Philippine E-Journals

Ampalaya (Momordica charantia) and Bayabas (Psidium Guajava) Extracts’ Synergistic Effect on Immortalized Lung Tumor Spheroids (Gl001) Verified in Rt-Pcr and In Silico Modelling

Dominic Karl M. Bolinas | Mary Nicole I. Grecia | Rozel B. Razal | Michael Sigfrid S. Reyes | Francisco M. Heralde Iii

 

Abstract:

In the Philippines, lung cancer is the leading cause of cancer-related deaths in males and the fourth among females. Thus, there is a need for the development of accessible and effective treatments for the disease. Momordica charantia and Psidium guajava have been found to be cytotoxic to A549 lung cancer cells, but the potential of these natural products as a source of anti-cancer bioactive components remain untapped. This study aimed to determine the synergistic effects of M. charantia and P. guajava extracts on spheroidal cultures of GL001 lung cancer cells. Through the hanging drop method, the study was able to generate spheroidal GL001cells, which provided a more appropriate representation of a tumor microenvironment in a Filipino patient-derived lung cancer cell. Furthermore, RT-qPCR analysis revealed that combinatorial extracts treatment induced upregulation of CASP8, a gene involved in Bid cleavage essential in apoptosis activation, and downregulation of MDM2, a gene involved in p53 degradation promoting tumorigenesis. This suggested that the anticancer activity of the combined extracts is through promoting apoptosis and cell cycle arrest. Verification with the in silico molecular docking analysis showed that metabolites found in ampalaya and bayabas may synergistically act by binding to specific sites in CASP8 and MDM2 protein. In particular, the synergistic binding of certain ampalaya and bayabas metabolites to CASP8 potentially stabilizes Bid-CASP8 interaction and promotes apoptosis. On the other hand, the synergistic effect of certain ampalaya and bayabas compounds on MDM2 led to either a decreased p53-MDM2 binding or a potential stabilizing effect. Both scenarios possibly disrupt p53-MDM2 interaction, preventing p53 degradation and thereby promoting cell cycle arrest. Overall, this study showed through gene expression and molecular docking analysis that M. charantia and P. guajava have synergistic anticancer effects on lung cancer cells.