Article
Biochemistry & Molecular Biology
Genoveffa Nuzzo, Carmela Gallo, Fabio Crocetta, Lucia Romano, Giusi Barra, Giuseppina Senese, Mario dell'Isola, Dalila Carbone, Valentina Tanduo, Federica Albiani, Guido Villani, Giuliana d'Ippolito, Emiliano Manzo, Angelo Fontana
Summary: Natural products and their derivatives are important sources for potential drug candidates. Marine natural products (MNPs) are a rich resource with potential pharmacological activities. In this study, a novel bioassay-guided screening platform was developed to identify a new immune-based anticancer compound from MNPs.
Article
Chemistry, Medicinal
Wenjun Wang, Foqing Ma, Yuen Tsz Cheung, Guihua Zeng, Yiqin Zhou, Zijing Chen, Lixin Liang, Tuoping Luo, Rongbiao Tong
Summary: Induction of ferroptosis has been found to be an effective method for cancer treatment. In this study, marine alkaloid lepadins E and H were discovered as new ferroptosis inducers. In vitro experiments showed that lepadins E and H exhibited significant cytotoxicity and induced ferroptosis through the p53-SLC7A11-GPX4 pathway. Animal model studies further confirmed their in vivo antitumor efficacy. This discovery highlights the potential of lepadins as a new class of ferroptosis inducers for anticancer therapy.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Elisabete Lima, Jorge Medeiros
Summary: Marine organisms synthesize various compounds to defend themselves and some of these compounds may have neuroprotective effects. Alzheimer's disease is a complex disease with both genetic and environmental factors, and there is currently no effective treatment. Alkaloids, particularly those with planar structures, halogens, and amine quaternization, may be used against Alzheimer's by reducing its clinical manifestations.
Article
Biochemistry & Molecular Biology
Eslam R. R. El-Sawy, Zeinab A. A. El-Shahid, Ahmed A. F. Soliman, Amr Nassrallah, Ahmed B. B. Abdelwahab, Gilbert Kirsch, Heba Abdelmegeed
Summary: A new series of aplysinopsin analogs were synthesized and their cytotoxic activity against prostate cancer was investigated. Five analogs exhibited high antitumor activity by suppressing the expression of the anti-apoptotic gene Bcl2 and increasing the expression of the pro-apoptotic genes p53, Bax and Caspase 3. The dual mechanism of action via apoptosis and cell cycle arrest induction contributed to the antitumor activity of aplysinopsin analogs. Therefore, these newly synthesized analogs are promising candidates for further preclinical studies against prostate cancer.
Article
Engineering, Biomedical
Jie Li, Wei Tang, Yi Yang, Qing Shen, Yang Yu, Xiaoyou Wang, Yu Fu, Chong Li
Summary: The study introduced the use of natural product Solamargine to design cell-mimicking core-shell nanoparticles with acid-responsive off-coating properties, which showed superior antitumor efficacy in tumor-targeted therapy. This off-coating strategy provides a new perspective for optimizing CM-NPs and highlights the application value of natural product medicines and excipients.
ADVANCED HEALTHCARE MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Conor McCartin, Eric Mathieu, Monique Dontenwill, Christel Herold-Mende, Ahmed Idbaih, Anna Bonfiglio, Matteo Mauro, Sylvie Fournel, Antoine Kichler
Summary: Cancer stem cells (CSCs) are highly resistant to conventional anti-cancer treatments due to their unique characteristics, but their high dependence on mitochondria can be targeted for new therapeutic agents. This study found that a phosphorescent compound showed higher activity against CSCs compared to non-CSCs, with mitochondrial localization and superoxide production confirmed. The findings provide important insights into the potential of this compound for anti-CSC therapeutics.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Multidisciplinary Sciences
Bartosz Wiernicki, Sophia Maschalidi, Jonathan Pinney, Sandy Adjemian, Tom Vanden Berghe, Kodi S. Ravichandran, Peter Vandenabeele
Summary: Ferroptosis, a form of cell death characterized by iron accumulation and lipid peroxidation, has lower immunogenicity compared to other cell death modalities, inhibiting the maturation and antigen cross-presentation of immune cells and hence weakening the anti-tumor immune response.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Maiara M. Romanelli, Maiara Amaral, Fernanda Thevenard, Lucas M. Santa Cruz, Luis O. Regasini, Alvaro E. Migotto, Joao Henrique G. Lago, Andre G. Tempone
Summary: In this study, a new compound BMA was isolated and characterized from a marine coral. It was found that BMA exhibited inhibitory effects against T. cruzi without cytotoxicity to mammalian cells. The mechanism of action of BMA involved the depolarization of mitochondrial membrane potential and reduction of intracellular calcium levels, leading to decreased ATP levels and growth inhibition of T. cruzi.
Article
Pharmacology & Pharmacy
Wenpan Li, Yanhao Jiang, Jianqin Lu
Summary: Tumor immunotherapy, specifically tumor immunogenic cell death (ICD), has shown great potential for cancer therapy. Nanoparticles, such as liposomes, nanostructured lipid carriers, and inorganic nanoparticles, have been widely studied as vehicles for delivering ICD inducers. This review summarizes the strategies of different nanoparticles for ICD-induced cancer immunotherapy and discusses their advantages, disadvantages, and potential solutions. It aims to provide insights into the design of effective nanoparticulate systems for the therapeutic delivery of ICD inducers, ultimately promoting the development of ICD-mediated cancer immunotherapy.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Review
Biochemistry & Molecular Biology
Marie Oliver Metzig, Alexander Hoffmann
Summary: Cell biology research has made significant contributions in improving anti-cancer therapies by studying different forms of regulated cell death, identifying master regulators such as NF kappa B, and translating these findings. In the era of immunotherapy, the targeted induction of immunogenic cell death is becoming increasingly important for optimizing anti-tumor immunity.
Article
Biochemistry & Molecular Biology
Junya Mukomura, Hiroki Nonaka, Hiromasa Sato, Maho Kishimoto, Masayoshi Arai, Naoyuki Kotoku
Summary: This study synthesized and evaluated simplified analogs of marine sponge-derived alkaloid to discover novel anti-mycobacterial substances. The ring truncation effectively reduced cytotoxicity, and the N-(2-arylethyl)quinolin-3-amine skeleton was identified as a promising scaffold for anti-mycobacterial lead compounds.
Review
Biochemistry & Molecular Biology
Darren C. Holland, Anthony R. Carroll
Summary: This article presents a meta-analysis of the biological activities of 2048 marine indole alkaloids (MIAs) and highlights the underexplored bioactivity potentials of most published MIAs. Despite the majority of MIAs not exhibiting cytotoxic or antimicrobial activity, there is still a focus on evaluating structurally related analogues using these assays. Cheminformatics analyses reveal that some MIAs possess potent and diverse activities, and many analogues that were previously only tested in cellular toxicity assays could be better utilized to generate structure-activity relationships for the treatment of emerging diseases. Shifting the focus to non-toxic disease targets could maximize the potential of MIAs for drug discovery.
NATURAL PRODUCT REPORTS
(2023)
Article
Oncology
Philip Vitorino, Chen-Hua Chuang, Alexandre Iannello, Xi Zhao, Wade Anderson, Ronald Ferrando, Zhaomei Zhang, Shravanthi Madhavan, Holger Karsunky, Laura R. Saunders
Summary: Combining sub-efficacious doses of Rova-T with anti-PD1 enhances anti-tumor activity and sustains anti-tumor immunity in SCLC patients. The combination treatment activates immune response, increases CD8 T cells, and results in prolonged anti-tumor effects.
TRANSLATIONAL ONCOLOGY
(2021)
Article
Chemistry, Medicinal
Kai Zhang, Xian Guan, Xiao Zhang, Lu Liu, Ruijuan Yin, Tao Jiang
Summary: Marine alkaloids obtained from sponges have various biological activities and potential medicinal value. Neolamellarin A and its derivatives possess low cytotoxicity and superior neuroprotective activity, suggesting their potential as antagonists against nerve cell apoptosis.
Article
Pharmacology & Pharmacy
Susannah von Hofsten, Manuel K. Langer, Katja Korelin, Synnove Magnussen, Dominik Ausbacher, Trude Anderssen, Tuula Salo, Morten B. Strom, Annette Bayer, Ahmed Al-Samadi, Gerd Berge
Summary: This study explores the anticancer activity of a panel of novel compounds (marine product mimics, MPMs) against head and neck squamous cell carcinoma (HNSCC) cell lines. The results indicate that these novel MPMs are more potent than the previously reported MPM-1 and can activate the integrated stress response associated with immunogenic cell death. Cell surface expression of calreticulin and release of HMGB1 and ATP, hallmarks of immunogenic cell death, were also demonstrated. The MPMs show potential as interesting candidates for future HNSCC cancer therapies.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Hisham F. Bahmad, Houda Samman, Alissar Monzer, Ola Hadadeh, Katia Cheaito, Rana Abdel-Samad, Berthe Hayar, Claudio Pisano, Hiba Msheik, Yen-Nien Liu, Nadine Darwiche, Wassim Abou-Kheir
MOLECULAR CARCINOGENESIS
(2019)
Review
Oncology
M. Akhtar Anwar, Chirine El-Baba, Muhammed H. Elnaggar, Yasmeen O. Elkholy, Mohamed Mottawea, Dina Johar, Tuqa S. Al Shehabi, Firas Kobeissy, Charbel Moussalem, Elie Massaad, Ibrahim Omeis, Nadine Darwiche, A. H. Eid
SEMINARS IN CANCER BIOLOGY
(2020)
Review
Oncology
Charbel K. Moussalem, Elie Massaad, Wassim Baassiri, M. Akhtar Anwar, Firas Kobeissy, Ali Eid, Nadine Darwiche, Ibrahim Omeis
SEMINARS IN CANCER BIOLOGY
(2020)
Review
Genetics & Heredity
Hala Skayneh, Batoul Jishi, Rita Hleihel, Maguy Hamieh, Nadine Darwiche, Ali Bazarbachi, Marwan El Sabban, Hiba El Hajj
Article
Biochemistry & Molecular Biology
Botheina Ghandour, Claudio Pisano, Nadine Darwiche, Ghassan Dbaibo
BIOSCIENCE REPORTS
(2020)
Review
Biochemistry & Molecular Biology
Chirine El-Baba, Amro Baassiri, Georges Kiriako, Batoul Dia, Sukayna Fadlallah, Sara Moodad, Nadine Darwiche
Summary: Terpenoids, the largest class of natural products derived mainly from plants, exhibit diverse anti-tumor effects, including anti-proliferative, apoptotic, anti-angiogenic, and anti-metastatic activities. The complex relationship between apoptosis and autophagy in cancer cells is driven by a delicate balance of protein regulation, leading to different outcomes through interrelated signaling pathways. Further research on autophagy induction by terpenoids may provide insights for novel cancer therapies and more effective treatment regimens.
Article
Biochemistry & Molecular Biology
Lamis Al Aaraj, Berthe Hayar, Zaynab Jaber, Walid Saad, Najat A. Saliba, Nadine Darwiche, Tarek Ghaddar
Summary: The derivatization of Sal-A and Sal-B led to enhanced growth inhibition in the HCT116 cell line model. These novel compounds showed potent anti-growth properties independent of p53 status, suggesting their potential as promising leads for anti-cancer drug design compared to conventional 5-Fluorouracil (5-FU).
Review
Biochemistry & Molecular Biology
Botheina Ghandour, Ghassan Dbaibo, Nadine Darwiche
Summary: The regulation of sphingolipids plays an important role in cancer development and treatment, with ceramide being identified as a key component affecting cell growth, death, and metastasis. Research has shown that retinoids can modulate sphingolipid metabolism and ceramide production, contributing to their efficacy in cancer therapy. Dysregulation of sphingolipids can promote cancer development, while inducing ceramide accumulation can lead to tumor cell death. Resistance to cancer treatment may be due to an imbalance between tumor-suppressor and tumor-promoting sphingolipids, but novel therapeutic interventions targeting these pathways show promise in overcoming this resistance.
BIOCHEMICAL JOURNAL
(2021)
Review
Oncology
Ibrahim AlZaim, Aya Al-Saidi, Safaa H. Hammoud, Nadine Darwiche, Yusra Al-Dhaheri, Ali H. Eid, Ahmed F. El-Yazbi
Summary: As overweight and obesity increase, the number of individuals diagnosed with prostate cancer also rises. The increase in fat tissue can lead to inflammation, which may increase the aggressiveness of prostate cancer. The production of blood clotting factors is also increased in obesity, fat tissue inflammation, and prostate cancer. This article explores the role of these clotting factors in the progression of prostate cancer due to increased body weight and proposes new treatment approaches.
Review
Pharmacology & Pharmacy
Sara Assi, Hiba El Hajj, Berthe Hayar, Claudio Pisano, Walid Saad, Nadine Darwiche
Summary: Retinoids, derived from or related to vitamin A, play crucial roles in regulating various biological processes. They have shown promising anti-cancer effects in preclinical models of different types of cancer. However, their clinical translation has been limited due to various challenges. The development of retinoid delivery systems has been extensively studied to overcome these limitations.
CURRENT DRUG DELIVERY
(2023)
Review
Pharmacology & Pharmacy
Israa A. Cheikh, Chirine El-Baba, Ali Youssef, Najat A. Saliba, Akram Ghantous, Nadine Darwiche
Summary: We evaluated the potential anticancer properties of sesquiterpene lactones (SLs) using cell, animal, and clinical models. Our results highlight the molecular targets and biological mechanisms underlying the therapeutic properties of SLs, as well as their potential for cancer prevention. Additionally, we discussed the structure-activity relationship and pharmacokinetic properties of SLs, and their potential use in combination therapies.
EXPERT OPINION ON DRUG DISCOVERY
(2022)
Article
Oncology
Sadaf Al Hadeethi, Chirine El-Baba, Khaled Araji, Berthe Hayar, Israa Ahmad Cheikh, Riyad El-Khoury, Julnar Usta, Nadine Darwiche
Summary: 5-Fluorouracil (5-FU) has been the preferred treatment for colorectal cancer (CRC) for the past 60 years, but it has high toxicity and drug resistance. Cancer cells have an upregulated pentose phosphate pathway (PPP) which promotes their survival. Recently, mannose has been found to inhibit tumor growth and impair the PPP. In this study, mannose alone or in combination with 5-FU was shown to downregulate the PPP and enhance the sensitivity of CRC cells and tumors to 5-FU. This research could lead to better patient care.
Article
Biochemistry & Molecular Biology
Chirine El-Baba, Zeinab Ayache, Mona Goli, Berthe Hayar, Zeinab Kawtharani, Claudio Pisano, Firas Kobeissy, Yehia Mechref, Nadine Darwiche
Summary: The study shows that ST1926 is effective in reducing cell viability and inducing apoptosis in GBM cells, and it also reduces the level of POLA1 protein. Additionally, proteomics analysis reveals that ST1926 affects multiple cellular processes related to GBM cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Raffaella Cincinelli, Loana Musso, Mario B. Guglielmi, Ilaria La Porta, Alessandra Fucci, Egildo Luca D'Andrea, Francesco Cardile, Fabiana Colelli, Giacomo Signorino, Nadine Darwiche, Silvia Gervasoni, Giulio Vistoli, Claudio Pisano, Sabrina Dallavalle
BIOORGANIC CHEMISTRY
(2020)
Review
Oncology
Nadine Darwiche
AMERICAN JOURNAL OF CANCER RESEARCH
(2020)
