Identification of Anticancer Proteins from the Medicinal Mushroom Ref.No.SSTCRC2546
1. Introduction
In 2022, around 20 million new cancer cases were recorded, accompanied by 9.7 million deaths. Statistically, about one in every five individuals will be afflicted by cancer during their lifespan. Thanks to the progress in early detection methods and the improvement of treatment quality, the survival rates of cancer patients have significantly increased. Nevertheless, the severe side - effects of chemotherapy and the problem of drug resistance still emphasize the urgent need to explore diverse natural sources of anticancer agents.
Proteins and peptides have emerged as crucial natural bioactive substances with great anticancer potential. Recent research has pinpointed over 2,800 proteins as potential cancer drug targets. Some of these have already obtained FDA approval, which clearly demonstrates the vast prospects for the development of protein - based therapies. Compared with small - molecule drugs, proteins have distinct advantages, which has led to their rapid acceptance in the pharmaceutical industry. Protein - based therapies provide a larger binding surface area, enabling the targeting of a wider variety of protein targets. They make it possible to carry out molecular - targeted therapies that can selectively eliminate tumor cells while sparing healthy cells. Promising cancer treatment approaches, such as monoclonal antibodies, exosomal proteins, immune checkpoint inhibitors, drug nanocarriers, and drug delivery systems, have exhibited remarkable effectiveness in both in - vitro and in - vivo experiments.
The Tiger Sawgill mushroom, Lentinus tigrinus (Bull.) Fr., belongs to the Polyporaceae family and is a well - known culinary - medicinal mushroom. It is renowned for its high nutritional value and various pharmaceutical benefits. Similar to other members of the Polyporaceae family, L. tigrinus is abundant in bioactive compounds, including polysaccharides and proteins. These compounds have antioxidant, antibacterial, and anticancer properties. Previous research has suggested that specific protein fractions from L. tigrinus could potentially be powerful anticancer agents. Therefore, further research is needed to isolate and identify the active proteins or peptides within this mushroom.
2. Research Progress
Our research team has concentrated on an Iranian domesticated strain of L. tigrinus that grows efficiently on artificial substrates. We have demonstrated the anticancer activity of L. tigrinus proteins, evaluated the in vivo toxicity and nutritional value of its extracts, and identified its antibacterial properties. Additionally, we investigated the biosynthesis of silver nanoparticles from L. tigrinus extracts and their antibacterial effects, along with the efficacy of these nanoparticles against food - borne pathogens (manuscript in progress).
Our findings on the proposed project are as follows:
-Crude soluble proteins from L. tigrinus (37 - 57 kDa) show anti - proliferative effects at doses below 1000 μg/mL against MCF - 7 and PC - 3 cancer cells.
-These proteins mainly induce cytotoxicity through apoptosis.
-Initially, we isolated fractions of crude soluble proteins using Amicon Ultrafiltration and then conducted anti - proliferative tests on each fraction.
-Further purification and identification of active single fractions are required.
3. Cooperation required
We require financial support for the first five steps. Moreover, we're looking for technical and equipment - related collaboration for the third step.
First, we'll prepare a crude soluble protein fraction from L. tigrinus by using ammonium sulfate precipitation. After that, we'll test this fraction to see its impact on MCF - 7 and PC - 3 cancer cells.
Once the functionality of the protein fraction from the first step is confirmed, we'll use Ion Exchange Chromatography and Gel Filtration Chromatography to obtain highly purified proteins. We'll separate the fractions according to their size and charge.
Next, we'll use LC - MS/MS to identify the selected fractions.
To understand how the fractions induce apoptosis, we'll measure the expression of apoptosis - related proteins through western blot analysis. We'll also use flow cytometry to figure out if a rise in apoptosis is linked to cell cycle arrest.
Finally, if it's suitable, we'll carry out animal testing on the chosen protein fraction.
4. Benefits
The project aims to produce at least one novel anticancer protein-based lead compound for clinical studies, contributing valuable insights into natural lead compounds that could effectively treat breast and prostate cancers.
5. Outputs
The project is expected to achieve following outcomes:
Production and patent of at least one novel anticancer protein-based lead compound to be utilized for further clinical studies
Publication of at least one paper in Q1 journals