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ATP-binding cassette (ABC) transporters such as ABCB1, ABCG2, and ABCC1 are the major players in drug efflux-mediated multidrug resistance (MDR), which severely affects the efficacy of chemotherapy. Several synthetic compounds block the drug transport by ABC transporters; however, they exhibit a narrow therapeutic window, and produce side effects in non-target normal tissues. Conversely, the downregulation of the expression of ABC drug transporters seems to be a promising strategy to reverse MDR in cancer cells. Several signaling pathways, such as NF-κB, STAT3, Gli, NICD, YAP/TAZ, and Nrf2 upregulate the expression of ABC drug transporters in drug-resistant cancers. Recently, natural medicinal compounds have gained importance to overcome the ABC drug-efflux pump-mediated MDR in cancer. These compounds target transcription factors and the associated signal transduction pathways, thereby downregulating the expression of ABC transporters in drug-resistant cancer cells. Several potent natural compounds have been identified as lead candidates to synergistically enhance chemotherapeutic efficacy, and a few of them are already in clinical trials. Therefore, modulation of signal transduction pathways using natural medicinal compounds for the reversal of ABC drug transporter-mediated MDR in cancer is a novel approach for improving the efficiency of the existing chemotherapeutics. In this review, we discuss the modulatory role of natural medicinal compounds on cellular signaling pathways that regulate the expression of ABC transporters in drug-resistant cancer cells. • ATP-binding cassette (ABC) transporters are the major players of multidrug resistance (MDR). • Signaling pathways upregulate the expression of ABC drug transporters in drug-resistant cancers. • Downregulation of the expression of ABC drug transporter reverses drug resistance in MDR cancer cells. • Natural medicinal compounds downregulates the expression of ABC transporters in drug-resistant cancer cells. • Natural medicinal compounds could be used as chemosensitizers to overcome ABC transporters mediated drug-resistance. [ABSTRACT FROM AUTHOR]

The gram-positive bacterium Deinococcus radiodurans can survive under extreme ionizing radiation environment. This study aims to rationalize the role of redox balance, antioxidant status, and metabolite content on the radiation survival of D. radiodurans. We found that the TrxR inhibitors, i.e., ebselen, auranofin, and epigallocatechin gallate (EGCG) (10 µM) treatment affects the radiation survival of D. radiodurans. The TrxR inhibitors treatment affects the redox status, activities of antioxidant enzymes, increases the intracellular ROS levels and protein carbonylation upon 4 kGy ionizing radiation treatments. Moreover, the alteration in cellular redox status affects the metabolites content of the organism. In addition, we noticed differential metabolomic profiles in sham control, radiation control (4 kGy), and TrxR inhibitors plus radiation-treated D. radiodurans. The TrxR inhibitors plus radiation treated groups exhibit more variation compare to sham control and 4 kGy radiation-exposed D. radiodurans. Further, some novel metabolites can possess the high antioxidant property and involved in vital cellular metabolism were found in sham control and radiation treated cells of D. radiodurans. Thus, the results illustrate the role of intracellular redox status in the survival and metabolomic profile of D. radiodurans. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the photochemopreventive effects of ferulic acid (FA) against chronic ultraviolet-B (290–320 nm) induced oxidative stress, inflammation and angiogenesis in the skin of Swiss albino mice. Chronic UVB exposure (180 mJ/cm 2 for 30 weeks; thrice in a week) induced tumor formation in the mice skin that showed increased expression of carcinogenic and inflammatory markers when compared with the control animals. The intraperitoneal (FAIP) and topical (FAT) administration of FA significantly reduced the incidence of UVB-induced tumor volume and tumor weight in the mice skin. Histopathological studies revealed that both FAIP and FAT administration prevented the UVB-induced hyperplasia, squamous cell carcinoma (SCC) and dysplastic feature in the mice skin. Further, it has been observed that FA treatment reverted chronic UVB-induced oxidative damage (thiobarbituric acid reactive substances, superoxide dismutase, catalase, glutathione peroxidase) accompanied with modulation of vascular endothelial growth factor ( VEGF ), inducible nitric oxide synthase ( iNOS ), TNF-α and IL-6 in the mice skin tumor. FA treatment also modulates mutated p53 , Bcl-2 and Bax expressions in the UVB-induced mice skin tumor. Thus, the results of the present study indicate ferulic acid has potential against UVB-induced carcinogenesis in the Swiss albino mice. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Solar ultraviolet-B radiation (UVB) has severe adverse effects on the structure and functions of the skin. Although, UVB (290–320 nm) represents only 5–10% of UV light reaching earth's surface, its contribution towards photoaging is tremendous. In this present study was investigate the photoprotective effect of methanolic extract of the male flower of J. regia L. (MEJR) against UVB induced photoaging in human epidermal keratinocytes (HaCaT). Cells were exposed to UVB-irradiation at a dose of 20 mJ/cm2, induces the activation of several signaling pathways which are associated with oxidative stress and photoaging. A single dose of UVB irradiation increased the protein and mRNA expression of MAPKs, AP-1, MMPs, Smad7 and decreased expression of TIMP-1/2, TGF-β1, Smad3, procollagen type-1 in HaCaT cells. In contrast, pretreatment of MEJR (80 μg/ml) prior to UVB-irradiation significantly prevented the overexpression of MAPKs, AP-1, MMPs, Smad7 and decreased expression of TIMP-1/2, TGF-β1, Smad3 and procollagen type-1 in HaCaT cells. Moreover, pretreatment of MEJR (80 μg/ml) prior to UVB-irradiation significantly prevents apoptosis in sub G o -phase. Thus, MEJR protects UVB-mediated photoaging in human skin cells, by modulating the expression of photoaging markers. The protection might be because of the presence of the good amount of bioactive compounds in MEJR. [ABSTRACT FROM AUTHOR]

Exposure to solar ultraviolet-B (UVB) radiation leads to the formation of cyclobutane pyrimidine dimers (CPDs). We investigated the protective effect of apigenin against UVB-induced CPDs formation in human dermal fibroblasts cells (HDFa). For this purpose, HDFa cells were treated with apigenin (15 μM) prior to UVB irradiation (20 mJ/cm 2 ); DNA damage and subsequent molecular end points were observed. Exposure to UVB radiation increased significant CPDs formation in HDFa cells and the frequencies of CPDs were reduced by treatment with apigenin (15 μM). UVB-induced CPDs downregulates the expression of nucleotide excision repair (NER) genes such as xeroderma pigmentosum complementation group C, B, G and F (XPC, XPB, XPG and XPF), transcription factor II human (TFIIH) and excision repair cross-complementation group 1 (ERCC1) in HDFa cells. Conversely, apigenin treatment restored UVB-induced loss of NER proteins in HDFa cells, which indicates its preventive effect against CPDs formation. Besides, single low dose UVB-exposure induced nuclear fragmentation, apoptotic frequency and apoptotic proteins expression (Bax and Caspase-3) have been prevented by the apigenin pretreatment. Furthermore, apigenin exhibits strong UV absorbance property and showed 10.08 SPF value. Thus, apigenin can protect skin cells against UVB-induced CPDs formation probably through its sunscreen effect. Hence, apigenin can be considered as an effective protective agent against UV induced skin damages. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) remains a major obstacle in cancer chemotherapy. The use of the dietary phytochemicals as chemosensitizing agents to enhance the efficacy of conventional cytostatic drugs has recently gained the attention as a plausible approach for overcoming the drug resistance. The aim of this study was to investigate whether a naturally occurring diet-based phenolic acid, ferulic acid, could sensitize paclitaxel efficacy in ABCB1 overexpressing (P-glycoprotein) colchicine selected KB Ch R 8-5 cell line. In vitro drug efflux assays demonstrated that ferulic acid inhibits P-glycoprotein transport function in drug resistant KB Ch R 8-5 cell lines. However, ferulic acid significantly downregulates ABCB1 expression in a concentration dependent manner. Cytotoxicity assay reveals that ferulic acid decreased paclitaxel resistance in KBCh R 8-5 and HEK293/ABCB1 cells, which indicates its chemosensitizing potential. Clonogenic cell survival assay and apoptotic morphological staining further confirm the chemosensitizing potential of ferulic acid in drug resistant KB Ch R 8-5 cell lines. Ferulic acid treatment enhances paclitaxel mediated cell cycle arrest and upregulates paclitaxel-induced apoptotic signaling in KB resistant cells. Hence, it has been concluded that downregulation of ABCB1 and subsequent induction of paclitaxel-mediated cell cycle arrest and apoptotic signaling may be the cause for the chemosensitizing potential of ferulic acid in P-gp overexpressing cell lines. [ABSTRACT FROM AUTHOR]

P-glycoprotein, encoded by ATP-binding cassette transporters B1 gene (ABCB1), renders multidrug resistance (MDR) during cancer chemotherapy. Several synthetic small molecule inhibitors affect P-glycoprotein (P-gp) transport function in MDR tumor cells. However, inhibition of P-gp transport function adversely accumulates chemotherapeutic drugs in non-target normal tissues. Moreover, most small-molecule P-gp inhibitors failed in the clinical trials due to the low therapeutic window at the maximum tolerated dose. Therefore, downregulation of ABCB1 -gene expression (P-gp) in tumor tissues seems to be a novel approach rather than inhibiting its transport function for the reversal of multidrug resistance (MDR). Several plant-derived phytochemicals modulate various signal transduction pathways and inhibit translocation of transcription factors, thereby reverses P-gp mediated MDR in tumor cells. Therefore, phytochemicals may be considered an alternative to synthetic small molecule P-gp inhibitors for the reversal of MDR in cancer cells. This review discussed the role of natural phytochemicals that modulate ABCB1 expression through various signal transduction pathways in MDR cancer cells. Therefore, modulating the cell signaling pathways by phytochemicals might play crucial roles in modulating ABCB1 gene expression and the reversal of MDR. [Display omitted] • P-glycoprotein renders multidrug resistance during cancer chemotherapy. • Inhibition of P-gp transport function adversely accumulates drugs in normal tissues. • Downregulation of P-gp expression in tumor tissues seems to be a novel approach. • Phytochemicals modulate cell signaling pathways; reverses P-gp mediated MDR. • Phytochemicals may be considered an alternative for the reversal of MDR. [ABSTRACT FROM AUTHOR]

• Preparation of self-assembled two opposites charged polysaccharide (fucoidan and chitosan). • Chitosan enhanced intestinal absorption of fuocidan in mice intestine. • Fucoidan are capable of increased protecting the intestinal epithelium from radiation damage. Fucoidan, a sulphated polysaccharide, plays a vital role in reducing cellular oxidative damage by exerting potential antioxidant activity. However, because of the negative surface charges of oligofucoidan, it shows poor oral intestinal absorption. To overcome this drawback, the oligofucoidan polysaccharides self-assembled with opposite charge based polysaccharides (chitosan) to form the chitosan-fucoidan polysaccharides (C 1 -F 3 P) nanoparticles (NPs) of 190–230 nm in size. The oligofucoidan and C 1 -F 3 P NPs were studied for their radioprotective property using mice exposed to 5 Gy radiation. The C 1 -F 3 P NPs prevents radiation induced lipid peroxidation and restores intestinal enzymatic and non-enzymatic antioxidants (p < 0.05) status. In addition, hematoxylin-eosin staining revealed the radioprotective effect of oligofucoidan and C 1 -F 3 P NPs by mitigating the loss of crypt and villi in the small intestine. Thus, the present study demonstrated that C 1 -F 3 P NPs can be considered as a radioprotective agent that can be used for the prevention and treatment of Gy-radiation-induced intestine injury. [ABSTRACT FROM AUTHOR]