{"title":"Kaempferol Synergistically Enhances Cisplatin-induced Apoptosis and Cell Cycle Arrest in Colon Cancer Cells.","authors":"Muhammad Haroon, Sun Chul Kang","doi":"10.15430/JCP.24.013","DOIUrl":"https://doi.org/10.15430/JCP.24.013","url":null,"abstract":"<p><p>Colon cancer remains a significant global health concern, necessitating the continuous exploration of novel therapeutic strategies. Cisplatin is a first-line chemotherapy medication that is frequently used to treat patients for a variety of malignancies, including colon cancer. However, a major obstacle to its clinical usefulness is acquired resistance. This research investigates the synergistic effects of kaempferol, a natural flavonoid with known anti-cancer properties, in combination with cisplatin, in colon cancer cells. Our study employed colon cancer cell lines to evaluate the individual and combined cytotoxic effects of kaempferol and cisplatin. The results demonstrated a notable enhancement in the cytotoxicity of colon cancer cells when treated with a combination of kaempferol and cisplatin compared to individual treatments. This synergistic effect was further characterized by an increase in apoptosis, as evidenced by morphological changes and biochemical markers of apoptosis and cell cycle. The investigations revealed that the combined treatment led to the modulation of key apoptotic pathways, including the upregulation of pro-apoptotic factors and downregulation of anti-apoptotic factors. Additionally, the synergistic effect was associated with the inhibition of cell proliferation and induction of cell cycle arrest. The findings of this study suggest that the combination of kaempferol and cisplatin holds promise as a potent therapeutic strategy for colon cancer treatment, potentially enhancing the efficacy of conventional chemotherapy while minimizing adverse effects. Further in-depth investigations, including in vivo studies, are warranted to validate these findings and explore the translational potential of this synergistic approach in clinical settings.</p>","PeriodicalId":15120,"journal":{"name":"Journal of Cancer Prevention","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recommendations for Healthy Lifestyle for Cancer Prevention and Healthy Aging.","authors":"Omer Kucuk, Viraj A Master","doi":"10.15430/JCP.24.018","DOIUrl":"https://doi.org/10.15430/JCP.24.018","url":null,"abstract":"","PeriodicalId":15120,"journal":{"name":"Journal of Cancer Prevention","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Anticancer Activity of Phytochemicals of the Papaya Plant Assessed: A Narrative Review.","authors":"Shachi Patel, Karankumar Rana, Param Arya, Janelle Nelson, Vanesa Hernandez, Victoria Minakova","doi":"10.15430/JCP.24.020","DOIUrl":"https://doi.org/10.15430/JCP.24.020","url":null,"abstract":"<p><p>Cancer remains to be a pervasive disease as traditional treatments have plateaued in efficacy. Anticancer research continues to grow in an effort to find novel preventive and treatment measures for cancers. The papaya plant produces several biologically active phytochemicals, which exhibit anti-inflammatory, antibacterial, and anti-oxidative properties. This review explores studies examining these phytochemicals derived from the papaya plant as a potential chemopreventive agent and a cancer therapeutic. Further studies must be done to establish the papaya plant and its phytochemicals as an alternative to traditional cancer treatments.</p>","PeriodicalId":15120,"journal":{"name":"Journal of Cancer Prevention","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eun-Hye Jeon, So-Young Park, Keon Uk Park, Yun-Han Lee
{"title":"Ribosomal Protein L9 Maintains Stemness of Colorectal Cancer via an ID-1 Dependent Mechanism.","authors":"Eun-Hye Jeon, So-Young Park, Keon Uk Park, Yun-Han Lee","doi":"10.15430/JCP.24.004","DOIUrl":"10.15430/JCP.24.004","url":null,"abstract":"<p><p>The identification of therapeutic target genes that are functionally involved in stemness is crucial to effectively cure patients with metastatic carcinoma. We have previously reported that inhibition of ribosomal protein L9 (RPL9) expression suppresses the growth of colorectal cancer (CRC) cells by inactivating the inhibitor of DNA-binding 1 (ID-1) signaling axis, which is functionally associated with cancer cell survival. In addition to cell proliferation, ID-1 is also involved in the maintenance of cancer stemness. Thus, we aimed in this study to investigate whether the function of RPL9 could correlate with CRC stem cell-like properties. Here, we demonstrated that siRNA silencing of RPL9 reduced the invasiveness and migrative capabilities of HT29 and HCT116 parental cell populations and the capacity for sphere formation in the HT29 parental cell population. CD133<sup>+</sup> cancer stem cells (CSCs) were then separated from CD133<sup>-</sup> cancer cells of the HT29 parental cell culture and treated with RPL9-specific siRNAs to verify the effects of RPL9 targeting on stemness. As a result, knockdown of RPL9 significantly suppressed the proliferative potential of CD133<sup>+</sup> colorectal CSCs, accompanied by a reduction in CD133, ID-1, and p-IκBα levels. In line with these molecular alterations, targeting RPL9 inhibited the invasion, migration, and sphere-forming capacity of CD133<sup>+</sup> HT29 CSCs. Taken together, these findings suggest that RPL9 promotes CRC stemness via ID-1 and that RPL9 could be a potential therapeutic target for both primary CRC treatment and the prevention of metastasis and/or recurrence.</p>","PeriodicalId":15120,"journal":{"name":"Journal of Cancer Prevention","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yonghoon Choi, Nayoung Kim, Chin-Hee Song, Seulgi Kim, Dong Ho Lee
{"title":"The Effect of A2 Milk on Gastrointestinal Symptoms in Comparison to A1/A2 Milk: A Single-center, Randomized, Double-blind, Cross-over Study.","authors":"Yonghoon Choi, Nayoung Kim, Chin-Hee Song, Seulgi Kim, Dong Ho Lee","doi":"10.15430/JCP.24.007","DOIUrl":"10.15430/JCP.24.007","url":null,"abstract":"<p><p>β-Casein, a major protein in cow's milk, is divided into the A1 and A2 type variants. Digestion of A1 β-casein yields the peptide β-casomorphin-7 which could cause gastrointestinal (GI) discomfort but A2 milk containing only A2 β-casein might be more beneficial than A1/A2 (regular) milk. The aim of this study was to evaluate the differences in GI discomfort after ingestion of A2 milk and A1/A2 milk. A randomized, double-blind, cross-over human trial was performed with 40 subjects who experienced GI discomfort following milk consumption. For each intervention period, either A2 milk first (A2→A1/A2) or A1/A2 milk was first consumed for 2 weeks (A1/A2→A2) following a 2-week washout period. GI symptom rating scale (GSRS) scores, questionnaire for digestive symptoms, and laboratory tests including fecal calprotectin were evaluated. For symptom analysis, generalized estimating equations gamma model was used. A2 milk increased bloating (<i>P</i> = 0.041) and loose stools (<i>P</i> = 0.026) compared to A1/A2 milk in GSRS. However, A2 milk caused less abdominal pain (<i>P</i> = 0.050), fecal urgency (<i>P</i> < 0.001) and borborygmus (<i>P</i> = 0.007) compared to A1/A2 milk in questionnaire for digestive symptoms. In addition, fecal calprotectin also decreased or less increased after consumption of A2 milk compared to A1/A2 milk (<i>P</i> = 0.030), and this change was more pronounced in males (<i>P</i> = 0.005) than in females. There were no significant adverse reactions during the trial. A2 milk alleviated digestive discomfort in Koreans following A2 milk consumption (ClinicalTrials.gov NCT06252636 and CRIS KCT0009301).</p>","PeriodicalId":15120,"journal":{"name":"Journal of Cancer Prevention","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Elevated N1-Acetylspermidine Levels in Doxorubicin-treated MCF-7 Cancer Cells: Histone Deacetylase 10 Inhibition with an N1-Acetylspermidine Mimetic.","authors":"Ajay Kumar Raj, Kiran Bharat Lokhande, Kratika Khunteta, Sachin Chakradhar Sarode, Nilesh Kumar Sharma","doi":"10.15430/JCP.24.002","DOIUrl":"10.15430/JCP.24.002","url":null,"abstract":"<p><p>Cancer drug resistance is associated with metabolic adaptation. Cancer cells have been shown to implicate acetylated polyamines in adaptations during cell death. However, exploring the mimetic of acetylated polyamines as a potential anticancer drug is lacking. We performed intracellular metabolite profiling of human breast cancer MCF-7 cells treated with doxorubicin (DOX), a well known anticancer drug. A novel and in-house vertical tube gel electrophoresis assisted procedure followed by LC-HRMS analysis was employed to detect acetylated polyamines such as N1-acetylspermidine. We designed a mimetic N1-acetylspermidine (MINAS) which is a known substrate of histone deacetylase 10 (HDAC10). Molecular docking and molecular dynamics (MDs) simulations were used to evaluate the inhibitory potential of MINAS against HDAC10. The inhibitory potential and the ADMET profile of MINAS were compared to a known HDAC10 inhibitor Tubastatin A. N1-acetylspermidine, an acetylated form of polyamine, was detected intracellularly in MCF-7 cells treated with DOX over DMSO-treated MCF-7 cells. We designed and curated MINAS (PubChem CID 162679241). Molecular docking and MD simulations suggested the strong and comparable inhibitory potential of MINAS (-8.2 kcal/mol) to Tubastatin A (-8.4 kcal/mol). MINAS and Tubastatin A share similar binding sites on HDAC10, including Ser138, Ser140, Tyr183, and Cys184. Additionally, MINAS has a better ADMET profile compared to Tubastatin A, with a high MRTD value and lower toxicity. In conclusion, the data show that N1-acetylspermidine levels rise during DOX-induced breast cancer cell death. Additionally, MINAS, an N1-acetylspermidine mimetic compound, could be investigated as a potential anticancer drug when combined with chemotherapy like DOX.</p>","PeriodicalId":15120,"journal":{"name":"Journal of Cancer Prevention","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Choi, N. Kim, R. Nam, Jae Young Jang, Eun Hye Kim, SungChan Ha, Kisung Kang, Wonseok Lee, C. Shin, D. H. Lee
{"title":"Sex Difference in the Effect of Bifidobacterium longum on Repeated Water Avoidance Stress-induced Gut Dysbiosis in Wistar Rats","authors":"S. Choi, N. Kim, R. Nam, Jae Young Jang, Eun Hye Kim, SungChan Ha, Kisung Kang, Wonseok Lee, C. Shin, D. H. Lee","doi":"10.15430/JCP.23.042","DOIUrl":"https://doi.org/10.15430/JCP.23.042","url":null,"abstract":"Dysbiosis in gut microbiota is known to contribute to development of irritable bowel syndrome. We tried to investigate the effect of Bifidobacterium longum on repeated water avoidance stress (WAS) in a Wistar rat model. The three groups (no-stress, WAS, and WAS with B. longum) of rats were allocated to sham or WAS for 1 hour daily for 10 days, and B. longum was administered through gavage for 10 days. Fecal pellet numbers were counted at the end of each 1-hour session of WAS. After 10 days of repeated WAS, the rats were eutanized, and the feces were collected. WAS increased fecal pellet output (FPO) significantly in both sexes (P < 0.001), while the female B. longum group showed significantly decreased FPO (P = 0.005). However, there was no consistent change of myeloperoxidase activity and mRNA expression of interleukin-1β and TNF-α. Mast cell infiltration at colonic submucosa increased in the female WAS group (P = 0.016). In terms of fecal microbiota, the repeated WAS groups in both sexes showed different beta-diversity compared to control and WAS with B. longum groups. WAS-induced mast cell infiltration was reduced by the administration of B. longum in female rats. Moreover, administration of B. longum relieved WAS-caused dysbiosis, especially in female rats. In conclusion, B. longum was beneficial for WAS-induced stress in rats, especially in females.","PeriodicalId":15120,"journal":{"name":"Journal of Cancer Prevention","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140366233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alessandra Ferraresi, Suyanee Thongchot, C. Isidoro
{"title":"Resveratrol Promotes Self-digestion to Put Cancer to Sleep","authors":"Alessandra Ferraresi, Suyanee Thongchot, C. Isidoro","doi":"10.15430/JCP.24.001","DOIUrl":"https://doi.org/10.15430/JCP.24.001","url":null,"abstract":"Resveratrol, a natural polyphenol present in a variety of food stuff, has been shown to exert preventive and curative anticancer activity in several in vitro and in vivo models. Such chemopreventive/anticancer activity has been linked to biochemical and epigenetic modifications of multiple pathways involved in carcinogenesis and metastasization. In this commentary, we focus on the recent work done in our laboratory showing that resveratrol has potential to prevent and cure cancer by promoting epigenetic-mediated autophagy-dependent tumor dormancy, an effect associated with re-education of the cancer-associated fibroblasts and reduced production of inflammatory cytokines in the tumor microenvironment. The clinical translation of the current knowledge on resveratrol anticancer activity is also discussed.","PeriodicalId":15120,"journal":{"name":"Journal of Cancer Prevention","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140365010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Efficacy of Bacillus Calmette-Guérin in Cancer Prevention and Its Putative Mechanisms","authors":"Sakshi Gupta, Saurabh Yadav, Pawan Kumar","doi":"10.15430/JCP.23.036","DOIUrl":"https://doi.org/10.15430/JCP.23.036","url":null,"abstract":"Bacillus Calmette-Guérin (BCG) is an attenuated strain of Mycobacterium bovis. Although it was developed as a prophylactic vaccine against tuberculosis (TB), researchers have also evaluated it for preventing cancer development or progression. These studies were inspired by the available data regarding the protective effects of microbial infection against cancers and an inverse relationship between TB and cancer mortality. Initial studies demonstrated the efficacy of BCG in preventing leukemia, melanoma and a few other cancers. However, mixed results were observed in later studies. Importantly, these studies have led to the successful use of BCG in the tertiary prevention of non-muscle invasive bladder cancer, wherein BCG therapy has been found to be more effective than chemotherapy. Moreover, in a recently published 60-year follow-up study, childhood BCG vaccination has been found to significantly prevent lung cancer development. In the present manuscript, we reviewed the studies evaluating the efficacy of BCG in cancer prevention and discussed its putative mechanisms. Also, we sought to explain the mixed results of BCG efficacy in preventing different cancers.","PeriodicalId":15120,"journal":{"name":"Journal of Cancer Prevention","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140367847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Potent Suppression of Prostate Cancer Cell Growth and Eradication of Cancer Stem Cells by CD44-targeted Nanoliposome-quercetin Nanoparticles.","authors":"Kader Turkekul, Suat Erdogan","doi":"10.15430/JCP.2023.28.4.160","DOIUrl":"10.15430/JCP.2023.28.4.160","url":null,"abstract":"<p><p>The bioavailability of quercetin, a natural compound, is hindered by low solubility, limited absorption, and restricted systemic availability. Therefore, encapsulating it in biocompatible nanoparticles presents a promising solution. This study aimed to target prostate cancer stem cells (CSCs) overexpressing CD44+ receptors as well as cancer cells, employing quercetin-loaded hyaluronic acid-modified nanoliposomes (LP-Quer-HA). Synthesized via a green ethanol injection method, these nanoliposomes had an average diameter of 134 nm and an impressive loading efficiency of 96.9%. Human prostate cancer cells were treated with either 10 μM of free quercetin or the same concentration delivered by LP-Quer-HA for 72 hours. Free quercetin reduced androgen-resistant PC3 cell viability by 16%, while LP-Quer-HA significantly increased cell death to 60%. It induced apoptosis, upregulating cytochrome <i>c</i>, Bax, caspases 3 and 8, and downregulating survivin and Bcl-2 expression. Compared to free quercetin, LP-Quer-HA upregulated E-cadherin expression while inhibiting cell migration and reducing the expression of fibronectin, N-cadherin, and MMP9. Treatment of PC3 cell tumor spheroids with LP-Quer-HA decreased the number of CD44 cells and expression of CD44, Oct3/4 and Wnt. Moreover, LP-Quer-HA inhibited p-ERK expression while increasing p38/MAPK and NF-κB protein expression. In androgen-sensitive LNCaP cells, LP-Quer-HA efficacy was notable, reducing cell viability from 10% to 52% compared to free quercetin. Utilizing HA-modified nanoliposomes as a quercetin delivery system enhanced its potency at lower concentrations, reducing the CD44+ cell population and effectively impeding prostate cancer cell proliferation and migration. These findings underscore the potential of quercetin-loaded cationic nanoliposomes as a robust therapeutic approach.</p>","PeriodicalId":15120,"journal":{"name":"Journal of Cancer Prevention","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10774486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139417115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}