Review
Oncology
Octavio Daniel Reyes-Hernandez, Gabriela Figueroa-Gonzalez, Laura Itzel Quintas-Granados, Stephany Celeste Gutierrez-Ruiz, Hector Hernandez-Parra, Alejandra Romero-Montero, Maria Luisa Del Prado-Audelo, Sergio Alberto Bernal-Chavez, Hernan Cortes, Sheila I. Pena-Corona, Lashyn Kiyekbayeva, Dilek Arslan Atessahin, Tamar Goloshvili, Gerardo Leyva-Gomez, Javad Sharifi-Rad
Summary: The dietary compounds I3C and DIM found in cruciferous vegetables have shown potential in cancer prevention. Clinical and preclinical trials have demonstrated their antioxidant, cancer preventive, and anti-tumor activities. However, the precise mechanism by which they exert these effects is still not fully understood.
CANCER CELL INTERNATIONAL
(2023)
Article
Biochemical Research Methods
Alexander P. Lakeev, Elena A. Yanovskaya, Daria V. Tsuran, Olga S. Bryushinina, Natalia Yu. Abdrashitova, Yulia G. Zyuz'kova, Vladimir V. Udut, Vsevolod I. Kiselev, Igor N. Kuznetsov
Summary: This study established an HPLC-MS/MS method for quantifying DIM in human plasma. The method showed good sensitivity, accuracy, and precision, allowing for DIM quantification in the concentration range of 5-500 ng/ml. 4-Methoxy-1-methylindole was used as an internal standard during sample extraction and analysis.
BIOMEDICAL CHROMATOGRAPHY
(2022)
Article
Infectious Diseases
Yifat Baruch, Karina Golberg, Qun Sun, Karina Yew-Hoong Gin, Robert S. Marks, Ariel Kushmaro
Summary: This study tested the effect of a natural compound called 3,3'-Diindolylmethane (DIM) on the biofilm of the oral bacterium Streptococcus mutans. The results showed that DIM was able to reduce the formation of S. mutans biofilm and decrease its durability under acidic conditions. This suggests that DIM has potential in reducing biofilm formation and preventing dental caries.
Article
Pharmacology & Pharmacy
Monica L. Vermillion Maier, Lisbeth K. Siddens, Sandra L. Uesugi, Jaewoo Choi, Scott W. Leonard, Jamie M. Pennington, Susan C. Tilton, Jordan N. Smith, Emily Ho, H. H. Sherry Chow, Bach D. Nguyen, Siva K. Kolluri, David E. Williams
Summary: 3,3'-Diindolylmethane (DIM) is a phytochemical found in cruciferous vegetables that has been studied as a cancer chemopreventive agent. Previous pharmacokinetic studies did not detect metabolites of DIM in plasma or urine after oral dosing, but this new study found multiple metabolites in human samples, indicating the need for further research on the pharmacological properties of DIM metabolites.
DRUG METABOLISM AND DISPOSITION
(2021)
Review
Nutrition & Dietetics
David E. Williams
Summary: Studies have shown the effectiveness of I3C and DIM in cancer prevention, especially in pre-clinical models, and they have shown promise in clinical trials. The focus of research has been on understanding the mechanisms of action of DIM in preventing breast and prostate cancer, as well as comparing the impact of dietary intake of cruciferous vegetables containing I3C/DIM versus supplementation.
FRONTIERS IN NUTRITION
(2021)
Article
Pharmacology & Pharmacy
Karina Golberg, Victor Markus, Bat-el Kagan, Sigalit Barzanizan, Karin Yaniv, Kerem Terali, Esti Kramarsky-Winter, Robert S. Marks, Ariel Kushmaro
Summary: Antimicrobial resistance, particularly antibacterial resistance, is a major global health problem. Current treatments for bacterial diseases are ineffective due to protective and resistant biofilm structures. This study investigates the anti-virulence activity of 3,3'-diindolylmethane (DIM), a phytochemical, and finds that it has anti-biofilm activity against major Gram-negative pathogens. Combining DIM with an antibiotic enhances its inhibition of biofilm formation. The study also reveals the molecular mechanisms underlying bacterial response to DIM, providing evidence for its potential in attenuating bacterial virulence.
Article
Pharmacology & Pharmacy
Jessica Brandao Reolon, Camila Parcianello Saccol, Barbara Felin Osmari, Daiane Britto de Oliveira, Vinicius Costa Prado, Fernanda Licker Cabral, Lucas Saldanha da Rosa, Giancarlo Cervo Rechia, Daniela Bitencourt Rosa Leal, Leticia Cruz
Summary: This study aimed to develop a bilayer film for topical melanoma therapy by incorporating nanocapsules containing 3,3 '-diindolylmethane (DIM) with antitumor activity. The nanofilms showed appropriate behavior for cutaneous application and controlled DIM release profile, and increased the permeation of DIM into the epidermis. The combination of karaya and gellan gum in the bilayer films demonstrated potential in the topical treatment of melanoma.
Article
Microbiology
Yong-Guy Kim, Jin-Hyung Lee, Sunyoung Park, Jintae Lee
Summary: The study investigated the antibacterial and antibiofilm activities of 20 indoles against Cutibacterium acnes, a bacterium that inhabits human skin and is implicated in acne vulgaris formation. The results showed that indole-3-carbinol and 3,3'-diindolylmethane significantly inhibited biofilm formation by C. acnes. Furthermore, 3,3'-diindolylmethane successfully inhibited multispecies biofilm formation by C. acnes, Staphylococcus aureus, and Candida albicans. Transcriptional analyses showed that 3,3'-diindolylmethane inhibited the expressions of several biofilm-related genes in C. acnes and inhibited hyphal formation and cell aggregation by C. albicans. These findings suggest that 3,3'-diindolylmethane could be a potential treatment for acne vulgaris and biofilm-associated infections.
MICROBIOLOGY SPECTRUM
(2022)
Article
Pharmacology & Pharmacy
Monica L. Vermillion Maier, Lisbeth K. Siddens, Jamie M. Pennington, Sandra L. Uesugi, Susan C. Tilton, Emily A. Vertel, Kim A. Anderson, Lane G. Tidwell, Ted J. Ognibene, Kenneth W. Turteltaub, Jordan N. Smith, David E. Williams
Summary: Using UPLC-AMS, we found significant first-pass metabolism of [14C]-BaP in humans following oral micro-dosing. This study examined the effect of dietary supplementation with Brussels sprouts or DIM on plasma levels of [14C]-BaP and metabolites. Results showed that both interventions significantly reduced plasma levels of [14C]-BaP and its metabolites, indicating slower absorption and accelerated clearance for certain metabolites.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yang Ye, Xue Li, Zhihua Wang, Fen Ye, Wenrong Xu, Rongzhu Lu, Haijun Shen, Shuhan Miao
Summary: The natural compound 3,3'-Diindolylmethane (DIM) inhibits proliferation and induces apoptosis and autophagy in gastric cancer cells by activating the STIM1-mediated Store-operated calcium entry (SOCE) pathway. Inhibition of SOCE attenuates DIM-induced effects on apoptosis and autophagy, suggesting SOCE as a potential therapeutic target in gastric cancer. Further research is warranted to explore combination chemotherapy strategies targeting SOCE for clinical applications.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Oncology
Fenfen Xiang, Zhaowei Zhu, Mengzhe Zhang, Jie Wang, Zixi Chen, Xiaoxiao Li, Tao Zhang, Qing Gu, Rong Wu, Xiangdong Kang
Summary: DNMT1-mediated hypermethylation of KLF4 promoter leads to downregulation of KLF4 in breast cancer. The level of KLF4 is correlated with the sensitivity of MCF-7 and T47D cells to PTX. DIM could enhance the antitumor efficacy of PTX on MCF-7 and T47D cells by regulating DNMT1 and KLF4.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xuanhe Fu, Mingkai Xu, Zhixiong Yu, Wu Gu, Zhichun Zhang, Bowen Zhang, Xiujuan Wang, Zhencheng Su, Chenggang Zhang
Summary: This study reveals that cell stiffness is a resistance factor to cytotoxic T cell-induced apoptosis in ovarian cancer, and altering cancer cell stiffness can enhance the antitumor effect of superantigen ST-4.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Organic
Rui-Ying Zhang, Feng Jin, Xiao-Guang Bao, Hai-Yan Li, Xiao-Ping Xu, Shun-Jun Ji
Summary: A cascade reaction mediated by N-bromosuccinimide involving the cyclization/oxygen-migration/ring-contraction process of 3-(beta, beta-diaryl) indolylethanol was disclosed, leading to efficient synthesis of a variety of spiro 3,3'-cyclopropyl oxindole derivatives under mild reaction conditions. A possible mechanism was suggested based on intermediate isolation and computational studies.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Hao Tang, Kunpeng Qin, Anquan Wang, Shuang Li, Sheng Fang, Weilu Gao, Ming Lu, Wei Huang, Hui Zhang, Zongsheng Yin
Summary: This study found that DIM can inhibit chondrocyte apoptosis and ECM degradation induced by LPS by regulating the PI3K/AKT/mTOR-autophagy axis, thus delaying the progression of osteoarthritis.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Hui Shi, Yaoxiang Sun, Hongru Ruan, Cheng Ji, Jiahui Zhang, Peipei Wu, Linli Li, Chihan Huang, Yuanwang Jia, Xu Zhang, Wenrong Xu, Jiajia Jiang, Hui Qian
Summary: The study found that the anti-cancer drug DIM at therapeutic concentrations upregulated the expression of tumor-related factors in GC-MSCs and promoted the proliferation, invasion, and migration of gastric cancer cells, leading to tumor growth. This mechanism provides a new insight into anti-cancer drug resistance and suggests the need to adjust the chemotherapy regimen to minimize the side effects of drugs on targeted TME cells.
FRONTIERS IN ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Bryan Latrell Holloman, Mitzi Nagarkatti, Prakash Nagarkatti
Summary: Chronic inflammation is believed to be the underlying cause of various diseases, including cardiovascular and neurological diseases, while cannabinoids are thought to suppress inflammation through multiple pathways, including regulating gene epigenetic modulation, which helps inhibit inflammation and discover new therapeutic approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Piper A. Robida, Alena P. Chumanevich, Alexa Orr Gandy, John W. Fuseler, Prakash Nagarkatti, Mitzi Nagarkatti, Carole A. Oskeritzian
Summary: The study suggests that in the pre-lesional phase of atopic dermatitis, elevated levels of ceramides lead to increased apoptosis of skin cells, which may be influenced by activated mast cells. The results reveal that the MC/Cer axis may be an essential pathogenic feature in the development of atopic dermatitis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Guoshuai Cai, Mulong Du, Yohan Bosse, Helmut Albrecht, Fei Qin, Xizhi Luo, Xiao Michelle Androulakis, Chao Cheng, Mitzi Nagarkatti, Prakash Nagarkatti, David C. Christiani, Michael L. Whitfield, Christopher Amos, Feifei Xiao
Summary: The study found differential trends in the expression of DC-SIGN gene in the lungs and blood of COVID-19 patients, with an increase in immature DCs in severe cases, but an increase in pDCs in mild cases. In severe cases, although DCs stimulate innate immune responses, they fail to specifically present SARS-CoV-2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Punnag Saha, Peter T. Skidmore, LaRinda A. Holland, Ayan Mondal, Dipro Bose, Ratanesh K. Seth, Kimberly Sullivan, Patricia A. Janulewicz, Ronnie Horner, Nancy Klimas, Mitzi Nagarkatti, Prakash Nagarkatti, Efrem S. Lim, Saurabh Chatterjee
Summary: The study demonstrates that treatment with andrographolide can significantly improve Gut-Brain axis-related pathology in a mouse model of GWI, potentially providing a much-needed therapeutic avenue for this condition.
Review
Biochemistry & Molecular Biology
Alkeiver S. Cannon, Prakash S. Nagarkatti, Mitzi Nagarkatti
Summary: Activation of Aryl Hydrocarbon Receptor (AhR) was previously excluded from therapeutic approaches due to potential toxic effects and induction of Cyp1a1 enzyme. However, it is now understood that AhR activation functions as an environmental sensor and immunomodulator, attenuating inflammation. This review summarizes research on AhR and its role in regulating inflammation, highlighting its potential in immune response modulation for inflammatory and autoimmune diseases. The opportunities and challenges of developing AhR-based therapies to suppress inflammation are also discussed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Nicholas Dopkins, Wurood Hantoosh Neameh, Alina Hall, Yunjia Lai, Alex Rutkovsky, Alexa Orr Gandy, Kun Lu, Prakash S. Nagarkatti, Mitzi Nagarkatti
Summary: The study found that acute exposure to TCDD results in immediate dysregulation in the circulating and intestinal metabolome of mice, which affects host immunity and broad-scale metabolic processes. These metabolic changes can serve as biomarkers for TCDD toxicity and early detection of individual exposure.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Muthanna Sultan, Kiesha Wilson, Osama A. Abdulla, Philip Brandon Busbee, Alina Hall, Taylor Carter, Narendra Singh, Saurabh Chatterjee, Prakash Nagarkatti, Mitzi Nagarkatti
Summary: The study showed that treatment with anandamide (AEA) attenuated SEB-mediated ARDS by inducing AMPs, tight junction proteins, and short-chain fatty acids (SCFAs), which stabilized the gut-lung microbial axis, suppressed inflammation, and prevented dysbiosis in both the lungs and the gut.
Article
Immunology
Xiaoming Yang, Alex C. Rutkovsky, Juhua Zhou, Yin Zhong, Julian Reese, Timothy Schnell, Helmut Albrecht, William B. Owens, Prakash S. Nagarkatti, Mitzi Nagarkatti
Summary: The study investigates alterations in epigenetic pathways and gene expression profiles in hospitalized COVID-19 patients. It reveals significant upregulation of inflammation-related genes and alterations in coagulation-related genes in COVID-19 patients. The study also identifies potential therapeutic targets and biomarkers for COVID-19 disease, including dexamethasone and TEC family kinases.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Kathryn Miranda, William Becker, Philip B. Busbee, Nicholas Dopkins, Osama A. Abdulla, Yin Zhong, Jiajia Zhang, Mitzi Nagarkatti, Prakash S. Nagarkatti
Summary: This study investigates the role of CB1 in immune and non-immune cells during diet-induced obesity (DIO). The results show that CB1 in non-immune cells is necessary for induction of DIO, while CB1 in immune cells exacerbates DIO and leads to other metabolic abnormalities.