Autophagy as one of the most important strategies for the treatment of tuberculosis; Mini-review | ||
Reviews in Clinical Medicine | ||
مقاله 1، دوره 6، شماره 4، بهمن 2019، صفحه 135-139 اصل مقاله (374.3 K) | ||
نوع مقاله: Review | ||
شناسه دیجیتال (DOI): 10.22038/rcm.2019.14176 | ||
نویسندگان | ||
Masoud Youssefi1؛ Majid Eslami2؛ Mohsen Karbalaei3؛ Masoud Keikha* 4؛ Kiarash Ghazvini5 | ||
1Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. | ||
2Department of Microbiology and Virology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran | ||
3Department of Microbiology and Virology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran | ||
4Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran | ||
5Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran | ||
چکیده | ||
Cancer is defined as uncontrolled cell division, which could spread or invade various tissues. There are more than 200 types of cancer, including breast, skin, lung, colon, and prostate cancer, and lymphoma, the symptoms and indications of which vary depending on the type of tissues. Cancer has several treatments with different applications. For instance, chemotherapy, radiation therapy, surgery or their combination are common treatment modalities for cancer. However, a complete cure for cancer has not been achieved yet. On the other hand, novel drugs for cancer treatment are not efficient due to the ability of cancer cells to develop resistance against chemotherapeutic agents. Recently, natural compounds have been reported to improve the efficiency of cancer treatment. Polyunsaturated fatty acids (PUFAs) are natural compounds that could be used as dietary supplements in cancer patients. PUFAs are classified into two main categories, including n-3 and n-6 PUFAs. According to the literature, n-3 PUFAs exert protective effects against cancer through the induction of apoptotic pathways and suppressing cell proliferation, while n-6 PUFAs cause tumor formation by inducing cell growth and proliferation. Using PUFAs in combination with chemotherapeutic agents is considered to be an effective approach to the treatment of cancer patients through increasing cancer cell death. This review aimed to discuss the interactive effects of the structure and function of PUFAs on cancer and cell processes through various signaling pathways. | ||
کلیدواژهها | ||
Autophagy؛ Mycobacterium tuberculosis؛ Treatment؛ Tuberculosis | ||
اصل مقاله | ||
Introduction Mycobacterium tuberculosis (Mtb) is a common cause of death due to infectious diseases across the world. According to the report of the World Health Organization (WHO) in 2017, approximately 10 million new cases of Mtb infection have been recorded, including 5.8 million males, 3.2 million females, and one million children, among which 464,633 cases have been reported to be simultaneously infected with HIV-1. Literature review Mtb effectively employs several strategies to escape the immune system. Therefore, the key to battling TB would be to consider and investigate the molecular mechanisms that may complicate the pathogenesis of Mtb (8). Autophagy is one of the mechanisms of programmed cell death, which occurs in order to maintain normal homeostasis, cellular starvation, adenosine triphosphate (ATP) supply, aging, stress response, and cancer and infectious particles in eukaryotic cells (14). In general, three elements are involved in the autophagy process, including autophagy-related genes (Atgs), autophagosome vesicles interacting with organelles (e.g., mitochondria and endoplasmic reticulum/Golgi apparatus), and lysosomes (15). The most prominent ATGs include ULK1 (Atg1), Beclin-1 (Atg6), PI3PK, hvP34, p62, NBR1, NDP52, LC3 (Atg8; containing the LC3I solution and LC3II lipid form and expressed in three isoforms of LC3A, LC3B, and LC3C), GABARAP, GABARAPL1, and GABARAPL2. LC3II is considered to be the most important autophagy marker, which is produced through the action of Atg3 from LC3I (12, 16). In addition, Beclin-1 and Atg5 play a key role in the regulation of signaling pathways and formation of autophagosomes, while p62 and NDP52 are often expressed as autophagy receptors in the cell cytoplasm (16). According to the literature, the autophagy process is induced and enhanced owing to the degradation of latent TB bacilli in macrophages after isoniazid and pyrazinamide treatment, leading to the release of Mtb antigens and response to ROS and NADPH oxidase (19). In a study in this regard, Gutier et al. demonstrated that the starvation of Mtb-infected macrophages and simultaneous rapamycin treatment increased the interactions between Mtb, Beclin-1, and LC3, thereby inducing autophagy. Furthermore, the mentioned study indicated that IFN-γ could improve the clearance of Mtb from the body via the immunity-related GTPase family M protein 1 signaling pathway through stimulating autophagy (20). Moreover, ATP, damage-associated molecular patterns, vitamin D, and ROS could stimulate and increase autophagy, while IL-1β, IL-10, mycobacterial cell wall compounds (especially phosphatidylinositol ManLAM, ESAT-6, and CFP-10) could restrain and dysregulate autophagy (21). It is speculated that provoking autophagy pathways is an effective anti-TB strategy, which may lead to the development of anti-TB drugs with a new mode of action. In this regard, findings have demonstrated that rapamycin and pyrazinamide treatment could enhance the autophagy pathway (22, 23). In addition, the administration of the antipsychotic drugs that increase and stimulate calcium pumps and metformin through the activation of AMPKs (mTOR inhibitors) could ultimately stimulate and increase autophagy, thereby improving TB control (Table 1) (23, 24). Some of the proteins belonging to the autophagy pathway (especially p62) are also known as neo-antimicrobial peptides owing to their central role against TB and could be synthesized and commercialized as pharmaceutical compounds (25). Conclusion Considering the emergence of high-resistance bacterial strains against common antibiotics and ineffectiveness of TB vaccines (e.g., BCG) in the prevention and treatment of the disease, eradication of TB does not seem to be possible. Therefore, the emphasis lays on the prevention of TB, and the use of immunity-based methods has been highlighted in this regard. Cellular immune responses play a pivotal role against TB, such as the shift to the Th1 response and production of IFN-γ, which leads to the phagocytosis and degradation of Mtb or switching to Th1/Th17, which results in LTBI. Furthermore, the shifts toward Th2/Th22 lead to the production of IL-10, IL-4, IL-13, and CTLA-4, causing the impairment of the cellular immune system and TB re-activation. Interestingly, several of these mechanisms (particularly the signaling pathways of PI3P and PI3K-hVps34) are associated with autophagy development. Acknowledgements Conflict of Interest | ||
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