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Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
However, analogues of camptothecin such as topotecan and irinotecan were produced to address these issues, and these are now in clinical use for the treatment of a number of cancers including small-cell lung, colon, breast, and melanoma, as well as some leukemias. As a result, topotecan was approved by the FDA in 1996 for the treatment of advanced ovarian cancers resistant to other chemotherapeutic agents. The injectable irinotecan hydrochloride was also approved in 1996 as a treatment for metastatic cancer of the colon or rectum in patients not responding to standard treatment with fluorouracil.
An Introduction to the Ethnopharmacology of Wild Plants
Published in Mahendra Rai, Shandesh Bhattarai, Chistiane M. Feitosa, Ethnopharmacology of Wild Plants, 2021
Shandesh Bhattarai, Christiane Mendes Feitosa, Mahendra Rai
The first agents to advance into clinical use were the isolation of the vinca alkaloids, vinblastine, and vincristine from Catharanthus roseus, for the treatment of cancer followed by the discovery of paclitaxel from Taxus brevifolia (Kinghorn 1994, Kaur et al. 2011). Various parts of the Taxus have been used for the treatment of some noncancerous cases (Crag and Newmann 2005). Taxus baccata was also reported for the treatment of cancer. Paclitaxel is significantly active against ovarian cancer, advanced breast cancer, and lung cancer. Topotecan is used for ovarian and lung cancer from Xi shu tree [Camptotheca acuminata] (Steenhuysen 2007). Camptothecin, isolated from Camptotheca acuminate, is used for the treatment of ovarian and small cell lung cancers, and colorectal cancers (Kinghorn 1994, Creemer et al. 1996, Bertino 1997). Irinotecan is used for colon cancer treatment from Xishu tree [Camptotheca acuminate] (Online Medical Dictionary 2007). Epipodophyllotoxin was isolated as the active antitumor agent from the roots of Podophyllum species, Podophyllum peltatum and Podophyllum emodi, used in the treatment of lymphomas and bronchial and testicular cancers (Harvey 1999). The Podophyllum peltatum and P. emodii are used for the skin cancers.
Investigational Nanomedicines in 2016: A Review of Nanotherapeutics Currently Undergoing Clinical Trials *
Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Joseph M. Caster, Artish N. Patel, Tian Zhang, Andrew Wang
Camptothecin is a topoisomerase I inhibitor which has potent antineoplastic activity but has had very little clinical translation because of significant systemic toxicities. Campothecin is thus a prime candidate for nanoformulation. A drug-conjugate formulation of camptothecin and a cyclodextran-PEG polymer, marketed as CRLX-101 (formerly IT-101, Cerulean Pharma, Inc.) has shown promising preclinical and early clinical results [28–30]. There are a number of phase I/II studies utilizing CRLX-101 alone or in combination with other drugs in a number of clinical settings including RCC, NSCLC, gyn malignancies, and esophageal tumors. CRLX-101 has also been evaluated for use as a radiosensitizer with capecitabine as neoadjuvant multimodality therapy for advanced rectal cancers. A completed phase 1 study demonstrated a favorable toxicity profile, and phase II studies are ongoing.
Carbon-based nanomaterials for targeted cancer nanotherapy: recent trends and future prospects
Published in Journal of Drug Targeting, 2021
Mohaddeseh Sajjadi, Mahmoud Nasrollahzadeh, Babak Jaleh, Ghazaleh Jamalipour Soufi, Siavash Iravani
rGO was decorated with magnetic NPs and camptothecin drug, followed by the connection of 4-hydroxy coumarin (4-HC) to rGO by allylamine (AA) linker [211]. MTT assay showed that free camptothecin had higher toxic effects on normal cells due to damaging the DNA. The introduced nanocarrier had no significant toxic effects on the healthy cells (WS-1 cells) while showing good biocompatibility. The cell viability was about 75% in 100 µg mL−1 after 24 h of treatment. UV-Vis irradiation at a wavelength of >365nm was used for the PDT process and a cancer cell viability of 38% was achieved after PDT [211]. In addition, gold nanorods (GNRs) were loaded onto the surface of GO by applying polydopamine (PDA) to prepare GNRs/GO@PDA hybrid nanosheets for targeted DOX drug delivery [212]. The designed nanosheets displayed low cytotoxicity even at a concentration of 250 µg mL−1 after 48 h of treatment and excellent biocompatibility [212]. Furthermore, fluorinated graphene was fabricated by green method and employed as a nanocarrier for the delivery of curcumin to the cancer cells [213]. It was revealed that the toxic effect was dependent on the sample concentration and the nanocarrier showed good biocompatibility in the concentration range of 100–500 µg mL−1 (Figure 14(a,b)). In addition, the confocal spectroscopy images of the FG-curcumin sample showed blue and red emission from the nuclei of cancer cells due to FG carrier and curcumin drug, respectively, after 12 h treatment (Figure 14(c,d)) [213].
Recent progress and challenges in drug development to fight hand, foot and mouth disease
Published in Expert Opinion on Drug Discovery, 2020
Ze Qin Lim, Qing Yong Ng, Justin Wei Qing Ng, Vikneswari Mahendran, Sylvie Alonso
In a separate study, screening of the same natural product library identified Camptothecin as a potential hit [84]. Camptothecin was found to reduce EV-A71 replication through inhibition of the mammalian DNA Topoisomerase I (TOP1), which interacts directly with the viral RNA-dependent RNA polymerase 3D. This study described for the first time that TOP1 translocates from the nucleus to the cytoplasm during EV-A71 infection, and co-localizes with viral replication vesicles [84]. This suggests that TOP1 represents a druggable host target to impair EV-A71 infection cycle. However, similar to Auraptene, Formononetin, and Yangonin, Camptothecin did not exhibit complete EV-A71 inhibition even at the highest tested concentrations [84]. A combination therapy approach may be considered since these compounds have different targets. In addition to improve the killing efficacy, such approach may also address the potential rise of drug-resistance [85]. Nevertheless, the in vivo efficacy of these four natural compounds as well as their safety profile remain to be established and reported.
Phyla nodiflora L. Extracts Induce Apoptosis and Cell Cycle Arrest in Human Breast Cancer Cell Line, MCF-7
Published in Nutrition and Cancer, 2019
Peik Lin Teoh, Monica Liau, Bo Eng Cheong
In this study, we only focused on three extracts of P. nodiflora: leaf ethyl acetate (EA leaf), stem ethyl acetate (EA stem) and stem methanol (Met stem) extracts. Their anti-proliferative activities on MCF-7 and MCF10A were determined using MTT assay. The three extracts exhibited growth inhibition on MCF-7 in a dose-dependent manner (Fig. 1A). The inhibitory effect is selective towards MCF-7 cells with a minimal inhibitory effect on normal MCF10A cells at the range of concentrations tested (Fig. 1B). In contrast, camptothecin, an anticancer drug was found to inhibit both normal and cancer cells significantly (Fig. 1C). Both EA extracts were found to have more potent effect on cancer cells when compared to Met stem extract. The magnitude of antiproliferative activity against MCF-7 cell is EA leaf > EA stem > Met stem with the IC50 values of 44.02 ± 0.42 µg/mL, 57.27 ± 0.11 µg/mL and 96.26 ± 0.43 µg/mL, respectively.