. extracts displayed significantly increased levels of JNK and p53 proteins, as well as p21 a downstream gene upregulated by p53. In several studies, the JNK-p53 pathway was also reported as one of the apoptotic pathways induced by natural products [16, 20]. However, levels of markers of the intrinsic apoptosis pathway, Bax and caspase-9, were not changed by Haliclona sp. extracts. Interestingly, the markers of extrinsic apoptosis pathway, caspase-8 and caspase-3, were increased by Haliclona sp. extracts. The results suggest that Haliclona sp. extracts activate JNK and caspase-8, thereby activating the apoptotic pathway and inhibiting cell viability and proliferation. Still, Haliclona sp. extract remained to be determined regarding the upper stream of JNK and caspase-8. Several studies reported the relationship between JNK and caspase-8 induced apoptosis [21–23]. TRAIL death receptor activates caspase-8 and also JNK [21–23]. It may influence the anticancer effect of Haliclona sp. extract.

Bottom Line: Further, methanol extracts of Haliclona sp. significantly inhibited cell proliferation and cell viability.A549 cells treated with Haliclona sp. demonstrated induced expression of c-Jun N-terminal kinase (JNK), p53, p21, caspase-8, and caspase-3.The percentage of apoptotic cells significantly increased in A549 cultures treated with Haliclona sp.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Duksung Women's University, Seoul 132-714, Republic of Korea.

ABSTRACT
Although various anticancer drugs have been developed for the treatment of nonsmall cell lung cancer, chemotherapeutic efficacy is still limited. Natural products such as phytochemicals have been screened as novel alternative materials, but alternative funds such as marine bioresources remain largely untapped. Of these resources, marine sponges have undergone the most scrutiny for their biological activities, including antiinflammatory, antiviral, and anticancer properties. However, the biological mechanisms of the activities of these marine sponges are still unclear. We investigated the anticancer activity of marine sponges collected from Kosrae in Micronesia and examined their mechanisms of action using nonsmall cell lung cancer A549 cells as a model system. Of 20 specimens, the Haliclona sp. (KO1304-328) showed both dose- and time-dependent cytotoxicity. Further, methanol extracts of Haliclona sp. significantly inhibited cell proliferation and cell viability. A549 cells treated with Haliclona sp. demonstrated induced expression of c-Jun N-terminal kinase (JNK), p53, p21, caspase-8, and caspase-3. The percentage of apoptotic cells significantly increased in A549 cultures treated with Haliclona sp. These results indicate that Haliclona sp. induces apoptosis via the JNK-p53 pathway and caspase-8, suggesting that this marine sponge is a good resource for the development of drugs for treatment of nonsmall cell lung cancer.

No MeSH data available.


Related in: MedlinePlus