Topical Collection "Anticancer Drug Discovery and Development"
Prof. Dr. Hidayat Hussain
Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120 Halle (Salle), Germany
natural product chemistry; medicinal chemistry; cancer biology; bioorganic chemistry; pharmacology; diabetes; synthetic chemistry; biology-oriented synthesis
Special Issues and Collections in MDPI journals
Topical Collection Information
Cancer is a world health issue and affects all communities around the globe and this disease is the second leading cause of death globally. Moreover, there has been continued progress in anticancer drug development in the last few years. New anticancer agents have been approved for cancer treatment but majority of these approved molecules have serious adverse side effects. This illustrates that there is still an urgent need for the development of novel anti-cancer drugs with a unique mechanism of action.
The focus of this Special Issue is on Natural products (NPs)-based anticancer molecules, and synthetic anticancer compounds. Notably, this issue will also emphasis on the relationship between the chemical structure and the biological activity of the molecules along with appplication of bioinformatics in cancers. Furthermore, this Special Issue also wellcome articles anticancer effects as vascular targeting agents, tubulin inhibitors, and topoisomerase targeting agents. In addition, this Special Issue will also focus on the development of new therapeutic agents for cancer treatment, employing the newest techniques of pharmacology, biotechnology, and genetic engineering. This Issue welcomes original articles, communications and reviews dealing with the cancer treatment.
Prof. Dr. Hidayat Hussain
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- Anticancer Natural products
- Anticancer synthetic compounds
- Mode of action
- Drug resistance
- Tubulin inhibitors
- Topoisomerase inhibitors
- Tumor cells
Published Papers (5 papers)
Melatonin Suppresses Oral Squamous Cell Carcinomas Migration and Invasion through Blocking FGF19/FGFR 4 Signaling Pathway
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Oral squamous cell carcinomas (OSCCs) are one of the most prevalent malignancies, with a low five-year survival rate, thus warranting more effective drugs or therapy to improve treatment outcomes. Melatonin has been demonstrated to exhibit oncostatic effects. In this study, we explored the
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Oral squamous cell carcinomas (OSCCs) are one of the most prevalent malignancies, with a low five-year survival rate, thus warranting more effective drugs or therapy to improve treatment outcomes. Melatonin has been demonstrated to exhibit oncostatic effects. In this study, we explored the anti-cancer effects of melatonin on OSCCs and the underlying mechanisms. A human tongue squamous cell carcinoma cell line (SCC-15) was treated with 2 mM melatonin, followed by transwell migration and invasion assays. Relative expression levels of Fibroblast Growth Factor 19 (FGF19) was identified by Cytokine Array and further verified by qPCR and Western blot. Overexpression and downregulation of FGF19 were obtained by adding exogenous hFGF19 and FGF19 shRNA lentivirus, respectively. Invasion and migration abilities of SCC-15 cells were suppressed by melatonin, in parallel with the decreased FGF19/FGFR4 expression level. Exogenous hFGF19 eliminated the inhibitory effects of melatonin on SCC-15 cells invasion and migration, while FGF19 knocking-down showed similar inhibitory activities with melatonin. This study proves that melatonin suppresses SCC-15 cells invasion and migration through blocking the FGF19/FGFR4 pathway, which enriches our knowledge on the anticancer effects of melatonin. Blocking the FGF19/FGFR4 pathway by melatonin could be a promising alternative for OSCCs prevention and management, which would facilitate further development of novel strategies to combat OSCCs.
Development of MRI-Detectable Boron-Containing Gold Nanoparticle-Encapsulated Biodegradable Polymeric Matrix for Boron Neutron Capture Therapy (BNCT)
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This study aimed to develop a novel magnetic resonance imaging (MRI)-detectable boron (B)-containing nanoassemblies and evaluate their potential for boron neutron capture therapy (BNCT). Starting from the citrate-coated gold nanoparticles (AuNPs) (23.9 ± 10.2 nm), the diameter of poly (D, L-lactide-co-glycolide) AuNPs (PLGA-AuNPs)
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This study aimed to develop a novel magnetic resonance imaging (MRI)-detectable boron (B)-containing nanoassemblies and evaluate their potential for boron neutron capture therapy (BNCT). Starting from the citrate-coated gold nanoparticles (AuNPs) (23.9 ± 10.2 nm), the diameter of poly (D, L-lactide-co-glycolide) AuNPs (PLGA-AuNPs) increased approximately 110 nm after the encapsulation of the PLGA polymer. Among various B drugs, the self-produced B cages had the highest loading efficiency. The average diameter of gadolinium (Gd)- and B-loaded NPs (PLGA-Gd/B-AuNPs) was 160.6 ± 50.6 nm with a B encapsulation efficiency of 28.7 ± 2.3%. In vitro MR images showed that the signal intensity of PLGA-Gd/B-AuNPs in T1-weighted images was proportional to its Gd concentration, and there exists a significantly positive relationship between Gd and B concentrations (R2
= 0.74, p
< 0.005). The hyperintensity of either 250 ± 50 mm3
(larger) or 100 ± 50 mm3
(smaller) N87 xenograft was clearly visualized at 1 h after intravenous injection of PLGA-Gd/B-AuNPs. However, PLGA-Gd/B-AuNPs stayed at the periphery of the larger xenograft while located near the center of the smaller one. The tumor-to-muscle ratios of B content, determined by inductively coupled plasma mass spectrometry, in smaller- and larger-sized tumors were 4.17 ± 1.42 and 1.99 ± 0.55, respectively. In summary, we successfully developed theranostic B- and Gd-containing AuNPs for BNCT in this study.
In Search of Effective Anticancer Agents—Novel Sugar Esters Based on Polyhydroxyalkanoate Monomers
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Cancer is one of the deadliest illness globally. Searching for new solutions in cancer treatments is essential because commonly used mixed, targeted and personalized therapies are sometimes not sufficient or are too expensive for common patients. Sugar fatty acid esters (SFAEs) are already
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Cancer is one of the deadliest illness globally. Searching for new solutions in cancer treatments is essential because commonly used mixed, targeted and personalized therapies are sometimes not sufficient or are too expensive for common patients. Sugar fatty acid esters (SFAEs) are already well-known as promising candidates for an alternative medical tool. The manuscript brings the reader closer to methods of obtaining various SFAEs using combined biological, chemical and enzymatic methods. It presents how modification of SFAE’s hydrophobic chains can influence their cytotoxicity against human skin melanoma and prostate cancer cell lines. The compound’s cytotoxicity was determined by an MTT assay, which followed an assessment of SFAEs’ potential metastatic properties in concentrations below IC50
values. Despite relatively high IC50
values (63.3–1737.6 μM) of the newly synthesized SFAE, they can compete with other sugar esters already described in the literature. The chosen bioactives caused low polymerization of microtubules and the depolymerization of actin filaments in nontoxic levels, which suggest an apoptotic rather than metastatic process. Altogether, cancer cells showed no propensity for metastasis after treating them with SFAE. They confirmed that lactose-based compounds seem the most promising surfactants among tested sugar esters. This manuscript creates a benchmark for creation of novel anticancer agents based on 3-hydroxylated fatty acids of bacterial origin.
Proteomics Analysis of Andrographolide-Induced Apoptosis via the Regulation of Tumor Suppressor p53 Proteolysis in Cervical Cancer-Derived Human Papillomavirus 16-Positive Cell Lines
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Regardless of the prophylactic vaccine accessibility, persistent infections of high-risk human papillomaviruses (hr-HPVs), recognized as an etiology of cervical cancers, continues to represent a major health problem for the world population. An overexpression of viral early protein 6 (E6) is linked to carcinogenesis.
[...] Read more.
Regardless of the prophylactic vaccine accessibility, persistent infections of high-risk human papillomaviruses (hr-HPVs), recognized as an etiology of cervical cancers, continues to represent a major health problem for the world population. An overexpression of viral early protein 6 (E6) is linked to carcinogenesis. E6 induces anti-apoptosis by degrading tumor suppressor proteins p53 (p53) via E6-E6-associated protein (E6AP)-mediated polyubiquitination. Thus, the restoration of apoptosis by interfering with the E6 function has been proposed as a selective medicinal strategy. This study aimed to determine the activities of andrographolide (Androg) on the disturbance of E6-mediated p53 degradation in cervical cancer cell lines using a proteomic approach. These results demonstrated that Androg could restore the intracellular p53 level, leading to apoptosis-induced cell death in HPV16-positive cervical cancer cell lines, SiHa and CaSki. Mechanistically, the anti-tumor activity of Androg essentially relied on the reduction in host cell proteins, which are associated with ubiquitin-mediated proteolysis pathways, particularly HERC4 and SMURF2. They are gradually suppressed in Androg-treated HPV16-positive cervical cancer cells. Collectively, the restoration of p53 in HPV16-positive cervical cancer cells might be achieved by disruption of E3 ubiquitin ligase activity by Androg, which could be an alternative treatment for HPV-associated epithelial lesions.
Anticancer Activity of Two Novel Hydroxylated Biphenyl Compounds toward Malignant Melanoma Cells
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Melanoma, the deadliest form of skin cancer, is still one of the most difficult cancers to treat despite recent advances in targeted and immune therapies. About 50% of advanced melanoma do not benefit of such therapies, and novel treatments are requested. Curcumin and
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Melanoma, the deadliest form of skin cancer, is still one of the most difficult cancers to treat despite recent advances in targeted and immune therapies. About 50% of advanced melanoma do not benefit of such therapies, and novel treatments are requested. Curcumin and its analogs have shown good anticancer properties and are being considered for use in combination with or sequence to recent therapies to improve patient outcomes. Our group previously published the synthesis and anticancer activity characterization of a novel curcumin-related compound against melanoma and neuroblastoma cells (D6). Here, two hydroxylated biphenyl compounds—namely, compounds 11
—were selected among a small collection of previously screened C2-symmetric hydroxylated biphenyls structurally related to D6 and curcumin, showing the best antitumor potentiality against melanoma cells (IC50
values of 1.7 ± 0.5 μM for 11
and 2.0 ± 0.7 μM for 12
) and no toxicity of normal fibroblasts up to 32 µM. Their antiproliferative activity was deeply characterized on five melanoma cell lines by performing dose-response and clonal growth inhibition assays, which revealed long-lasting and irreversible effects for both compounds. Apoptosis induction was ascertained by the annexin V and TUNEL assays, whereas Western blotting showed caspase activation and PARP cleavage. A cell cycle analysis, following cell treatments with either compound 11
, highlighted an arrest in the G2/M transition. Taking all this evidence together, 11
were shown to be good candidates as lead compounds to develop new anticancer drugs against malignant melanoma.