Inhibitory effect of capsaicin on B16-F10 melanoma cell migration via the phosphatidylinositol 3-kinase/Akt/Rac1 signal pathway

Shin, Dong Hoon; Kim, Ok Hee; Jun, Hey Jung; Kang, Myounggon

doi:10.3858/emm.2008.40.5.486

Cited by 88 publications

(67 citation statements)

References 28 publications

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“…Recently, many natural extracts have been demonstrated to inhibit migration in various cancer cells via PI3K/AKT, a downstream pathway of FAK [34][35][36][37]. The activity of RhoGTPase proteins is also regulated by the function of activated Akt (pAkt) [38][39][40].…”

Section: Discussionmentioning

confidence: 99%

A bibenzyl from Dendrobium ellipsophyllum inhibits migration in lung cancer cells

Chaotham

Chanvorachote

2015

J Nat Med

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Metastatic cancer cells have been shown to have aggressive behaviors accounting for the high incidence of chemotherapeutic failure and mortality. Because migration and invasion are crucial behaviors for cancer cell dissemination, promising compounds exhibiting potential antimigration effects are of interest for metastasis-based therapeutic approaches. This study aimed to evaluate the activity of a bibenzyl, 4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl (TDB), isolated from Dendrobium ellipsophyllum Tang and Wang, in the suppression of migration in human lung cancer cells. TDB at nontoxic concentrations (1 and 5 µM) significantly inhibited the motility of lung cancer cells in scratch-wound assay. Chemotaxis-induced migration and invasion assays also revealed that the cell motility dramatically diminished in the cells treated with 1-5 µM TDB. Western blot analysis provided the underlying molecular mechanism, showing that TDB reduced such cell migration and invasion by decreasing migration-regulating proteins, including integrins αv, α4, β1, β3 and β5, as well as downstream signaling proteins, such as activated focal adhesion kinase (pFAK), activated Ras-related C3 botulinum toxin substrate 1 (Rac1-GTP) and cell division control protein 42 (Cdc42). As the presence of cellular protrusion, called filopodia, has been indicated as a hallmark of migrating cells, we showed that the reduction of the mentioned proteins correlated well with the disappearance of filopodia. In summary, this study demonstrates the promising activity of TDB and its mechanism in the inhibition of lung cancer cell migration, which might be useful for encouraging the development of this compound for antimetastatic approaches.

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Section: Discussionmentioning

confidence: 99%

A bibenzyl from Dendrobium ellipsophyllum inhibits migration in lung cancer cells

Chaotham

Chanvorachote

2015

J Nat Med

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“…Capsaicin is the principal pungent ingredient present in red peppers, which are among the most frequently consumed spices worldwide (14,15). Capsaicin has been revealed to possess inhibitory effects in various cancer cells (18)(19)(20)22,24). However, the precise molecular mechanisms have not been well elucidated in pancreatic cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, capsaicin treatment has significantly suppressed the growth of tumors in athymic nude mice transplanted with cancer cells (22,23). Capsaicin was also revealed to inhibit the PI3K/Akt pathway in B16-F10 melanoma cells (24). However, data regarding the properties of capsaicin in pancreatic cancer cells remain limited and the mechanisms of apoptosis have not yet been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Involvement of the phosphoinositide 3-kinase/Akt pathway in apoptosis induced by capsaicin in the human pancreatic cancer cell line PANC-1

et al. 2012

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Abstract. Capsaicin, one of the major pungent ingredients found in red peppers, has been recently demonstrated to induce apoptosis in various malignant cell lines through an unclear mechanism. In this study, the effect of capsaicin on proliferation and apoptosis in the human pancreatic cancer cell line PANC-1 and its possible mechanism(s) of action were investigated. The results of a Cell Counting Kit-8 (CCK-8) assay revealed that capsaicin significantly decreased the viability of PANC-1 cells in a dose-dependent manner. Capsaicin induced G0/G1 phase cell cycle arrest and apoptosis in PANC-1 cells as demonstrated by a flow cytometric assessment. Caspase-3 expression at both the protein and mRNA level was promoted following capsaicin treatment. Furthermore, we revealed that phospho-PI3 Kinase p85 (Tyr458) and phospho-Akt (Ser473) in PANC-1 cells were downregulated in response to capsaicin. Moreover, capsaicin gavage significantly inhibited the growth of pancreatic cancer PANC-1 cell xenografts in athymic nude mice. An increased number of TUNEL-positive cells and cleaved caspase-3 were observed in capsaicin-treated mice. In vivo, capsaicin downregulated the expression of phospho-PI3 Kinase p85 (Tyr458) and phospho-Akt (Ser473).In conclusion, we have demonstrated that capsaicin is an inhibitor of growth of PANC-1 cells, and downregulation of the phosphoinositide 3-kinase/Akt pathway may be involved in capsaicin-induced apoptosis in vitro and in vivo.

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“…To confirm the migration capacity of the MA-treated cells, the scratch motility assay was carried out (Shin et al, 2008). B16F10 melanoma cells (1x10 5 cells/well) were seeded into a 24 well culture plate and were allowed to grow overnight to reach confluency.…”

Section: Scratch Motility Assaymentioning

confidence: 99%

Anti-metastatic Effects on B16F10 Melanoma Cells of Extracts and Two Prenylated Xanthones Isolated from Maclura amboinensis Bl. Roots

Siripong¹,

Rassamee²,

Piyaviriyakul³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Inhibitory effects of Maclura amboinenesis Bl, one plant used traditionally for the treatment of cancers, on metastatic potential of highly metastatic B16F10 melanoma cells were investigated in vitro. Cell proliferation was assessed using the MTT colorimetric assay. Details of metastatic capabilities including invasion, migration and adhesion of B16F10 melanoma cells were examined by Boyden Chamber invasion and migration, scratch motility and cell attachment assays, respectively. The results demonstrated that n-hexane and chloroform extracts exhibited potent anti-proliferative effects (p<0.01), whereas the methanol and aqueous extracts had less pronounced effects after 24 h exposure. Bioactivity-guided chromatographic fractionation of both active n-hexane and chloroform extracts led to the isolation of two main prenylated xanthones and characterization as macluraxanthone and gerontoxanthone-I, respectively, their structures being identified by comparison with the spectral data. Interestingly, both exhibited potent effective effects. At non-toxic effective doses, n-hexane and chloroform extracts (10 and 30 µg/ml) as well as macluraxanthone and gerontoxanthone-I (3 and 10 µM) significantly inhibited B16F10 cell invasion, to a greater extent than 10 µM doxorubicin, while reducing migration of cancer cells without cellular cytotoxicity. Moreover, exposure of B16F10 melanoma cells to high concentrations of chloroform (30 µg/ml) and geratoxanthone-I (20 µM) for 24 h resulted in delayed adhesion and retarded colonization. As insights into mechanisms of action, typical morphological changes of apoptotic cells e.g. membrane blebbing, chromatin condensation, nuclear fragmentation, apoptotic bodies and loss of adhesion as well as cell cycle arrest in the G1 phase with increase of sub-G1 cell proportions, detected by Hoechst 33342 staining and flow cytometry were observed, suggesting DNA damage and subsequent apoptotic cell death. Taken together, our findings indicate for the first time that active n-hexane and chloroform extracts as well as macluraxanthone and gerontoxanthone-I isolated from Maclura amboinensis Bl. roots affect multistep of cancer metastasis processes including proliferation, adhesion, invasion and migration, possibly through induction of apoptosis of highly metastatic B16F10 melanoma cells. Based on these data, M. amboinensis Bl. represents a potential candidate novel chemopreventive and/or chemotherapeutic agent. Additionally, they also support its ethno-medicinal usage for cancer prevention and/or chemotherapy.

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Inhibitory effect of capsaicin on B16-F10 melanoma cell migration via the phosphatidylinositol 3-kinase/Akt/Rac1 signal pathway

Cited by 88 publications

References 28 publications

A bibenzyl from Dendrobium ellipsophyllum inhibits migration in lung cancer cells

A bibenzyl from Dendrobium ellipsophyllum inhibits migration in lung cancer cells

Involvement of the phosphoinositide 3-kinase/Akt pathway in apoptosis induced by capsaicin in the human pancreatic cancer cell line PANC-1

Anti-metastatic Effects on B16F10 Melanoma Cells of Extracts and Two Prenylated Xanthones Isolated from Maclura amboinensis Bl. Roots

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