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1.
Int J Med Sci ; 16(8): 1107-1115, 2019.
Article in English | MEDLINE | ID: mdl-31523173

ABSTRACT

Astragalus membranaceus has been shown to possess anti-inflammation and antitumor properties. Several studies have indicated that extracts of Astragalus membranaceus (PG2) have growth inhibitory effects on tumor. However, the effect of PG2 on enhancing the chemotherapy, modulating tumor immune escape and their mechanism of action is unknown and need further investigation. Connexin (Cx) 43 is ubiquitous in cells and involved in facilitating the passage of chemotherapeutic drugs to bystander tumor cells. The indoleamine 2, 3-dioxygenase (IDO) depletes tryptophan, reduces the active T cell number and destroys immune surveillance. Herein, we provide evidence that the treatment of PG2 induced Cx43 expression, decreases IDO expression and enhances the distribution of chemotherapeutic drug. However, the effects of combination therapy (PG2 plus cisplatin) in animal models significantly retarded tumor growth and prolonged the survival. We believe that the information provided in this study may aid in the design of future therapy of PG2, suggest suitable combinations with chemotherapies.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Astragalus propinquus/chemistry , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Plant Extracts/pharmacology , Animals , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/pharmacology , Cell Death/drug effects , Cell Line, Tumor , Cisplatin/administration & dosage , Connexin 43/metabolism , Drug Screening Assays, Antitumor , Enzyme Inhibitors/pharmacology , Humans , Indoleamine-Pyrrole 2,3,-Dioxygenase/antagonists & inhibitors , Mice, Inbred C57BL , Plant Extracts/administration & dosage , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , T-Lymphocytes/pathology , Xenograft Model Antitumor Assays
2.
Int J Med Sci ; 16(4): 602-606, 2019.
Article in English | MEDLINE | ID: mdl-31171912

ABSTRACT

Hyperpigmentation is a type of pigmentary disorder induced by overexpression of melanin content activated severe esthetic problems as melasma, freckle, ephelides, lentigo and other forms on human skin. Several whitening agents have restricted use because of their side effects or stability such as kojic acid, ascorbic acid and hydroquinone can act as cytotoxic substance which associated to dermatitis and skin cancer. To find for the safe substance, this study aimed to find for the ability of several components in Sucrier banana peel (SBP) extracts to inhibit melanogenesis process through p38 signaling pathway in B16F10 mouse melanoma cells. Tyrosinase activity and the cellular melanin content were dose dependent manner decreasing after SBP treatment. Furthermore, SBP decreased the expression of melanogenesis relate protein as microphthalmia-associated transcription factor (MITF) and tyrosinase protein after 24 hours incubation with α-melanocyte stimulating hormones (MSH) stimulating. The findings demonstrated that SBP contained an effective agent for hyperpigmentation inhibitor through p38 signaling pathways without any effect to ERK pathway, and subsequent down-regulate MITF expression and tyrosinase enzyme family production.


Subject(s)
Hyperpigmentation/drug therapy , Melanins/biosynthesis , Melanoma, Experimental/drug therapy , Musa/chemistry , Animals , Cell Line, Tumor , Gene Expression Regulation, Neoplastic/drug effects , Humans , MAP Kinase Signaling System/drug effects , Melanins/antagonists & inhibitors , Melanoma, Experimental/genetics , Melanoma, Experimental/pathology , Mice , Microphthalmia-Associated Transcription Factor/genetics , Monophenol Monooxygenase/genetics , Plant Extracts/chemistry , Plant Extracts/pharmacology , alpha-MSH/pharmacology
3.
Int J Med Sci ; 16(5): 636-643, 2019.
Article in English | MEDLINE | ID: mdl-31217730

ABSTRACT

Chemotherapy is now in common use for the treatment of tumors; however, with tumor growth retardation comes the severe side effects that occur after a chemotherapy cycle. Eicosapentaenoic acids (EPA) used in combination with chemotherapy has an additive effects and provides a rationale for using EPA in tandem with chemotherapy. To improve the efficacy and safety of this combination therapy, a further understanding that EPA modulates with the tumor microenvironment is necessary. Connexin 43 (Cx43) is involved in enhancing chemosensitivity that was suppressed in a tumor microenvironment. We aim to investigate the role of EPA in chemosensitivity in murine melanoma by inducing Cx43 expression. The dose-dependent upregulation of Cx43 expression and gap junction intercellular communication were observed in B16F10 cells after EPA treatment. Furthermore, EPA significantly increased the expression levels of mitogen-activated protein kinases (MAPK) signaling pathways. The EPA-induced Cx43 expression was reduced after MAPK inhibitors. Knockdown Cx43 in B16F10 cells reduced the therapeutic effects of combination therapy (EPA plus 5-Fluorouracil). Our results demonstrate that the treatment of EPA is a tumor induced Cx43 gap junction communication and enhances the combination of EPA and chemotherapeutic effects.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Connexin 43/metabolism , Eicosapentaenoic Acid/pharmacology , Melanoma, Experimental/drug therapy , Skin Neoplasms/drug therapy , Animals , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cell Line, Tumor , Connexin 43/genetics , Dose-Response Relationship, Drug , Drug Synergism , Eicosapentaenoic Acid/therapeutic use , Fluorouracil/pharmacology , Fluorouracil/therapeutic use , Gene Expression Regulation, Neoplastic/drug effects , Gene Knockdown Techniques , Humans , MAP Kinase Signaling System/drug effects , Male , Melanoma, Experimental/pathology , Mice , Mice, Inbred C57BL , Mitogen-Activated Protein Kinases/antagonists & inhibitors , Protein Kinase Inhibitors/pharmacology , Skin Neoplasms/pathology , Tumor Microenvironment/drug effects , Up-Regulation/drug effects
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