B lymphoma is one of the common malignant tumors in the blood system, and chemotherapy is the main treatment for B lymphoma. Commonly used clinical drugs include cyclophosphamide, doxorubicin, vincristine, etc. Chemotherapy can effectively improve the survival rate and prognosis of lymphoma patients, but it still has drawbacks such as high toxicity, high side effects, and susceptibility to drug resistance. Finding safe and low toxicity effective drugs from natural products is a research hotspot in the field of anti-tumor. Researchers have isolated and identified natural compounds with anti lymphoma activity from traditional Chinese medicine derived from plants, while exploring their molecular mechanisms of action. For example, flavonoids such as myricetin and baicalein were isolated from red cardamom and Scutellaria baicalensis. It has been verified that the two compounds exert anti lymphoma effects by targeting the Bruton tyrosine kinase (BTK) and PI3K/AKT signaling pathways, respectively. Garcinia mangostana L., commonly known as mountain bamboo, inverted twisted seeds, etc., is known as the “Queen of Fruits”. Mangkhut fruit shells contain active ingredients such as flavonoids, xanthones, anthocyanins, and proanthocyanidins. In some Southeast Asian regions, they are often used as traditional medicines to treat diseases such as diarrhea, dysentery, and infections. α – mangostin (α – Ma) is an anthraquinone compound with various biological activities, and is one of the main active ingredients in the shell of mangosteen fruit. Studies have shown that α – Ma has potential anti-cancer properties, and has inhibitory activity on gastric cancer, breast cancer, liver cancer, glioblastoma, etc. However, the proliferative inhibitory effect and molecular mechanism of α – Ma on B lymphoma have not been reported yet. Based on this, this study takes human B lymphoma Ramos cells as the research object, observes the effect of α – Ma on Ramos cell proliferation and apoptosis, aims to explore the inhibitory effect of α – Ma on B lymphoma proliferation and its potential molecular mechanism, provide new insights into the anti-tumor activity of α – Ma, and provide theoretical basis for the modification and clinical application of α – Ma based analogs.

 

The unmodified compounds isolated and extracted from natural products have the advantages of multi-target, high safety, and wide availability, demonstrating good advantages in the treatment of tumors. According to statistics, about 60% of existing anti-tumor drugs are natural products or derived from natural products such as paclitaxel and vincristine. Alpha Ma originates from the natural product mangosteen and has been reported to exert anti-tumor effects through various mechanisms. Alpha Ma induces apoptosis in chondrosarcoma cells through the JNK and AKT pathways; Inducing apoptosis of oral cancer cells through the ERK and p38 pathways; Inhibition of breast cancer proliferation through JNK and p38 pathways; Promote the chemical sensitivity of gastric cancer cells through autophagy. In this study, we first discovered the inhibitory effect of α – Ma on the proliferation of B lymphoma Ramos cells. α – Ma inhibits the proliferation of lymphoma Ramos cells in a drug concentration – and time-dependent manner.

Excessive levels of ROS can cause oxidative damage to the body’s DNA and abnormal protein expression, thereby inducing cell apoptosis. P38MAPK is an important member of the MAPK family, and its activation plays a crucial role in the induction of cancer cell apoptosis by various anti-tumor drugs. Research has found that ROS can phosphorylate and activate p38MAPK, thereby inducing the translocation of Bcl-2 family member Bax from the cytoplasm to the outer mitochondrial membrane. The translocation of Bax to the mitochondrial membrane can expand the permeability pore, alter the proton gradient inside and outside the mitochondria, reduce the mitochondrial transmembrane potential, and release pro apoptotic substances (such as AIF and Cyt-c). After being released into the cytoplasm, Cyt-c interacts with the apoptotic enzyme activating factor (Apaf-1) and forms an apoptotic complex with the assistance of ATP and dATP. The apoptotic complex recruits and activates pro-caspase-9, which further activates caspase-3/7, initiates the caspase cascade reaction, cleaves substrates such as PARP, and ultimately induces cell apoptosis. As another member of the Bcl-2 family, Bim promotes Bax activation through both direct binding and competitive binding. Our research results found that α – Ma can increase ROS levels in Ramos cells, reduce MMP, and upregulate the expression of p-p38, Bax, and Bim, activate caspase-3/9 and PARP, and induce apoptosis in Ramos cells.

Based on the above results, we speculate that the possible mechanism by which α – Ma inhibits the proliferation of lymphoma Ramos cells is the activation of ROS/p38 MAPK/Bax cascade reaction by α – Ma, which induces apoptosis in B lymphoma cells. The study elucidated the anti B lymphoma activity and possible mechanism of α – Ma, providing new ideas for the development of anti-tumor drugs based on α – Ma.