The Leaf Extract of Mitrephora chulabhorniana Suppresses Migration and Invasion and Induces Human Cervical Cancer Cell Apoptosis through Caspase-Dependent Pathway.

Cervical cancer is rated to be the leading cause of cancer-related death in women worldwide. Since screening test and conventional treatments are less accessible for people in developing countries, an alternative use of medicinal plants exhibiting strong anticancer activities may be an affordable means to treat cervical cancer. Mitrephora chulabhorniana (MC) is the newly identified species; however, its biological functions including anticancer activities have been largely unexplored. Hence, in this study, we were interested in investigating anticancer effects of this plant on the human cervical cell line (HeLa). MC extract was profiled for phytochemicals by TLC. This plant was tested to contain alkaloids, flavonoids, and terpenes. HeLa cells were treated with MC extract to investigate the anticancer activities. Cytotoxicity and viability of cells treated with MC were determined by MTT assay and Trypan blue exclusion assay. Cell migration was tested by wound healing assay, and cell invasion was determined by Transwell assay. The level of caspase 7, caspase 9, and PARP was determined by western blot analysis. We found that the leaf extract of MC strongly reduced cancer cell survival rate. This finding was consistent with the discovery that the extract dramatically induced apoptosis of cervical cancer cells through the activation of caspase 7 and caspase 9 which consequently degraded PARP protein. Furthermore, MC extract at lower concentrations which were not cytotoxic to the cancer cells showed potent inhibitory activities against HeLa cervical cancer cell migration and invasion. Mitrephora chulabhorniana possesses its pharmacological properties in inhibiting cervical cancer cell migration/invasion and inducing apoptotic signaling. This accumulated information suggests that Mitrephora chulabhorniana may be a beneficial source of potential agents for cervical cancer treatment.

Essential Oil from Zingiber ottensii Induces Human Cervical Cancer Cell Apoptosis and Inhibits MAPK and PI3K/AKT Signaling Cascades.

Zingiber ottensii (ZO) is a local plant in Thailand and has been used as a Thai traditional therapy for many conditions. ZO has been reported to exhibit many pharmacological effects, including anti-cancer activity. Nevertheless, its anti-cancer effects explored at the signaling level have not been elucidated in cervical cancer, which is one of the leading causes of fatality in females. We discovered that the essential oil of ZO significantly increased the apoptosis of human cervical cancer cells (HeLa) after 24 h of treatment in a concentration-dependent manner. Our data also clearly demonstrated that ZO essential oil reduced IL-6 levels in the culture supernatants of the cancer cells. Moreover, Western blot analysis clearly verified that cells were induced to undergo apoptotic death via caspase activation upon treatment with ZO essential oil. Interestingly, immunofluorescence studies and Western blot analyses showed that ZO essential oil suppressed epidermal growth factor (EGF)-induced pAkt and pERK1/2 signaling pathway activation. Together, our study demonstrates that ZO essential oil can reduce the proliferation and survival signaling of HeLa cervical cancer cells. Our study provides convincing data that ZO essential oil suppresses the growth and survival of cervical cancer cells, and it may be a potential choice for developing an anti-cancer agent for treating certain cervical cancers.

Kaempferia parviflora extract inhibits TNF-α-induced release of MCP-1 in ovarian cancer cells through the suppression of NF-κB signaling.

Ovarian clear cell carcinoma (OCCC) is an uncommon subtype of epithelial cell ovarian cancers (EOCs) that has poor response to conventional platinum-based therapy. Therefore, finding new potential therapeutic agents is required. Since inflammatory cytokine, tumor necrosis factor alpha (TNF-α), is strongly expressed in EOCs and associated with the level of tumor grade, disruption of this inflammation pathway may provide another potential target for OCCC treatment. We previously reported that Kaempferia parviflora (KP) extract decreased cell proliferation and induced apoptosis. However, the effects of KP on OCCC, especially the aspects related to inflammatory cytokines, have not been elucidated. Our current study demonstrated the effects of KP extract on cytokine production in TNF-α-induced OCCC TOV-21G cell line. This study showed that KP extract inhibited interleukin 6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) production at both transcription and translation levels via the suppression of nuclear factor-kappa B (NF-κB) signal transduction. In contrast, KP extract increased the expression of inhibitor kappa B (IκB) protein which may delay NF-κB translocation into the nucleus upon TNF-α activation. Moreover, the suppression of cytokines released from KP treated-TOV-21G reduced the migration of monocyte cell (THP-1). KP extract also exhibited the inhibition of IL-6 and MCP-1 production from THP-1 activated by lipopolysaccharides (LPS). Cells treated with KP extract exhibited a decrease in extracellular signal-regulated kinases (ERK1/2) and protein kinase B (AKT) phosphorylation and induced myeloid leukemia cell differentiation protein Mcl-1 (MCL-1) expression. Suppression of inflammatory cytokine and chemokine production and inhibition of tumor-associated macrophage (TAM) migration support the possibility of using KP for OCCC treatment.

Curcuma amarissima Extract Activates Growth and Survival Signal Transduction Networks to Stimulate Proliferation of Human Keratinocyte.

Many medicinal plants have been used to treat wounds. Here, we revealed the potential wound healing effects of Curcuma amarissima (CA). Our cell viability assay showed that CA extract increased the viability of HaCaT cells that were cultured in the absence of serum. This increase in cell viability was proved to be associated with the pharmacological activities of CA extract in inducing cell proliferation. To further define possible molecular mechanisms of action, we performed Western blot analysis and immunofluorescence study, and our data demonstrated that CA extract rapidly induced ERK1/2 and Akt activation. Consistently, CA extract accelerated cell migration, resulting in rapid healing of wounded human keratinocyte monolayer. Specifically, the CA-induced increase of cell monolayer wound healing was blocked by the MEK inhibitor (U0126) or the PI3K inhibitor (LY294002). Moreover, CA extract induced the expression of Mcl-1, which is an anti-apoptotic protein, supporting that CA extract enhances human keratinocyte survival. Taken together, our study provided convincing evidence that Curcuma amarissima can promote proliferation and survival of human keratinocyte through stimulating the MAPK and PI3K/Akt signaling cascades. These promising data emphasize the possibility to develop this plant as a wound healing agent for the potential application in regenerative medicine.

Boesenbergia rotunda extract accelerates human keratinocyte proliferation through activating ERK1/2 and PI3K/Akt kinases.

Boesenbergia rotunda (BR) has long been used as tradition medicine. For its pharmacological effects on wound healing, previous studies in an animal model provided convincing results that the ethanolic extract from the rhizome of this plant can stimulate wound healing. However, the mechanism about how this plant promotes wound healing at the molecular level has not been elucidated. As a step towards the development of wound healing agents, our current study utilized a human keratinocyte cell line (HaCaT) as an in vitro model to define the potential molecular mechanisms of BR extract in enhancing wound-healing. Our HPLC results showed that BR extract contained kaempferol as one of its potential compounds. The extract strongly promoted wound healing of HaCaT cell monolayer. This effect was eventually defined to be regulated through the ability of BR extract to induce cell proliferation. At the signaling level, we discovered that BR extract rapidly activated ERK1/2 and Akt phosphorylation upon the addition of the extract. Additionally, our experiments where specific inhibitors of MEK (U0126) and PI3K (LY294002) were utilized verified that BR enhanced cell proliferation and wound healing through stimulating the MAPK and PI3K/Akt signal transduction pathways. Moreover, direct inhibition of keratinocyte DNA synthesis by mitomycin C (MMC) could completely block the proliferative effects of BR extract. Nevertheless, data from Transwell migration assay revealed that BR extract did not promote keratinocyte migration. Altogether, we provided more evidence that BR possesses its wound healing-promoting action through the activation of proliferation and survival pathways, and our study suggests that BR is an interesting candidate to be developed as a wound healing-promoting agent.