PRODUCTION OF ANTINEOPLASTIC DRUGS FROM SOIL MICROORGANISMS

As number of cancer patients increasing, the number of chemotherapy treatments are also increasing. This analysis aims to provide a cutting-edge outline of the antineoplastic medications extracted from streptomyces. Streptomyces are the main source of antibiotic production. Antineoplastic medications moderate the pace of tumor development and postpone metastasis. The utilization and performance of the methods are discussed, with focus on the antineoplastic drugs. Streptomyces produces compounds and crude extracts which shows cytostatic reaction across different human cell lines like for breast carcinoma (MCF-7, MDA-MB-231 cell lines), (HepG2 cell lines) hepatic carcinoma, (DU 145 cell lines) prostate cancer and more.

Microbial-derived antineoplastic drugs from-Soil environment

Vancomycinand methicillin
Senthil Kumar et al [8] Isolation Of Antineoplastic Drugs: Plant Derived Antineoplastic Agents: Plants are the main source of highly efficient traditional cancer treatments. Vinca alkaloids, vinblastine, and vincristine, both isolated from Madagascar periwinkle, were the first agents used in clinical trials. these are mostly useful for treating carcinoma breast and leukaemia. [9] Microbial Derived Antineoplastic Agents: Many of best anticancer drugs come from microbes which are used to battle against other cancer cells. The function of microbial symbionts in the development of biologically effective specialised metabolites has been the subject of recent research. Only some studies have found the real producers of specialised metabolites of interest so far [10].

From soil microbes:
To date, microorganisms isolated from soil produces antibiotics which can kill other pathogenic microorganisms. The antineoplastic agents isolated from soil often shows more effect towards cancer cells. [11] The anthracyclines family, doxorubicin and daunorubicin, is one of the most well-known drugs derived from Streptomyces. These medications could take action at different levels to advance apoptosis of malignant growth cells [12].

From Marine Microbes:
Apart from sponges, algae, and corals, marine bacteria and fungi are wellknown to create specialised metabolites with complex and various chemical structures, which can be used to develop new drugs. Secondary metabolites can available in prokaryotes and eukaryotes, including unicellular bacteria (e.g., Bacillus spp. and Pseudomonas spp.), eukaryotic fungi (e.g., Penicillium spp. and Aspergillus spp.), filamentous actinomyces, and filamentous actinomyces (e.g., Streptomyces spp) [13].
In laboratory mice affected with COLO 205 tumours, it was also shown that combining griseofulvin with the antineoplastic agent nocodazole enhanced the results of nocodazole and stopped tumour extension in vivo. [21].

Bacteria:
Staphylococcal superantigens-like (SSL) are a sort of bacterial protein framed by Staphylococcus aureus and equipped for confining few eukaryotic receptors in malignant growth cells. SSL10 connects with CXCR4, a GPCR found in T-ALL lymphoma and cervical carcinoma cells in people. CXCL12 is the most well-known ligand for CXCR4, yet SSL10 movement hindered the chemotactic reaction of HeLa (cervical carcinoma) cells to this ligand. [22] Some bacterial proteins are similarly candidate therapeutic experts for harmful development treatment. This is the circumstance of the amino destructive adulterating compound arginine deiminase of Mycoplasma arginini (Ma-ADI), a tumor advancement inhibitor and perhaps a medicinal expert for the treatment of in vitro and in vivo tumors. for instance, hepatocellular carcinoma, melanoma, leukemia, renal cell carcinoma and prostate threat [23].

Actinobacteria:Streptomyces
Many microorganisms have been studied for producing anti-cancer leads or compounds. The anti-cancer activity of these natural, microbial compounds is capable of inducing apoptosis, regulate functions of the immune system and inhibit the proliferation of the cells. Actinobacteria is one of the largest taxonomic groups, with a wide range of species. It has been known as a primary source for the extraction of natural and bioactive products, like anticancer agents and a variety of other auxiliary metabolites [24,25,26]. Streptomyces is a highly recognized representative of the class of Actinobacteria. In fact, 80% of the natural products from this class are extracted from the Streptomyces genus. Screening potentially anti-cancerous and antineoplastic compounds from Streptomyces that are mangrove derived is the most initial step [27,28]. Studies consisting of experiments have shown that Streptomyces in the mangrove areas demonstrated a certain level of cytotoxic activity that works against cancerous cell lines in humans.For this, it is important that pure and raw extracts of Streptomyces species are isolated [29].
Novel compounds that have antineoplastic potential and properties can be extracted from Streptomycetes that are mangrove derived. Two major compounds, namely, azalomycin F5a and azalomycin F4a 2-ethylcrude extracts [30] have been derived from Streptomyces wherein, both these compounds exhibit extremely high levels of cytotoxicity against cancer of the colon. Also, compounds like indolocarbazoles and streptocarbazoles A and B have been extracted from the Streptomyces species, exhibiting impressive amounts of cytotoxic effects against cancers in humans like Leukemia, HeLa and lung cancer cells [30]. An in-depth analysis has also revealed that one of these 1231 compounds can successfully cause an arrest in the cell cycle in humans, facilitating, antineoplastic property. A significant observation has been made in which the Streptomyces' isolated extract composed of ethyl acetate has demonstrated potential cytotoxicity against two cell lines responsible for breast cancer. A specific fraction of the Streptomyces extract is also capable of causing arrest in cell division cycle in the Gap1 and Gap2 phases, controlling cell proliferation and induces apoptosis that is mitochondria mediated [31]. Savini et al [39] AnticancerousAvtivity: Other than the MTT assay,the SRB (Sulforhodamine B) method can also be used that estimates the total content of protein that is present in the cells and hence, the total number of cells that are viable in the soil microorganisms along with the level of cellular protein present in them can be measured that gives an idea about the cytotoxicity. [40] A colorimetric assay known as the CCK-8 assay is also employed for measuring the viability of cells in vitro for the purpose of proliferation and cytotoxicity experimentation.

1232
Another critical technique called as metagenomics is widely being employed for identifying microorganisms that belong to different environments and have been uncultivable for prolonged periods of time. In such a technique, DNA belonging to the microbes is isolated from an environment sample that has been chosen. The sequence of DNA then obtained will represent the microorganism that is present in the sample [41]. The process of extraction involves the screening for bioactivity performed for raw or crude extracts belonging to Streptomyces. It is followed by the purification process and then finally the partial characterization that is done using methods like IR spectra (infrared spectra) and UV absorption (ultra-violet absorption). For accurate and successful extraction, it is important that conditions developed for culturing are appropriately optimized. This optimization of the conditions for culture is to be done based on the recommendations provided by the "International Streptomyces Project". Post optimization of culture conditions, the isolate has to be identified using comparative properties. The extract then prepared from the cell culture broth containing the isolate can be analyzed using the above-mentioned assays or array techniques like HPLC diode technique [42]. There is very limited amount of knowledge as to the mechanisms that are involved for successful antineoplastic or anti-cancerous activities in cells and furthermore, living beings.

Insilico-Docking Studies:
Concentrates from common items, particularly microorganisms, have demonstrated to be a significant wellspring of different atoms in a few medication disclosures endeavors, prompting the revelation of various significant medications. The disclosure of different bioactive particles has come about because of the ID of microbial strains with promising natural exercises and the refinement of the bio-atoms answerable for the exercises. The MTT (3-[4, 5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) method was utilized to assess the in vitro cytotoxicity of the extracellular and intracellular focuses on HeLa cells. MTT testing was utilized to screen the most perplexing concentrates on MCF-7 cells. Two incredibly powerful thinks were picked for Hoechst 33342 staining and cell cycle examination to see whether the compound interceded apoptosis on HeLa cells, in view of the aftereffects of in vitro anticancer examinations of both extracellular and intracellular concentrates [43]. Utilizing the web-based programming apparatuses PEP-FOLD and iCn3D, the 3D development of the peptide NMANF2 was illustrated. The objective receptors of M. tuberculosis, cellular breakdown in the lungs (A540), and colon disease (HT-29) cells were recovered in 3D structure from the RCSB PDB. Hex 8.0.0 docking writing computer programs was utilized to examine and imagine in silico sub-atomic docking among ligands and proteins from M. tuberculosis and disease cell lines (A540 and HT-29) [44,45].
Discovery of Novel Compounds with Anticancer/Cytotoxic Activity from Mangrove-Derived Streptomyces sp

Conclusion:-
Natural products, such as those used in cancer treatment, have a significant impact on enhancing and improving human wellbeing. Streptomyces are promising producers of anti-cancerous property compounds and are reported from various habitats such as soil, plant parts and even from air [98]. In this review, the secondary bioactive metabolites extracted from Streptomyces have been highlighted to possess enormous potential as antineoplastic pharmaceuticals along with addressing the urgent need of expanding the current research done in this field, involving approaches of several types like the identification and purification of targeted compounds along with in depth study of these microorganisms present in the soil followed by the analysis of active strains consisting of the biosynthetic category of gene clusters.