Article
Chemistry, Medicinal
Svetlana Paskas, Philipp Stockmann, Sanja Mijatovic, Lydia Kuhnert, Walther Honscha, Evamarie Hey-Hawkins, Danijela Maksimovic-Ivanic
Summary: The ABCG2 transporter protein plays an important role in multidrug resistance and targeting its activity can improve cancer therapies. This study evaluates potential inhibitors of ABCG2 and their toxicity towards cancer cells expressing ABCG2. The results show that some inhibitors can increase the efficacy of therapeutic agents through synergistic effects, and suggest the possible targeting of both ABCG2 and ABCB1 transporters.
Review
Biochemistry & Molecular Biology
Hattie M. Foster, McKenzie N. Carle, Lukas R. Jira, David W. Koh
Summary: The transient receptor potential melastatin (TRPM) subfamily, containing eight known members, plays a significant role in melanoma progression, treatment, and prognosis. Initially identified in cancerous tissue, TRPM involvement in cancer progression and tumorigenesis was investigated. In skin cancer, several TRPM members have been found to play important roles in progression, growth, and patient prognosis. TRPM2, a unique member, shows promising potential in melanoma treatment. Increased TRPM2 expression levels have been observed in melanoma, with important functions in growth, proliferation, and survival. TRPM2 antagonism may offer a new treatment option for melanoma patients in the future.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Analytical
Han Li, Jiaojiao Li, Meng Wang, Weiyue Feng, Fuping Gao, Ying Han, Yijie Shi, Zhongying Du, Qing Yuan, Peng Cao, Xiayan Wang, Xueyun Gao, Kai Cao, Liang Gao
Summary: Identifying effective reversal agents to overcome multidrug resistance is crucial for improving tumor chemotherapy. In this study, a metal cluster-based probe called clusterbody was developed for flow sorting-assisted single-cell mass spectrometry analysis. The clusterbody, synthesized through biomimetic mineralization, selectively recognizes an efflux pump protein and enables high-throughput cell sorting based on fluorescence emitted by the probe. Protein abundance at the single-cell level is determined through precise signal amplification using laser ablation inductively coupled plasma mass spectrometry, allowing quantitative evaluation of reversal agent treatment. This work provides a new approach to identify reversal agents and sheds light on developing combined or synergetic tumor therapy.
ANALYTICAL CHEMISTRY
(2023)
Article
Oncology
Maciej Sobczak, Magdalena Strachowska, Karolina Gronkowska, Agnieszka Robaszkiewicz
Summary: In this research, the CoREST complex is identified as a key factor that controls the expression of ABC transporters in cisplatin-treated cancer cells, preventing multidrug resistance. The CoREST complex occupancy at gene promoters suppresses the EP300-dependent increase in ABCC transcription induced by cisplatin and gene overexpression in cisplatin-resistant phenotypes. The EP300-mediated activation of ABCC10 in response to cisplatin is only possible in the presence of p53.
Article
Cell Biology
Wanlu Du, Mingxue Gu, Meiqin Hu, Prateeksunder Pinchi, Wei Chen, Michael Ryan, Timothy Nold, Ahmed Bannaga, Haoxing Xu
Summary: During tumor progression, lysosome function is often maladaptively upregulated to meet the high energy demand needed for cancer cell hyper-proliferation and invasion. In metastatic melanoma cells, TRPML1 is dramatically upregulated, and its synthetic agonists can induce necrotic cell death specifically in these cells. This cell death is caused by mitochondria swelling and dysfunction leading to ATP depletion.
Article
Biochemistry & Molecular Biology
Iwona Karwaciak, Anna Salkowska, Kaja Karas, Jaroslaw Dastych, Marcin Ratajewski
Summary: Melanoma cells are resistant to most anticancer chemotherapeutics, but inhibition of SIRT2 can increase sensitivity to cisplatin, reduce cell signaling pathways, and improve the efficacy of cisplatin against melanoma cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Marie-Christin Barth, Norman Haefner, Ingo B. B. Runnebaum, Wolfgang Weigand
Summary: The research explores the anticancer potential of platinum(IV) complexes and investigates the effects of non-steroidal anti-inflammatory drug (NSAID) ligands on their cytotoxicity. The synthesis and characterization of nine platinum(IV) complexes are presented, and their cytotoxic activity is evaluated against ovarian carcinoma cell lines. The most promising complex, Compound 7, induces cell cycle arrest and apoptosis or necrosis in a cell line-dependent manner, acting through a stress response pathway involving p21, CHOP, and ATF3 genes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Simona Laurino, Mariarita Brancaccio, Tiziana Angrisano, Giovanni Calice, Sabino Russi, Pellegrino Mazzone, Giuseppina Di Paola, Michele Aieta, Vitina Grieco, Gabriella Bianchino, Geppino Falco, Tiziana Notarangelo
Summary: Gastric cancer, a leading cause of death globally, is difficult to treat with chemotherapy due to multidrug resistance. This study investigated the role of STAT3 in gastric cancer drug efficiency through gene expression analysis. The study found that gastric cancer cells become resistant to chemotherapy by activating alternative signaling pathways. However, inhibiting IL-6/STAT3 in combination with cisplatin treatment prevented STAT3 activation and increased lethality compared to single-agent treatment. This suggests that IL-6/STAT3 axis blockage may be a strategy to overcome resistance.
Article
Multidisciplinary Sciences
Zuxiong Tang, Jun He, Jiayue Zou, Shufei Yu, Xiaoming Sun, Lei Qin
Summary: The study found that exosomes derived from HepG2/DDP cells can transfer cisplatin resistance to HepG2 and other HCC cell lines, offering new insights into improving the effectiveness of cisplatin in treating HCC.
Review
Biochemistry & Molecular Biology
Linyinxue Dong, Ceeane Paul Dagoc Vargas, Xuechen Tian, Xiayu Chu, Chenqi Yin, Aloysius Wong, Yixin Yang
Summary: Melanoma, a highly malignant skin cancer, has shown resistance to treatments. Recent studies have made significant progress in understanding non-apoptotic cell death processes, such as pyroptosis, ferroptosis, necroptosis, and cuproptosis. This article provides an overview of the mechanisms and signaling pathways involved in non-apoptotic cell death in melanoma, as well as the interplay with apoptosis and autophagy. Importantly, it discusses the potential targeting of non-apoptotic cell death as a promising therapeutic strategy for drug-resistant melanoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Wen-Jun Liu, Peng-yu Pan, Ye Sun, Jian-bo Wang, Huan Zhou, Xin Xie, Zhi-yuan Duan, Han-yu Dong, Wen-na Chen, Li-de Zhang, Chun Wang
Summary: This study reveals the adaptive responses of cisplatin-resistant NSCLC cells to glutamine starvation and suggests that the iron chelator DFO can suppress the growth of these resistant cells through autophagic cell death and apoptosis.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jie He, Jili Chen, Jianfeng Shen
Summary: In this study, the anti-parasitic drug selamectin was identified through drug repositioning analysis as a potential agent to enhance the sensitivity of uveal melanoma (UM) cells to cisplatin. The combination of selamectin and cisplatin showed a synergistic effect in inhibiting UM cell growth and reducing tumor growth in mice. Selamectin achieved these effects by inhibiting autophagy and downregulating cisplatin resistance-associated genes.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Oncology
Minsu Jang, Rackhyun Park, Yea-In Park, Yeonjeong Park, Jin Lee, Sim Namkoong, Eun-Ju Lee, Junsoo Park
Summary: In this study, the regulation of LNX1 expression was investigated, showing decreased expression by DNA damage, including cisplatin, and increased expression by lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA). Increased LNX1 levels were associated with cell-cycle progression and resistance to cisplatin-induced cell death. These findings suggest a role for LNX1 in regulating the cell cycle and contributing to chemoresistance.
Editorial Material
Oncology
Inna Smalley, Keiran S. M. Smalley
Summary: In this study, the authors used RNA sequencing and multiplexed IHC to analyze the spatial immune landscape of melanoma patients. They found that the spatial interaction between cytotoxic T cells and M1-like macrophages expressing PD-L1 can predict the response to immune checkpoint inhibition.
Article
Biochemistry & Molecular Biology
Armelle T. Mbaveng, Cedric G. T. Noulala, Anne R. M. Samba, Simplice B. Tankeo, Sara Abdelfatah, Ghislain W. Fotso, Emmanuel N. Happi, Bonaventure T. Ngadjui, Veronique P. Beng, Victor Kuete, Thomas Efferth
Summary: The cytotoxic potential of the naturally occurring indoloquinazoline alkaloid SCHL was evaluated on a broad panel of animal and human cancer cell lines. SCHL exhibited cytotoxic effects against various cancer cell lines and induced apoptosis, ferroptosis, and necroptosis. Further research on SCHL may lead to the development of a novel drug for combating cancers, including refractory phenotypes.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Article
Cell Biology
Wojciech Szlasa, Sylwester Slusarczyk, Izabela Nawrot-Hadzik, Renata Abel, Aleksandra Zalesinska, Anna Szewczyk, Natalia Sauer, Robert Preissner, Jolanta Saczko, Marcin Drag, Marcin Poreba, Malgorzata Daczewska, Julita Kulbacka, Malgorzata Drag-Zalesinska
Summary: Betulinic acid and betulin are compounds with anti-inflammatory properties and have the potential to reduce inflammation by reducing IL-6 secretion. They have minimal effect on COX-2 activity. Bet-Orn and Bet-Lys are highly cytotoxic and induce the aggregation of IFN gamma R. Bet-Lys has a higher degree of inhibition on COX-2 activity than dexamethasone. Bet-Orn is the only compound that increases the content of HSP-70 in macrophages. All compounds are more effective than dexamethasone in reducing IL-6.
Article
Multidisciplinary Sciences
Wojciech Szlasa, Olga Michel, Natalia Sauer, Vitalij Novickij, Damian Lewandowski, Paulina Kasperkiewicz, Mounir Tarek, Jolanta Saczko, Julita Kulbacka
Summary: This study investigates the effects of nanosecond pulsed electric fields (nsPEF) on pancreatic cancer cells and their mechanisms of action. It reveals that nsPEF treatment leads to the release of microvesicles, enhanced electropermeabilization, and cell shrinkage. It also shows that nsPEF treatment reduces tumor spheroid size and proposes a mechanism involving cell membrane surface tension and actin fiber organization.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Multidisciplinary
Joanna Tunikowska, Nina Rembialkowska, Olga Michel, Justyna Maczynska, Agnieszka Antonczyk, Przemyslaw Przadka, Zdzislaw Kielbowicz, Julita Kulbacka
Summary: This study proposes the combination of indocyanine green (ICG) with bleomycin (BLM) for electrochemotherapy (ECT), which allows for drug distribution control and detection. The method was validated through in vitro and in vivo experiments, demonstrating its safety and effectiveness.
APPLIED SCIENCES-BASEL
(2023)
Review
Biochemistry & Molecular Biology
Julia Karska, Szymon Kowalski, Jolanta Saczko, Mihaela G. G. Moisescu, Julita Kulbacka
Summary: Mechanical forces are essential elements in the world around us, and they have observable effects at both macro and molecular levels. The presence of mechanosensitive ion channels (MIChs), such as the Piezo and TRP families, plays a major role in the tissues and cells of animals, contributing to various physiological processes in the human body. Recent research has also connected these channels to the development of malignant tumors.
Article
Engineering, Biomedical
Zbigniew Raszewski, Katarzyna Chojnacka, Julita Kulbacka, Marcin Mikulewicz
Summary: The aim of this study was to develop a 3D printing material with bioactive properties for producing transparent removable orthodontic appliances. By adding four bioactive glasses at 10% concentration to acrylic monomers, ions such as Ca, P, Si, and F were released. The printed materials were tested for various properties including flexural strength, sorption and solubility, ion release, and cytotoxicity. The results showed that the material released Ca2+ and PO43- ions for 42 days and had good flexural strength in certain orientations. Furthermore, cell survival rate was high after exposure to the material.
JOURNAL OF FUNCTIONAL BIOMATERIALS
(2023)
Article
Biochemistry & Molecular Biology
Julita Kulbacka, Anna Choromanska, Anna Szewczyk, Olga Michel, Dagmara Baczynska, Andrzej Sikora, Joanna Rossowska, Marek Kulbacki, Nina Rembialkowska
Summary: Ultrashort electric pulses in the nanosecond range can affect cell structures and functioning by altering calcium levels. This study examined the impact of nsPEFs combined with calcium on human colon adenocarcinoma cell lines. The results showed that nsPEF with calcium was cytotoxic for drug resistant cancer cells and safe for normal cells. The treatment also caused oxidative stress and altered cell morphology.
BIOELECTROCHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Agnieszka Gajewska-Naryniecka, Urszula Szwedowicz, Zofia Lapinska, Julia Rudno-Rudzinska, Wojciech Kielan, Julita Kulbacka
Summary: Pancreatic cancer is a silent and aggressive disease that only shows symptoms in advanced stages. The only curative treatment is surgical resection, but irreversible electroporation (IRE) offers hope for patients with unresectable tumors. IRE is an ablation therapy that uses high-voltage electrical pulses to destroy cancer cells. This review summarizes the applications and potential of IRE in treating pancreatic cancer, including its combination with drugs or standard treatments. However, further research is needed to assess its effectiveness in humans and understand its full potential.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Szymon Kowalski, Julia Karska, Zofia Lapinska, Bartosz Hetnal, Jolanta Saczko, Julita Kulbacka
Summary: Regulated cell death is a vital and diverse process in organism's life cycle, involving embryonic development, aging, homeostasis regulation, and organ maintenance. This review aims to present the latest literature on pyroptosis and apoptosis, and compare their molecular pathway elements and significance in organism's physiology and pathophysiology.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Ewa Sawicka, Julita Kulbacka, Malgorzata Drag-Zalesinska, Arkadiusz Wozniak, Agnieszka Piwowar
Summary: The number of risk factors for breast cancer is increasing, including estrogens and interaction with toxic chromium(VI). The study investigated the effects of estrogens and Cr(VI) on cell viability and DNA damage. The results showed that 17 beta-E2 had a protective effect against Cr(VI)-induced cytotoxicity.
Article
Pharmacology & Pharmacy
Eivina Radzeviciute-Valciuke, Jovita Gecaite, Augustinas Zelvys, Aukse Zinkeviciene, Rokas Zalneravicius, Veronika Malysko-Ptasinske, Ausra Nemeikaite-Ceniene, Vytautas Kaseta, Natalija German, Jurij Novickij, Almira Ramanaviciene, Julita Kulbacka, Vitalij Novickij
Summary: This study demonstrates that MHz frequency bursts of nanosecond pulses can enhance gene delivery and investigates the potential of gold nanoparticles in this process. The combination of microsecond pulses and gold nanoparticles significantly improves gene delivery, depending on the surface charge and size of the nanoparticles. Gold nanoparticles are ineffective in nanosecond pulse treatment, but MHz pulse treatment remains competitive, with high gene delivery efficiency, low reactive oxygen species generation, preserved cellular viability, and easier operation.
Article
Chemistry, Medicinal
Katarzyna Biezunska-Kusiak, Julita Kulbacka, Anna Choromanska, Nina Rembialkowska, Olga Michel, Jolanta Saczko
Summary: Breast cancer is one of the most common malignant neoplasms in Poland. The use of calcium ion-assisted electroporation has been proven effective in recent studies. This research aimed to investigate the antitumor effects of electroporation and calcium ion-assisted electroporation on human mammary adenocarcinoma cells. The obtained results confirmed the effectiveness of the investigated therapeutic method, providing a basis for further in vivo research and the development of a more effective and safer treatment for breast cancer patients.
Article
Pharmacology & Pharmacy
Nina Rembialkowska, Vitalij Novickij, Eivina Radzeviciute-Valciuke, Egle Mickeviciute, Agnieszka Gajewska-Naryniecka, Julita Kulbacka
Summary: Electrochemotherapy combines anticancer drugs with electroporation to overcome drug resistance in cancer. The study found that different drug combinations can have synergistic effects and that nanosecond pulses provide more flexibility in cancer cell death.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Chemistry, Medicinal
Natalia Sauer, Wojciech Szlasa, Anna Szewczyk, Vitalij Novickij, Jolanta Saczko, Dagmara Baczynska, Malgorzata Daczewska, Julita Kulbacka
Summary: This study investigated the effects of nanosecond pulsed electric field (nsPEF) treatment on melanoma cells and found that it enhanced membrane permeabilization, increased PD-1 checkpoint receptor expression, and promoted potential co-localization or clustering of MHC class II and PD-1 molecules on the cell surface. The treatment also led to cytokine secretion. These findings suggest that nsPEF could be a viable approach to enhance therapeutic agent delivery and modulate the tumor microenvironment to promote an antitumor immune response.