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1.
Photodynamic therapy inhibits melanogenesis through paracrine effects by keratinocytes and fibroblasts
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Sue Kyung Kim Seung‐Jae Oh Se‐Yeon Park Woo‐Jung Kim You‐Sun Kim You Chan Kim 《Pigment cell & melanoma research》2018,31(2):277-286
Photodynamic therapy (PDT) is a treatment option for skin cancer and premalignant skin diseases and exhibits rejuvenation effects, including reducing fine wrinkles and whitening, on aged skin. In this study, we investigated the mechanism underlying the whitening effects of PDT on melanocytes (MCs) in vitro and in vivo. Exposure of MCs to PDT in vitro reduced their melanin content and tyrosinase activity without, however, affecting cell survival. Interestingly, melanogenesis was also inhibited by exposing MCs to conditioned media of PDT‐treated keratinocytes or dermal fibroblasts. This paracrine effect was likely due to a decreased release of melanocyte‐stimulating cytokines such as Kit ligand and hepatocyte growth factor from these cells. Furthermore, we observed that PDT reduced mottled hyperpigmentation of photoaged patient skin in vivo, highlighting the clinical importance of skin whitening by PDT. 相似文献
2.
V. Vaz Serra A. Zamarrón M.A.F. Faustino M.C. Iglesias-de la Cruz A. Blázquez J.M.M. Rodrigues M.G.P.M.S. Neves J.A.S. Cavaleiro A. Juarranz F. Sanz-Rodríguez 《Bioorganic & medicinal chemistry》2010,18(16):6170-6178
The efficacy of new porphyrin amino acid conjugates as photosensitizers for photodynamic therapy (PDT) were assayed in vitro on tumoral (HeLa) and on non tumoral (HaCaT) human cell lines. The conjugates stable in liposomes are able to penetrate efficiently in the cytoplasm of cultured cancer and normal cells. No dark cytotoxicity is observed at the same concentration used for PDT cell treatment and during long incubation time (24 h). The cell survival after the PDT treatment with visible light is dependent upon light exposure level and compound concentration. The tested compounds show higher photocytotoxicity in tumoral HeLa cells than in no tumoral HaCaT cells. The results suggest that these amino acid porphyrin conjugates are potential photosensitizers for PDT. 相似文献
3.
多腺苷二磷酸核糖聚合酶(poly(ADP-ribose) polymerase, PARP)抑制剂是一类靶向 DNA 修复缺陷癌细胞的新型药物。早期研究表明 PARP 抑制剂取得了令人满意的结果,然而药物治疗后出现的耐药机制尚未完全揭露。因此,有必要寻找更多的靶向药物与PARP 抑制剂联用,以达到杀伤肿瘤细胞的目的。本文基于379种小分子化合物和PARP抑制剂尼拉帕尼(Niraparib)的联合用药筛选,通过细胞增殖实验、克隆存活实验和免疫荧光染色等方法筛选潜在的具有协同PARP抑制剂杀伤卵巢癌细胞的药物。结果表明,其中有8种小分子化合物具有较好的联合用药效果,包括2种已经报道的与PARP抑制剂具有联用效果的小分子化合物STF-118804和Disulfiram。我们从中选取原肌球蛋白受体激酶 A (tropomyosin receptor kinase A,TrKA)的抑制剂GW441756,进行了多种肿瘤细胞的验证以及初步机制的探究。Niraparib和TrKA抑制剂的联合用药显著增加肿瘤细胞对PARP抑制剂的敏感性(P<0.05)。从机制上分析,联合用药组细胞内γH2AX foci的数目显著增加(P<0.05),说明TrKA抑制剂阻碍损伤后细胞的DNA损伤修复能力;同时,联合用药显著降低细胞内同源重组修复(homologous recombination repair,HRR)标志物RAD51 foci(P<0.05)的形成,说明TrKA抑制剂可能通过抑制细胞的HRR效率阻碍细胞的DNA损伤修复。本研究的结果提示,TrKA抑制剂可以作为一种与PARP抑制剂联用杀伤卵巢癌细胞的潜在药物。 相似文献
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5.
Up-regulation of transient receptor potential canonical 1 (TRPC1) following sarco(endo)plasmic reticulum Ca2+ ATPase 2 gene silencing promotes cell survival: a potential role for TRPC1 in Darier's disease
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Pani B Cornatzer E Cornatzer W Shin DM Pittelkow MR Hovnanian A Ambudkar IS Singh BB 《Molecular biology of the cell》2006,17(10):4446-4458
The mechanism(s) involved in regulation of store operated calcium entry in Darier's disease (DD) is not known. We investigated the distribution and function of transient receptor potential canonical (TRPC) in epidermal skin cells. DD patients demonstrated up-regulation of TRPC1, but not TRPC3, in the squamous layers. Ca2+ influx was significantly higher in keratinocytes obtained from DD patients and showed enhanced proliferation compared with normal keratinocytes. Similar up-regulation of TRPC1 was also detected in epidermal layers of SERCA2+/- mice. HaCaT cells expressed TRPC1 in the plasma membrane. Expression of sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA)2 small interfering RNA (siRNA) in HaCaT cells increased TRPC1 levels and thapsigargin-stimulated Ca2+ influx, which was blocked by store-operated calcium entry inhibitors. Thapsigargin-stimulated intracellular Ca2+ release was decreased in DD cells. DD keratinocytes exhibited increased cell survival upon thapsigargin treatment. Alternatively, overexpression of TRPC1 or SERCA2-siRNA in HaCaT cells demonstrated resistance to thapsigargin-induced apoptosis. These effects were dependent on external Ca2+ and activation of nuclear factor-kappaB. Isotretinoin reduced Ca2+ entry in HaCaT cells and decreased survival of HaCaT and DD keratinocytes. These findings put forward a novel consequence of compromised SERCA2 function in DD wherein up-regulation of TRPC1 augments cell proliferation and restrict apoptosis. We suggest that the anti-apoptotic effect of TRPC1 could potentially contribute to abnormal keratosis in DD. 相似文献
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Up-regulation of cell adhesion molecules and proinflammatory cytokines contributes to enhanced monocyte adhesiveness and infiltration into the skin, during the pathogenesis of various inflammatory skin diseases, including atopic dermatitis. In this study, we examined the anti-inflammatory effects of butein, a tetrahydroxychalcone, and its action mechanisms using TNF-α-stimulated keratinocytes. Butein significantly inhibited TNF-α-induced ICAM-I expression and monocyte adhesion in human keratinocyte cell line HaCaT. Butein also decreased TNF-α-induced pro-inflammatory mediators, such as IL-6, IP-10 and MCP-1, in HaCaT cells. Butein decreased TNF-α-induced ROS generation in a dose-dependent manner in HaCaT cells. In addition, treatment of HaCaT cells with butein suppressed TNF-α-induced MAPK activation. Furthermore, butein suppressed TNF-α-induced NF-kappaB activation. Overall, our results indicate that butein has immunomodulatory activities by inhibiting expression of proinflammatory mediators in keratinocytes. Therefore, butein may be used as a therapeutic agent for the treatment of inflammatory skin diseases. [BMB Reports 2015; 48(9): 495-500] 相似文献
8.
UVB radiation damages keratinocytes, potentially inducing chronic skin damage, cutaneous malignancy, and suppression of the immune system. Naturally occurring agents have been considered for prevention and treatment of various kinds of cancer, including skin cancer. Inositol hexaphosphate (IP6), an antioxidant, is a naturally occurring polyphosphorylated carbohydrate that has shown a strong anticancer activity in several experimental models. We assessed the protective effects of IP6 against UVB irradiationinduced injury and photocarcinogenesis by using HaCaT cells (human immortalized keratinocytes) and SKH1 hairless mice. We found that IP6 counteracts the harmful effects of UVB irradiation and increases the viability and survival of UVB-exposed cells. Treatment with IP6 after UVB irradiation (30 mJ/cm(2)) arrested cells in the G(1) and G(2) M phases while decreasing the S phase of the cell cycle. Treatment with IP6 also decreased UVB-induced apoptosis and caspase 3 activation. Topical application of IP6 followed by exposure to UVB irradiation in SKH1 hairless mice decreased tumor incidence and multiplicity as compared with control mice. Our results suggest that IP6 protects HaCaT cells from UVB-induced apoptosis and mice from UVB-induced tumors. 相似文献
9.
Li R Bounds DJ Granville D Ip SH Jiang H Margaron P Hunt DW 《Apoptosis : an international journal on programmed cell death》2003,8(3):269-275
QLT0074 is a newly introduced, porphyrin-derivative for use in photodynamic therapy (PDT). In the current study, the intracellular distribution of QLT0074 and the mode of cell death induced by photosensitization with this compound in vitro were assessed for transformed human HaCaT keratinocytes. Fluorescence microscopy studies indicated a distribution of the drug to the cytoplasm, nuclear membrane and mitochondria of these cells. In the absence of light, QLT0074 produced no evidence of apoptosis-related biochemical changes or affected cell viability. When combined with blue light exposure, cytotoxicity was exerted in a QLT0074- and light-dose-related manner. Appearance of the mitochondrial protein cytochrome c in the cytosolic fraction and expression of the apoptosis-associated mitochondrial 7A6 antigen were demonstrable following photosensitization at nano-molar levels of QLT0074. Evidence of processing of the apoptosis-effector molecules caspase-3, -6, -7, -8 and -9 as well as cleavage of the caspase-3 substrate poly (ADP-ribose) polymerase (PARP) were demonstrable subsequent to cytochrome c release after PDT. Treatment with the anti-oxidant pyrrolidine dithiocarbamate (PDTC) inhibited cytochrome c release, caspase-3 activation and PARP cleavage associated with PDT thereby supporting the contention that QLT0074 induces apoptosis through the generation of reactive oxygen species upon light activation. QLT0074 is a potent photosensitizer with the capacity to directly initiate apoptosis by acting upon mitochondria. 相似文献
10.
《Bioorganic & medicinal chemistry》2019,27(15):3279-3284
Photodynamic therapy (PDT) is a treatment method using light and photosensitizers (PSs), which is categorized as a non-invasive surgery treatment for cancers. When the tumor is exposed to a specific light, the PSs become active and generate reactive oxygen species (ROS), mainly singlet oxygen which kills nearby cancer cells. PDT is becoming more widely recognized as a valuable treatment option for localized cancers and pre-cancers of skin as it has no long-term effects on the patient. But, due to the limited penetration rate of light into the skin and other organs, PDT can’t be used to treat large cancer cells or cancer cells that have grown deeply into the skin or other organs. Hence, in this study, our focus centers on synthesizing glucose-conjugated phthalocyanine (Pc) compatible with near-infrared (NIR) irradiation as second-generation photosensitizer, so that PDT can be used in a wider range to treat cancers without obstacles. 相似文献
11.
Serini S Donato V Piccioni E Trombino S Monego G Toesca A Innocenti I Missori M De Spirito M Celleno L Fasano E Ranelletti FO Calviello G 《The Journal of nutritional biochemistry》2011,22(9):874-885
The dramatic increase in the incidence of nonmelanoma skin cancer over the last decades has been related to the augmented exposure to ultraviolet (UV) radiation (UVR). It is known that apoptosis is induced as a protective mechanism after the acute irradiation of keratinocytes, whereas apoptotic resistance and carcinogenesis may follow the chronic exposure to UVR. We found that not all the human keratinocytes lines studied underwent apoptosis following acute exposure to UVR (10-60 mJ/cm2). Whereas UVR induced apoptosis in the HaCaT cells, NCTC 2544 and nr-HaCaT cells showed apoptosis resistance. The cytokeratin pattern of the apoptosis-resistant cells indicated that they possessed a degree of differentiation lower than that of HaCaT cells. They also showed an enhanced expression of cyclooxygenase-2 (COX-2), an early marker of carcinogenesis in various tissues, including skin. n-3 polyunsaturated fatty acids have drawn increasing interest as nutritional factors with the potential to reduce UVR carcinogenesis, and since they are apoptosis inducers and COX-2 inhibitors in cancer cells, we investigated the ability of n-3 polyunsaturated fatty acids to influence the resistance to UVR-induced apoptosis in keratinocytes. We observed that docosahexaenoic acid (DHA) reverted the resistance of nr-HaCaT cells to UVR-induced apoptosis, increasing the Bax/Bcl-2 ratio and caspase-3 activity, and reduced COX-2 levels by inhibiting the expression of the human antigen R (HuR), a known COX-2 mRNA stabilizer in keratinocytes. The transfection of nr-HaCaT cells with HuR siRNA mimicked the proapoptotic effect of DHA. Overall, our findings further support the role of DHA as a suitable anticarcinogenic factor against nonmelanoma skin cancers. 相似文献
12.
《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2023,1870(7):119549
Microenvironment of the melanoma consists of cellular elements like fibroblasts, adipocytes, and keratinocytes as well as extracellular matrix and physicochemical conditions. In our previous research, we have established that melanoma influences strongly above mentioned cells present in the tumor niche and recruits them to support cancer progression. In this work, we evaluated the impact of cancer-associated cells, namely fibroblasts (CAFs), adipocytes (CAAs), and keratinocytes (CAKs) on melanoma proliferation, signaling pathways activation, metabolism as well as the effectiveness of used anti-cancer therapy. Obtained results indicated elevated phosphorylation of STAT3, upregulated GLUT1 and GLUT3 as well as downregulated of MCT-1 expression level in melanoma cells under the influence of all examined cells present in the tumor niche. The proliferation of melanoma cells was increased after co-culture with CAFs and CAKs, while epithelial-mesenchymal transition markers' expression level was raised in the presence of CAFs and CAAs. The level of perilipin 2 and lipid content was elevated in melanoma cells under the influence of CAAs. Moreover, increased expression of CYP1A1, gene encoding drug metabolizing protein, in melanoma cells co-cultured with CAFs and CAKs prompted us to verify the effectiveness of the previously proposed by us anti-melanoma therapy based on combination of EGFR and MET inhibitors. Obtained results indicate that the designed therapy is still efficient, even if the fibroblasts, adipocytes, and keratinocytes, are present in the melanoma vicinity. 相似文献
13.
Sae-Bom Kwon Min-Je Kim Jin Mo Yang Hee-Pom Lee Jin Tae Hong Heon-Sang Jeong Eun Suk Kim Do-Young Yoon 《PloS one》2016,11(3)
The focus of this study is the anti-cancer effects of Cudrania tricuspidata stem (CTS) extract on cervical cancer cells. The effect of CTS on cell viability was investigated in HPV-positive cervical cancer cells and HaCaT human normal keratinocytes. CTS showed significant dose-dependent cytotoxic effects in cervical cancer cells. However, there was no cytotoxic effect of CTS on HaCaT keratinocytes at concentrations of 0.125–0.5 mg/mL. Based on this cytotoxic effect, we demonstrated that CTS induced apoptosis by down-regulating the E6 and E7 viral oncogenes. Apoptosis was detected by DAPI staining, annexin V-FITC/PI staining, cell cycle analysis, western blotting, RT-PCR, and JC-1 staining in SiHa cervical cancer cells. The mRNA expression levels of extrinsic pathway molecules such as Fas, death receptor 5 (DR5), and TNF-related apoptosis-inducing ligand (TRAIL) were increased by CTS. Furthermore, CTS treatment activated caspase-3/caspase-8 and cleavage of poly (ADP-ribose) polymerase (PARP). However, the mitochondrial membrane potential and expression levels of intrinsic pathway molecules such as Bcl-2, Bcl-xL, Bax, and cytochrome C were not modulated by CTS. Taken together, these results indicate that CTS induced apoptosis by activating the extrinsic pathway, but not the intrinsic pathway, in SiHa cervical cancer cells. These results suggest that CTS can be used as a modulating agent in cervical cancer. 相似文献
14.
Nicoletta Vitale Annamaria Kisslinger Simona Paladino Claudio Procaccini Giuseppe Matarese Giovanna Maria Pierantoni Francesco Paolo Mancini Donatella Tramontano 《PloS one》2013,8(11)
UVB radiation causes about 90% of non-melanoma skin cancers by damaging DNA either directly or indirectly by increasing levels of reactive oxygen species (ROS). Skin, chronically exposed to both endogenous and environmental pro-oxidant agents, contains a well-organised system of chemical and enzymatic antioxidants. However, increased or prolonged free radical action can overwhelm ROS defence mechanisms, contributing to the development of cutaneous diseases. Thus, new strategies for skin protection comprise the use of food antioxidants to counteract oxidative stress. Resveratrol, a phytoalexin from grape, has gained a great interest for its ability to influence several biological mechanisms like redox balance, cell proliferation, signal transduction pathways, immune and inflammatory response. Therefore, the potential of resveratrol to modify skin cell response to UVB exposure could turn out to be a useful option to protect skin from sunlight-induced degenerative diseases. To investigate into this matter, HaCaT cells, a largely used model for human skin keratinocytes, were treated with 25 or 100 µM resveratrol for 2 and 24 hours prior to UVB irradiation (10 to 100 mJ/cm2). Cell viability and molecular markers of proliferation, oxidative stress, apoptosis, and autophagy were analyzed. In HaCaT cells resveratrol pretreatment: reduces UVB-induced ROS formation, enhances the detrimental effect of UVB on HaCaT cell vitality, increases UVB-induced caspase 8, PARP cleavage, and induces autophagy. These findings suggest that resveratrol could exert photochemopreventive effects by enhancing UVB-induced apoptosis and by inducing autophagy, thus reducing the odds that damaged cells could escape programmed cell death and initiate malignant transformation. 相似文献
15.
Sodium butyrate induced keratinocyte apoptosis 总被引:1,自引:0,他引:1
Daehn IS Varelias A Rayner TE 《Apoptosis : an international journal on programmed cell death》2006,11(8):1379-1390
Apoptosis of keratinocytes is a key mechanism required for epidermal homeostasis and the renewal of damaged cells. Its dysregulation
has been implicated in many skin diseases including cancer and hyperproliferative disorders. In the present study, the effect
of sodium butyrate, a histone deacetylase inhibitor, on keratinocyte apoptosis was investigated using the HaCaT human keratinocyte
cell line. Sodium butyrate induced morphological changes associated with apoptosis and nuclear fragmentation of HaCaTs. Annexin
V staining demonstrated that sodium butyrate induced apoptosis in a dose and time-dependent manner with 50% of HaCaTs apoptotic
after exposure to 0.8 mg/ml sodium butyrate for 24 h. Apoptosis was associated with upregulation of cell surface expression
of the death receptor Fas and activation of the extrinsic caspase pathway, with induction of caspase 8 activity peaking after
8 h. Caspase 3 activity peaked after 24 h and was associated with cleavage of the caspase 3 substrate, poly (ADP-ribose) polymerase
(PARP). The intrinsic caspase pathway was not activated as caspase 9 activity was not detected, and there was no change in
the expression of terminal differentiation markers keratin 10 and involucrin following sodium butyrate treatment. Together
these results indicate that sodium butyrate is a potent inducer of Fas associated apoptosis via caspase activation in HaCaT
keratinocytes, an effect that is independent of the induction of terminal differentiation. 相似文献
16.
Expression of VEGFR-2 on HaCaT cells is regulated by VEGF and plays an active role in mediating VEGF induced effects 总被引:4,自引:0,他引:4
Yang XH Man XY Cai SQ Yao YG Bu ZY Zheng M 《Biochemical and biophysical research communications》2006,349(1):31-38
Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 play important roles in mitogenesis and chemotaxis of endothelial cells. In normal human skin, VEGF is expressed and secreted by epidermal keratinocytes. Emerging data suggest that keratinocyte-derived VEGF targets other cell types besides the dermal endothelial cells. We have recently showed that keratinocytes from human normal skin expressed all five known VEGF receptors and co-receptors (neuropilin 1 and 2). To define the functional significance of VEGFR-2 in epidermis, we examined its role in a keratinocyte cell line, HaCaT cells, in response to VEGF treatment. Expression of VEGFR-2 on HaCaT cells was confirmed at both RNA and protein levels and was regulated by VEGF165 treatment. Treatment of HaCaT cells with VEGF165 induced tyrosine-autophosphorylation of VEGFR-2 and phosphorylation of PLC-gamma and p44/42 MAPK in a time-dependent manner. Preincubation with a neutralizing antibody for VEGFR-2 (MAB3571) completely abrogated these phosphorylation effects. Furthermore, VEGF165 stimulated proliferation and migration of HaCaT cells, and this effect was significantly blocked by a pretreatment with MAB3571. Neutralizing VEGFR-2 in HaCaT cells increased cell adhesion during culture. Our results suggest that VEGFR-2 expressed on HaCaT cells plays a crucial role in VEGF-mediated regulation of cell activity. 相似文献
17.
Cathepsin B is essential for regeneration of scratch-wounded normal human epidermal keratinocytes 总被引:10,自引:0,他引:10
Büth H Luigi Buttigieg P Ostafe R Rehders M Dannenmann SR Schaschke N Stark HJ Boukamp P Brix K 《European journal of cell biology》2007,86(11-12):747-761
Migration, proliferation and differentiation of keratinocytes are important processes during tissue regeneration and wound healing of the skin. Here, we focussed on proteases that contribute to extracellular matrix (ECM) remodeling as a prerequisite of keratinocyte migration. In particular, we assessed the significance of the mammalian cysteine peptidase cathepsin B for human keratinocytes during regeneration from scratch wounding. We describe the construction of a scratch apparatus that allows applying scratches of defined length, width and depth to cultured cells in a reproducible fashion. The rationale for our approach derived from our previous work where we have shown that HaCaT keratinocytes secrete cathepsin B into the extracellular space during spontaneous and induced migration. Here, we observed rapid removal of type IV collagen from underneath lamellipodial extensions of keratinocytes at the advancing fronts of regenerating monolayers, indicating that proteolytic ECM remodeling starts upon initiation of keratinocyte migration. Furthermore, we verified our previous results with HaCaT cells by using normal human epidermal keratinocytes (NHEK) and show that non-cell-permeant cathepsin B-specific inhibitors delayed full regeneration of the monolayers from scratch wounding in both cell systems, HaCaT and NHEK. Application of a single dose of cathepsin B inhibitor directly after scratch wounding of keratinocytes demonstrated that cathepsin B is essential during initial stages of wound healing, while its contribution to the subsequent processes of proliferation and differentiation of keratinocytes was of less significance. This notion was supported by our observation that the cathepsin B inhibitors used in this study did not affect proliferation rates of keratinocytes of regenerating cultures. Thus, we conclude that cathepsin B is indeed involved in ECM remodeling after its secretion from migrating keratinocytes. Cathepsin B might directly cleave ECM constituents or it may initiate proteolytic cascades that involve other proteases with the ability to degrade ECM components. Because cathepsin B is important for enabling migration of both, HaCaT cells and NHEK, our results support the notion that HaCaT keratinocytes represent an excellent cell culture model for analysis of human epidermal skin keratinocyte migration. 相似文献
18.
Kontargiris E Kolettas E Vadalouca A Trougakos IP Gonos ES Kalfakakou V 《Cell research》2004,14(5):415-422
Local anesthetics inhibit cell proliferation and induce apoptosis in various cell types. Ropivacaine, a unique, novel tertiary amine-type anesthetic, was shown to inhibit the proliferation of several cell types including keratinocytes. We found that Ropivacaine could inhibit the proliferation and induce apoptosis in an immortalized human keratinocyte line,HaCaT, in a dose- and time-dependent manner and with the deprivation of serum. The dose-dependent induction of apoptosis by ropivacaine was demonstrated by DNA fragmentation analysis and the proteolytic cleavage of a caspase-3 substrate—poly (ADP-ribose) polymerase (PARP). In addition, ropivacaine downregulated the expression of clusterin/ apoliporotein J, a protein with anti-apoptotic properties, in a dose-dependent manner, which well correlated with the induction of apoptosis of HaCaT cells. To investigate the role of clusterin/apoliporotein J in ropivacaine-induced apoptosis,HaCaT cells overexpressing clusterin/apoliporotein J were generated and compared to cells expressing the well established anti-apoptotic Bcl-2 protein. Ectopic overexpression of the secreted form of clusterin/apoliporotein J or Bcl-2decreased the sensitivity of HaCaT cells to toxic effects of ropivacaine as demonstrated by DNA fragmentation, the proteolytic cleavage of PARP and by a reduction in procaspase-3 expression. Furthermore, the downregulation of endogenous clusterin/apolipoprotein J levels by ropivacaine suggested that this might be one mechanism by which ropivacaine induced cell death in HaCaT cells. In conclusion, the ability of ropivacaine to induce antiproliferative responses and to suppress the expression of the anti-apoptotic protein clusterin/apolipoprotein J, combined with previously reported anti-inflammatory activity and analgesic property of the drug, suggests that ropivacaine may have potential utility in the local treatment of tumors. 相似文献
19.
《Translational oncology》2021,14(11):101198
P-glycoprotein (P-gp) is an adenosine triphosphate (ATP)-dependent drug efflux protein commonly associated with multidrug resistance in cancer chemotherapy. In this report, we used a dual-fluorescent co-culture model to study the population dynamics of the drug sensitive human ovarian cancer cell line (OVCAR-8-DsRed2) and its resistant subline that overexpresses P-gp (NCI/ADR-RES-EGFP) during the course of a photodynamic therapy (PDT)-olaparib combination regimen. Without treatment, OVCAR-8-DsRed2 cells grew more rapidly than the NCI/ADR-RES-EGFP cells. Olaparib treatment reduced the total number of cancer cells by 70±4% but selected for the resistant NCI/ADR-RES-EGFP population since olaparib is an efflux substrate for the P-gp pump. This study used the FDA-approved benzoporphyrin derivative (BPD) photosensitizer or its lipidated formulation ((16:0)LysoPC-BPD) to kill OVCAR-8 cells and reduce the likelihood that olaparib-resistant cells would have selective advantage. Three cycles of PDT effectively reduced the total cell number by 66±3%, while stabilizing the population ratio of sensitive and resistant cells at approximately 1:1. The combination of olaparib treatment and PDT enhanced PARP cleavage and deoxyribonucleic acid (DNA) damage, further decreasing the total cancer cell number down to 10±2%. We also showed that the combination of olaparib and (16:0)LysoPC-BPD-based PDT is up to 18-fold more effective in mitigating the selection of resistant NCI/ADR-RES-EGFP cells, compared to using olaparib and BPD-based PDT. These studies suggest that PDT may improve the effectiveness of olaparib, and the use of a lipidated photosensitizer formulation holds promise in overcoming cancer drug resistance. 相似文献
20.
Yali Li Kyung Jong Won Do Yoon Kim Ha Bin Kim Hye Min Kang Su Yeon Lee Hwan Myung Lee 《化学与生物多样性》2021,18(4):e2001051
Smilax china (SC) has pharmacological effects including anti-inflammatory activity, but its effects on skin wound healing and skin barrier function have not been investigated. Here, we investigated the effects of absolute extracted from SC flowers (SCF) on skin wound healing-linked responses and functional skin barrier proteins using human epidermal keratinocytes (HaCaT cells). SCF absolute contained 20 components and was non-toxic to HaCaT cells. The absolute increased the proliferation, migration, and sprout outgrowth of HaCaT cells, and enhanced the activations of serine/threonine-specific protein kinase and extracellular signal-regulated kinase1/2. In addition, it increased the syntheses of type I and IV collagens and the expressions of skin barrier proteins (filaggrin and loricrin). These results indicate SCF absolute may has positive effects on skin wound healing by accelerating keratinocyte migration and proliferation activities and collagen synthesis, and on skin barrier function by upregulating barrier proteins in keratinocytes. We suggest SCF absolute to be considered as a potential means of promoting skin wound and barrier repair. 相似文献